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Can exercise prevent cognitive decline in patients with early Parkinson’s disease?
, new research suggests. Investigators found that patients with Parkinson’s disease who were APOE epsilon4 carriers had greater cognitive decline compared with non-APOE epsilon4 carriers, but the findings also revealed higher physical activity appeared to slow cognitive decline in this higher risk group.
“The main finding of the current study is that higher physical activity was related to slower APOE epsilon4-associated cognitive decline in patients with early Parkinson’s disease, which was shown to be robust in sensitivity analyses,” wrote the researchers, led by Ryul Kim, MD, Inha University Hospital, Incheon, Korea.
The study was published online March 31 in Neurology.
Unclear mechanism
The APOE epsilon4 allele is known to be a “major risk factor” for Alzheimer’s disease, but “accumulating evidence shows that this allele also has a potential role in cognitive impairment in Parkinson’s disease,” the authors noted.
Previous research shows physical activity has beneficial effects in patients with Parkinson’s disease, but the mechanisms underlying these effects are “not well understood.” Additional data suggest physical activity modifies the APOE epsilon4 effect on the development and progression of Alzheimer’s disease.
“These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE [epsilon4] and cognition in Parkinson’s disease,” but no studies have yet reported on this interaction in patients with Parkinson’s disease, the authors noted.
To investigate, they drew on data from the Parkinson’s Progression Markers Initiative (PPMI) – a cohort study conducted to identify Parkinson’s disease progression markers.
The current analysis included 173 patients recently diagnosed with Parkinson’s disease but not yet treated for the condition. The cohort’s mean age was 63.3 ± 10.0 years, age of Parkinson’s disease onset was 59.4 ± 10.0 years, and 68% were male. Of these participants, 46 were APOE epsilon4 carriers.
Dopamine transporter (DAT) activity was assessed using imaging at enrollment and again at years 2 and 4. Cognitive function was assessed at years 2, 3, and 4 using the Montreal Cognitive Assessment (MoCA) test.
Protective effect
Although APOE epsilon4 carriers tended to be younger than noncarriers, the age of Parkinson’s disease onset did not differ between the 2 groups, and there were also no significant differences between the groups in demographic and clinical variables.
There were larger declines in MoCA scores in the APOE epsilon4 carriers versus the noncarriers (0.21 ± 1.40 and 0.08 ± 1.15 respectively).
The APOE epsilon4 allele was associated with a “steeper” rate of cognitive decline, compared with the non-APOE epsilon4 allele (estimate −1.33 [95% confidence interval, −2.12 to −0.47, P = .002).
There was a significant interaction of physical activity, APOE epsilon4, and time: Higher physical activity was associated with slower APOE epsilon4-related cognitive decline (estimate 0.007 [0.003 to 0.011, P = .001).
However, the researchers found no significant main effects of the APOE epsilon4 allele or physical activity on the change in the MoCA score.
“Considering that dopaminergic treatment may affect cognitive function, particularly in the early stage of Parkinson’s disease, we additionally included the levodopa daily equivalent dose (LEDD) and its interaction with time as covariates in the model,” the investigators noted.
They found that the interactive association between physical activity and the APOE epsilon4 allele on cognitive decline remained significant, even when participants who had normal cognitive performance at year 2 were included in the study population or when LEDD variables were included as covariates in the model.
Both high- and low-intensity exercise were significantly associated with slower APOE epsilon4-related cognitive decline.
There was no significant interaction between physical activity and APOE epsilon4 with changes in striatal DAT activities.
“Increased physical activity attenuated APOE epsilon4-related vulnerability to early cognitive decline in patients with Parkinson’s disease,” the authors noted, adding that the effect “did not appear to be mediated by striatal dopamine activity.”
They hypothesized that physical activity may “offer a greater protective effect” on cerebral amyloid accumulation in APOE epsilon4 carriers. It is also possible that physical activity will counteract the negative impact of the APOE epsilon4 allele through improved brain mechanism and decreased neuroinflammation.
‘The next blockbuster drug’
Commenting on the study in an interview, Bastiaan R. Bloem, MD, PhD, director of the center of expertise for Parkinson & movement disorders, Radboud University Medical Center, Nijmegen, Netherlands, said exercise might be seen as “the next blockbuster drug.”
Dr. Bloem, who was not involved in the study, noted there is “quite robust evidence now that exercise acts as symptomatic therapy, like a drug, alleviating sleep [disturbances], depression, constipation, and motor symptoms.”
The study “sheds new light on the idea of exercise as not only alleviating symptoms but actually as a potential disease modifier,” said Dr. Bloem, whose research has focused on the beneficial effects of a rigorous exercise program, combined with tablet-based gamificaton and a reward system in stabilizing motor symptoms in patients with Parkinson’s disease over time.
“The reward system created additional motivation for the patients with Parkinson’s disease who often experience depression and apathy that interfere with motivation,” he said.
The current study has important take-home messages for practicing clinicians. “Physicians should encourage exercise in patients, and patients should also take the lead themselves,” Dr. Bloem said. “It doesn’t matter what type of exercise you do, but it should have an aerobic component, should be safe so the patient doesn’t fall down, should have enough intensity to cause the patient to pant, and should be individualized and enjoyable so the patients stick to it,” he emphasized.
Dr. Bloem noted that yoga and mindfulness are also helpful. “If we’ve learned anything from the COVID-19 crisis, it’s that chronic stress is deleterious to all of us and particularly bad for people with PD, because you need dopamine to be able to handle stress, and the lack of dopamine in people with PD makes them deteriorate faster.”
The study was supported by a research grant of National Research Foundation by the Ministry of Science and ICT (MSIT) in Korea. The authors and Dr. Bloem have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Investigators found that patients with Parkinson’s disease who were APOE epsilon4 carriers had greater cognitive decline compared with non-APOE epsilon4 carriers, but the findings also revealed higher physical activity appeared to slow cognitive decline in this higher risk group.
“The main finding of the current study is that higher physical activity was related to slower APOE epsilon4-associated cognitive decline in patients with early Parkinson’s disease, which was shown to be robust in sensitivity analyses,” wrote the researchers, led by Ryul Kim, MD, Inha University Hospital, Incheon, Korea.
The study was published online March 31 in Neurology.
Unclear mechanism
The APOE epsilon4 allele is known to be a “major risk factor” for Alzheimer’s disease, but “accumulating evidence shows that this allele also has a potential role in cognitive impairment in Parkinson’s disease,” the authors noted.
Previous research shows physical activity has beneficial effects in patients with Parkinson’s disease, but the mechanisms underlying these effects are “not well understood.” Additional data suggest physical activity modifies the APOE epsilon4 effect on the development and progression of Alzheimer’s disease.
“These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE [epsilon4] and cognition in Parkinson’s disease,” but no studies have yet reported on this interaction in patients with Parkinson’s disease, the authors noted.
To investigate, they drew on data from the Parkinson’s Progression Markers Initiative (PPMI) – a cohort study conducted to identify Parkinson’s disease progression markers.
The current analysis included 173 patients recently diagnosed with Parkinson’s disease but not yet treated for the condition. The cohort’s mean age was 63.3 ± 10.0 years, age of Parkinson’s disease onset was 59.4 ± 10.0 years, and 68% were male. Of these participants, 46 were APOE epsilon4 carriers.
Dopamine transporter (DAT) activity was assessed using imaging at enrollment and again at years 2 and 4. Cognitive function was assessed at years 2, 3, and 4 using the Montreal Cognitive Assessment (MoCA) test.
Protective effect
Although APOE epsilon4 carriers tended to be younger than noncarriers, the age of Parkinson’s disease onset did not differ between the 2 groups, and there were also no significant differences between the groups in demographic and clinical variables.
There were larger declines in MoCA scores in the APOE epsilon4 carriers versus the noncarriers (0.21 ± 1.40 and 0.08 ± 1.15 respectively).
The APOE epsilon4 allele was associated with a “steeper” rate of cognitive decline, compared with the non-APOE epsilon4 allele (estimate −1.33 [95% confidence interval, −2.12 to −0.47, P = .002).
There was a significant interaction of physical activity, APOE epsilon4, and time: Higher physical activity was associated with slower APOE epsilon4-related cognitive decline (estimate 0.007 [0.003 to 0.011, P = .001).
However, the researchers found no significant main effects of the APOE epsilon4 allele or physical activity on the change in the MoCA score.
“Considering that dopaminergic treatment may affect cognitive function, particularly in the early stage of Parkinson’s disease, we additionally included the levodopa daily equivalent dose (LEDD) and its interaction with time as covariates in the model,” the investigators noted.
They found that the interactive association between physical activity and the APOE epsilon4 allele on cognitive decline remained significant, even when participants who had normal cognitive performance at year 2 were included in the study population or when LEDD variables were included as covariates in the model.
Both high- and low-intensity exercise were significantly associated with slower APOE epsilon4-related cognitive decline.
There was no significant interaction between physical activity and APOE epsilon4 with changes in striatal DAT activities.
“Increased physical activity attenuated APOE epsilon4-related vulnerability to early cognitive decline in patients with Parkinson’s disease,” the authors noted, adding that the effect “did not appear to be mediated by striatal dopamine activity.”
They hypothesized that physical activity may “offer a greater protective effect” on cerebral amyloid accumulation in APOE epsilon4 carriers. It is also possible that physical activity will counteract the negative impact of the APOE epsilon4 allele through improved brain mechanism and decreased neuroinflammation.
‘The next blockbuster drug’
Commenting on the study in an interview, Bastiaan R. Bloem, MD, PhD, director of the center of expertise for Parkinson & movement disorders, Radboud University Medical Center, Nijmegen, Netherlands, said exercise might be seen as “the next blockbuster drug.”
Dr. Bloem, who was not involved in the study, noted there is “quite robust evidence now that exercise acts as symptomatic therapy, like a drug, alleviating sleep [disturbances], depression, constipation, and motor symptoms.”
The study “sheds new light on the idea of exercise as not only alleviating symptoms but actually as a potential disease modifier,” said Dr. Bloem, whose research has focused on the beneficial effects of a rigorous exercise program, combined with tablet-based gamificaton and a reward system in stabilizing motor symptoms in patients with Parkinson’s disease over time.
“The reward system created additional motivation for the patients with Parkinson’s disease who often experience depression and apathy that interfere with motivation,” he said.
The current study has important take-home messages for practicing clinicians. “Physicians should encourage exercise in patients, and patients should also take the lead themselves,” Dr. Bloem said. “It doesn’t matter what type of exercise you do, but it should have an aerobic component, should be safe so the patient doesn’t fall down, should have enough intensity to cause the patient to pant, and should be individualized and enjoyable so the patients stick to it,” he emphasized.
Dr. Bloem noted that yoga and mindfulness are also helpful. “If we’ve learned anything from the COVID-19 crisis, it’s that chronic stress is deleterious to all of us and particularly bad for people with PD, because you need dopamine to be able to handle stress, and the lack of dopamine in people with PD makes them deteriorate faster.”
The study was supported by a research grant of National Research Foundation by the Ministry of Science and ICT (MSIT) in Korea. The authors and Dr. Bloem have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. Investigators found that patients with Parkinson’s disease who were APOE epsilon4 carriers had greater cognitive decline compared with non-APOE epsilon4 carriers, but the findings also revealed higher physical activity appeared to slow cognitive decline in this higher risk group.
“The main finding of the current study is that higher physical activity was related to slower APOE epsilon4-associated cognitive decline in patients with early Parkinson’s disease, which was shown to be robust in sensitivity analyses,” wrote the researchers, led by Ryul Kim, MD, Inha University Hospital, Incheon, Korea.
The study was published online March 31 in Neurology.
Unclear mechanism
The APOE epsilon4 allele is known to be a “major risk factor” for Alzheimer’s disease, but “accumulating evidence shows that this allele also has a potential role in cognitive impairment in Parkinson’s disease,” the authors noted.
Previous research shows physical activity has beneficial effects in patients with Parkinson’s disease, but the mechanisms underlying these effects are “not well understood.” Additional data suggest physical activity modifies the APOE epsilon4 effect on the development and progression of Alzheimer’s disease.
“These observations led us to hypothesize that physical activity also plays a role in modulating the association between APOE [epsilon4] and cognition in Parkinson’s disease,” but no studies have yet reported on this interaction in patients with Parkinson’s disease, the authors noted.
To investigate, they drew on data from the Parkinson’s Progression Markers Initiative (PPMI) – a cohort study conducted to identify Parkinson’s disease progression markers.
The current analysis included 173 patients recently diagnosed with Parkinson’s disease but not yet treated for the condition. The cohort’s mean age was 63.3 ± 10.0 years, age of Parkinson’s disease onset was 59.4 ± 10.0 years, and 68% were male. Of these participants, 46 were APOE epsilon4 carriers.
Dopamine transporter (DAT) activity was assessed using imaging at enrollment and again at years 2 and 4. Cognitive function was assessed at years 2, 3, and 4 using the Montreal Cognitive Assessment (MoCA) test.
Protective effect
Although APOE epsilon4 carriers tended to be younger than noncarriers, the age of Parkinson’s disease onset did not differ between the 2 groups, and there were also no significant differences between the groups in demographic and clinical variables.
There were larger declines in MoCA scores in the APOE epsilon4 carriers versus the noncarriers (0.21 ± 1.40 and 0.08 ± 1.15 respectively).
The APOE epsilon4 allele was associated with a “steeper” rate of cognitive decline, compared with the non-APOE epsilon4 allele (estimate −1.33 [95% confidence interval, −2.12 to −0.47, P = .002).
There was a significant interaction of physical activity, APOE epsilon4, and time: Higher physical activity was associated with slower APOE epsilon4-related cognitive decline (estimate 0.007 [0.003 to 0.011, P = .001).
However, the researchers found no significant main effects of the APOE epsilon4 allele or physical activity on the change in the MoCA score.
“Considering that dopaminergic treatment may affect cognitive function, particularly in the early stage of Parkinson’s disease, we additionally included the levodopa daily equivalent dose (LEDD) and its interaction with time as covariates in the model,” the investigators noted.
They found that the interactive association between physical activity and the APOE epsilon4 allele on cognitive decline remained significant, even when participants who had normal cognitive performance at year 2 were included in the study population or when LEDD variables were included as covariates in the model.
Both high- and low-intensity exercise were significantly associated with slower APOE epsilon4-related cognitive decline.
There was no significant interaction between physical activity and APOE epsilon4 with changes in striatal DAT activities.
“Increased physical activity attenuated APOE epsilon4-related vulnerability to early cognitive decline in patients with Parkinson’s disease,” the authors noted, adding that the effect “did not appear to be mediated by striatal dopamine activity.”
They hypothesized that physical activity may “offer a greater protective effect” on cerebral amyloid accumulation in APOE epsilon4 carriers. It is also possible that physical activity will counteract the negative impact of the APOE epsilon4 allele through improved brain mechanism and decreased neuroinflammation.
‘The next blockbuster drug’
Commenting on the study in an interview, Bastiaan R. Bloem, MD, PhD, director of the center of expertise for Parkinson & movement disorders, Radboud University Medical Center, Nijmegen, Netherlands, said exercise might be seen as “the next blockbuster drug.”
Dr. Bloem, who was not involved in the study, noted there is “quite robust evidence now that exercise acts as symptomatic therapy, like a drug, alleviating sleep [disturbances], depression, constipation, and motor symptoms.”
The study “sheds new light on the idea of exercise as not only alleviating symptoms but actually as a potential disease modifier,” said Dr. Bloem, whose research has focused on the beneficial effects of a rigorous exercise program, combined with tablet-based gamificaton and a reward system in stabilizing motor symptoms in patients with Parkinson’s disease over time.
“The reward system created additional motivation for the patients with Parkinson’s disease who often experience depression and apathy that interfere with motivation,” he said.
The current study has important take-home messages for practicing clinicians. “Physicians should encourage exercise in patients, and patients should also take the lead themselves,” Dr. Bloem said. “It doesn’t matter what type of exercise you do, but it should have an aerobic component, should be safe so the patient doesn’t fall down, should have enough intensity to cause the patient to pant, and should be individualized and enjoyable so the patients stick to it,” he emphasized.
Dr. Bloem noted that yoga and mindfulness are also helpful. “If we’ve learned anything from the COVID-19 crisis, it’s that chronic stress is deleterious to all of us and particularly bad for people with PD, because you need dopamine to be able to handle stress, and the lack of dopamine in people with PD makes them deteriorate faster.”
The study was supported by a research grant of National Research Foundation by the Ministry of Science and ICT (MSIT) in Korea. The authors and Dr. Bloem have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NEUROLOGY
Life after death, and the case of the disappearing digit
It’s alive!!!
Calling all “The Walking Dead” fans! Did you know that, after death, certain cells in the brain can stay active and even become colossal?
Researchers evaluated brain tissue to feign the gene expression during autopsy and death. By doing this, they found that these inflammatory cells, called glial cells, can increase gene expression and “grow and sprout long arm-like appendages for many hours after death.”
According to Dr. Jeffrey Loeb, the study’s senior author, the continued growth after death doesn’t come as a shock since these are the cells that do damage control after certain brain injuries, such as stroke.
Maybe those mindless zombies aren’t so mindless after all. We’re not sure if we should be more scared of a zombie that can think, or a zombie that can’t. We’re sensing a spin-off!
Beam me up, Doc!
In the realm of Star Trek, Dr. Leonard “Bones” McCoy isn’t the only physician who seems to find merit in the adventures of the starship Enterprise.
Pediatric cardiologist Victor Grech, it was reported, has been so influenced by the generational hit that the show made special guest appearances in his medical writing.
The alarm was sounded by a student at Oxford University who had suspicions about more than 100 articles published in Early Human Development. Of the articles eventually withdrawn by the journal’s publisher, Elsevier, 26 were on COVID-19 alone.
Just like a Romulan cloaking device, where the stories once stood Elsevier has left a “withdrawn” statement, making the articles vanish out of thin air.
Along with articles on COVID-19, Dr. Grech’s 48-article series with coauthors on how to write a scientific paper rightfully came into question. Elsevier’s statement on the incident says that the journal’s editorial work flow has been redesigned “to ensure that this will not happen again in the future.”
The number of retracted articles boldly puts Dr. Grech in a lane where few men have gone before.
Something’s wrong, but I can’t put my finger on it
Mixed martial arts is not a sport for the faint of heart. However, we doubt fans who were watching the Khetag Pliev/Devin Goodale fight on April 1 were prepared for the announcement that a search was commencing for a missing finger. Not broken, in case you think that was a misprint. Completely 100% removed from the rest of the hand.
One would think that pinpointing the exact moment when the finger, belonging to Mr. Pliev, was severed would be easy, but the video evidence is unclear, with the best guess being that a kick in the first round broke the finger and a grapple in the second severed it completely. Mr. Pliev was not helpful in clearing up the matter; not only did he fail to immediately notice the fact that his finger had broken or severed, he tried to keep the fight going after the second round when the referee noticed some blood where his left ring finger should have been. He thought he was winning. Unfortunately, the doctor on hand, who was clearly a complete drag, felt differently, ending the fight and awarding it to Mr. Goodale in a technical knockout.
Rest assured, there is a happy ending to this gruesome story. After a frantic search, the missing finger was found deep within Mr. Pliev’s glove and was successfully reattached in a Philadelphia emergency room.
The LOTME team commends Mr. Pliev’s commitment to his craft by wanting to continue the fight, but we respectfully disagree with his assertion that he was winning. We’re fairly confident that body part removal is an automatic loss (pun intended), unless you’re the Black Knight from “Monty Python and the Holy Grail.” Then it’s a draw.
Take two cookies and call me in the morning
The placebo effect is a well-known phenomenon. A pharmacologically inactive treatment can help people if they don’t know it’s pharmacologically inactive. But what if they did know? Would it still work?
That’s what researchers at Beth Israel Deaconess Medical Center in Boston wanted to find out. They divided a cohort of patients with irritable bowel syndrome into three groups. One group got pill bottles containing “open-label placebo,” so the subjects knew they were getting a placebo. The second received bottles labeled “double-blind placebo or peppermint oil.” The third got no pills but followed the rest of the study protocol.
Can you see where this is going? Two-thirds of the open-label placebo group had meaningful improvement of their symptoms, there was no difference in improvement between the two placebo groups, and both did significantly better than the no-pill group.
“If the presumption that deception is necessary for placebos to be effective is false, then many theories about the mechanisms that drive placebo effects may need modification,” investigator Ted J. Kaptchuk said in a written statement.
In other words, this changes everything. Who needs real drugs when anything that a doctor gives to a patient will help? Someone who has trouble swallowing pills can get a milkshake instead. Kid doesn’t like the taste of amoxicillin? Prescribe a slice of therapeutic pizza. Vaccine deniers can get a shot of vitamin C … or bourbon. And just imagine all the good that can be done in this crazy, mixed up world with a batch of chocolate chip cookies.
It’s alive!!!
Calling all “The Walking Dead” fans! Did you know that, after death, certain cells in the brain can stay active and even become colossal?
Researchers evaluated brain tissue to feign the gene expression during autopsy and death. By doing this, they found that these inflammatory cells, called glial cells, can increase gene expression and “grow and sprout long arm-like appendages for many hours after death.”
According to Dr. Jeffrey Loeb, the study’s senior author, the continued growth after death doesn’t come as a shock since these are the cells that do damage control after certain brain injuries, such as stroke.
Maybe those mindless zombies aren’t so mindless after all. We’re not sure if we should be more scared of a zombie that can think, or a zombie that can’t. We’re sensing a spin-off!
Beam me up, Doc!
In the realm of Star Trek, Dr. Leonard “Bones” McCoy isn’t the only physician who seems to find merit in the adventures of the starship Enterprise.
Pediatric cardiologist Victor Grech, it was reported, has been so influenced by the generational hit that the show made special guest appearances in his medical writing.
The alarm was sounded by a student at Oxford University who had suspicions about more than 100 articles published in Early Human Development. Of the articles eventually withdrawn by the journal’s publisher, Elsevier, 26 were on COVID-19 alone.
Just like a Romulan cloaking device, where the stories once stood Elsevier has left a “withdrawn” statement, making the articles vanish out of thin air.
Along with articles on COVID-19, Dr. Grech’s 48-article series with coauthors on how to write a scientific paper rightfully came into question. Elsevier’s statement on the incident says that the journal’s editorial work flow has been redesigned “to ensure that this will not happen again in the future.”
The number of retracted articles boldly puts Dr. Grech in a lane where few men have gone before.
Something’s wrong, but I can’t put my finger on it
Mixed martial arts is not a sport for the faint of heart. However, we doubt fans who were watching the Khetag Pliev/Devin Goodale fight on April 1 were prepared for the announcement that a search was commencing for a missing finger. Not broken, in case you think that was a misprint. Completely 100% removed from the rest of the hand.
One would think that pinpointing the exact moment when the finger, belonging to Mr. Pliev, was severed would be easy, but the video evidence is unclear, with the best guess being that a kick in the first round broke the finger and a grapple in the second severed it completely. Mr. Pliev was not helpful in clearing up the matter; not only did he fail to immediately notice the fact that his finger had broken or severed, he tried to keep the fight going after the second round when the referee noticed some blood where his left ring finger should have been. He thought he was winning. Unfortunately, the doctor on hand, who was clearly a complete drag, felt differently, ending the fight and awarding it to Mr. Goodale in a technical knockout.
Rest assured, there is a happy ending to this gruesome story. After a frantic search, the missing finger was found deep within Mr. Pliev’s glove and was successfully reattached in a Philadelphia emergency room.
The LOTME team commends Mr. Pliev’s commitment to his craft by wanting to continue the fight, but we respectfully disagree with his assertion that he was winning. We’re fairly confident that body part removal is an automatic loss (pun intended), unless you’re the Black Knight from “Monty Python and the Holy Grail.” Then it’s a draw.
Take two cookies and call me in the morning
The placebo effect is a well-known phenomenon. A pharmacologically inactive treatment can help people if they don’t know it’s pharmacologically inactive. But what if they did know? Would it still work?
That’s what researchers at Beth Israel Deaconess Medical Center in Boston wanted to find out. They divided a cohort of patients with irritable bowel syndrome into three groups. One group got pill bottles containing “open-label placebo,” so the subjects knew they were getting a placebo. The second received bottles labeled “double-blind placebo or peppermint oil.” The third got no pills but followed the rest of the study protocol.
Can you see where this is going? Two-thirds of the open-label placebo group had meaningful improvement of their symptoms, there was no difference in improvement between the two placebo groups, and both did significantly better than the no-pill group.
“If the presumption that deception is necessary for placebos to be effective is false, then many theories about the mechanisms that drive placebo effects may need modification,” investigator Ted J. Kaptchuk said in a written statement.
In other words, this changes everything. Who needs real drugs when anything that a doctor gives to a patient will help? Someone who has trouble swallowing pills can get a milkshake instead. Kid doesn’t like the taste of amoxicillin? Prescribe a slice of therapeutic pizza. Vaccine deniers can get a shot of vitamin C … or bourbon. And just imagine all the good that can be done in this crazy, mixed up world with a batch of chocolate chip cookies.
It’s alive!!!
Calling all “The Walking Dead” fans! Did you know that, after death, certain cells in the brain can stay active and even become colossal?
Researchers evaluated brain tissue to feign the gene expression during autopsy and death. By doing this, they found that these inflammatory cells, called glial cells, can increase gene expression and “grow and sprout long arm-like appendages for many hours after death.”
According to Dr. Jeffrey Loeb, the study’s senior author, the continued growth after death doesn’t come as a shock since these are the cells that do damage control after certain brain injuries, such as stroke.
Maybe those mindless zombies aren’t so mindless after all. We’re not sure if we should be more scared of a zombie that can think, or a zombie that can’t. We’re sensing a spin-off!
Beam me up, Doc!
In the realm of Star Trek, Dr. Leonard “Bones” McCoy isn’t the only physician who seems to find merit in the adventures of the starship Enterprise.
Pediatric cardiologist Victor Grech, it was reported, has been so influenced by the generational hit that the show made special guest appearances in his medical writing.
The alarm was sounded by a student at Oxford University who had suspicions about more than 100 articles published in Early Human Development. Of the articles eventually withdrawn by the journal’s publisher, Elsevier, 26 were on COVID-19 alone.
Just like a Romulan cloaking device, where the stories once stood Elsevier has left a “withdrawn” statement, making the articles vanish out of thin air.
Along with articles on COVID-19, Dr. Grech’s 48-article series with coauthors on how to write a scientific paper rightfully came into question. Elsevier’s statement on the incident says that the journal’s editorial work flow has been redesigned “to ensure that this will not happen again in the future.”
The number of retracted articles boldly puts Dr. Grech in a lane where few men have gone before.
Something’s wrong, but I can’t put my finger on it
Mixed martial arts is not a sport for the faint of heart. However, we doubt fans who were watching the Khetag Pliev/Devin Goodale fight on April 1 were prepared for the announcement that a search was commencing for a missing finger. Not broken, in case you think that was a misprint. Completely 100% removed from the rest of the hand.
One would think that pinpointing the exact moment when the finger, belonging to Mr. Pliev, was severed would be easy, but the video evidence is unclear, with the best guess being that a kick in the first round broke the finger and a grapple in the second severed it completely. Mr. Pliev was not helpful in clearing up the matter; not only did he fail to immediately notice the fact that his finger had broken or severed, he tried to keep the fight going after the second round when the referee noticed some blood where his left ring finger should have been. He thought he was winning. Unfortunately, the doctor on hand, who was clearly a complete drag, felt differently, ending the fight and awarding it to Mr. Goodale in a technical knockout.
Rest assured, there is a happy ending to this gruesome story. After a frantic search, the missing finger was found deep within Mr. Pliev’s glove and was successfully reattached in a Philadelphia emergency room.
The LOTME team commends Mr. Pliev’s commitment to his craft by wanting to continue the fight, but we respectfully disagree with his assertion that he was winning. We’re fairly confident that body part removal is an automatic loss (pun intended), unless you’re the Black Knight from “Monty Python and the Holy Grail.” Then it’s a draw.
Take two cookies and call me in the morning
The placebo effect is a well-known phenomenon. A pharmacologically inactive treatment can help people if they don’t know it’s pharmacologically inactive. But what if they did know? Would it still work?
That’s what researchers at Beth Israel Deaconess Medical Center in Boston wanted to find out. They divided a cohort of patients with irritable bowel syndrome into three groups. One group got pill bottles containing “open-label placebo,” so the subjects knew they were getting a placebo. The second received bottles labeled “double-blind placebo or peppermint oil.” The third got no pills but followed the rest of the study protocol.
Can you see where this is going? Two-thirds of the open-label placebo group had meaningful improvement of their symptoms, there was no difference in improvement between the two placebo groups, and both did significantly better than the no-pill group.
“If the presumption that deception is necessary for placebos to be effective is false, then many theories about the mechanisms that drive placebo effects may need modification,” investigator Ted J. Kaptchuk said in a written statement.
In other words, this changes everything. Who needs real drugs when anything that a doctor gives to a patient will help? Someone who has trouble swallowing pills can get a milkshake instead. Kid doesn’t like the taste of amoxicillin? Prescribe a slice of therapeutic pizza. Vaccine deniers can get a shot of vitamin C … or bourbon. And just imagine all the good that can be done in this crazy, mixed up world with a batch of chocolate chip cookies.
‘Beyond a reasonable doubt’: COVID-19 brain health fallout is real, severe
COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.
The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.
“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.
Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.
The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
High rate of neurologic, psychiatric disorders
The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period.
All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.
The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.
The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.
The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.
Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.
“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.
Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
Largest study to date
Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.
There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.
“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.
In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.
Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”
“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”
Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
Need for replication
Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.
“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.
“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.
Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.
“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.
Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
Beyond a reasonable doubt
Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”
Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added.
“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.
“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”
A version of this article first appeared on Medscape.com.
COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.
The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.
“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.
Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.
The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
High rate of neurologic, psychiatric disorders
The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period.
All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.
The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.
The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.
The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.
Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.
“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.
Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
Largest study to date
Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.
There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.
“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.
In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.
Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”
“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”
Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
Need for replication
Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.
“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.
“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.
Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.
“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.
Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
Beyond a reasonable doubt
Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”
Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added.
“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.
“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”
A version of this article first appeared on Medscape.com.
COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.
The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.
“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.
Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.
The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
High rate of neurologic, psychiatric disorders
The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period.
All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.
The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.
The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.
The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.
Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.
“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.
Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
Largest study to date
Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.
There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.
“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.
In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.
Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”
“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”
Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
Need for replication
Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.
“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.
“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.
Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.
“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.
Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
Beyond a reasonable doubt
Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”
Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added.
“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.
“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”
A version of this article first appeared on Medscape.com.
About one in five clinicians considers quitting because of pandemic
a new survey of more than 5,000 clinicians at an academic medical center illustrates.
About one in five people reported considering leaving the workforce because of the challenges of working during the COVID-19 pandemic. In addition, 30% reported they are considering cutting back work hours.
“There are a substantial number of employees and trainees who are experiencing major stress and work disruptions because of the pandemic,” lead author Rebecca K. Delaney, PhD, said in an interview. “It is particularly alarming that people who have spent 5 or more years in training for their specialty are struggling with their work, so much so that they have even considered leaving the workforce or reducing their hours.”
“Being a caregiver adds another layer of difficulty for faculty, staff, and trainees who are trying to manage work and child care,” added Dr. Delaney, a researcher in the department of population health sciences, University of Utah, Salt Lake City.
The study was published online April 2 in JAMA Network Open.
“This looks like an excellent survey,” Carol A Bernstein, MD, said in an interview when asked to comment. “I do not think it provides particularly new information as these challenges in the workplace, especially for women during COVID, have been well documented in the media and the medical literature to date.”
“That said, to the extent that data helps drive solutions, I would hope that information such as this would be considered as strong further evidence that health care systems must pay close attention to the wellbeing of the workforce,” added Dr. Bernstein, professor and vice chair of faculty development and well-being, departments of psychiatry and behavioral sciences and obstetrics and gynecology and women’s health, Montefiore Medical Center/Albert Einstein College of Medicine, New York.
When the pandemic hits home
A total of 42% of the American workforce rapidly transitioned to working from home at the onset of the COVID-19 pandemic. At the same time, many employees had to provide child care and assistance with schoolwork. This placed a burden on many individuals at academic medical centers, and women in particular.
“Women comprise 74.9% of hospital employees, many of whom are essential clinical workers,” the researchers noted. “The extent of the needs and difficulties for these workers during the pandemic remain largely unknown.”
To learn more, Dr. Delaney, senior author Angie Fagerlin, PhD, and their colleagues emailed a Qualtrics survey to 27,700 faculty, staff, and trainees at University of Utah Health. The survey was conducted Aug. 5-20, 2020 as part of a quality improvement initiative. All responses were anonymous.
Survey questions included if, because of the pandemic, people had considered leaving the workforce, considered reducing their hours, or experienced reduced productivity. The researchers also asked about career impacts and potential solutions in terms of “work culture adaptations.”
Respondents with children aged under 18 years also were asked about child care options. Dr. Delaney and colleagues also inquired about race and ethnicity because they hypothesized that employees from underrepresented groups would likely experience the pandemic differently.
The mean age of the 5,951 (21%) faculty, staff, and trainees who completed the survey was 40 years. A majority of respondents were women, reflecting the higher proportion of women within the health system.
A majority (86%) identified as White or European American. About two-thirds of respondents (66%) were staff, 16% were faculty, and 13% were trainees.
COVID-19 career concerns
Overall, 1,061 respondents (21%) “moderately or very seriously” considered leaving the workforce and 1,505 (30%) considered reducing hours. Respondents who were younger, married, a member of an underrepresented racial/ethnic group, and worked in a clinical setting were more likely to consider leaving the workforce.
The survey showed 27% felt their productivity increased whereas 39% believed their productivity decreased.
Of the 2,412 survey participants with children aged 18 years or younger, 66% reported that they did not have child care fully available.
“Failure to address and provide for child care has long been one of the many significant deficits in U.S. health care systems,” said Dr. Bernstein, lead author of a March 2021 report evaluating staff emotional support at Montefiore Medical Center during the pandemic in The Joint Commission Journal on Quality and Patient Safety.
Furthermore, 47% were “moderately or very seriously worried” about COVID-19 impacting their career development.
Women trainees were significantly more likely than male counterparts to consider leaving the workforce and reducing their work hours. Women in a faculty or trainee role were also more likely to worry about COVID-19’s impact on their career, compared with men, and compared with women in staff positions.
“It was disheartening to have our data support the gender and racial/ethnic disparity that has been highlighted in the media during the pandemic,” Dr. Delaney said. “Women and in some cases racial/ethnic groups that are underrepresented in medicine were most likely to consider leaving the workforce, reducing hours, and were worried about their career development.
“It is critical that we strategically address these important disparities,” she said.
Women also are disproportionately affected by burnout, particularly during the pandemic, according to an analysis of Medscape’s Physician Burnout and Suicide Report.
Furthermore, the COVID-19 pandemic has shifted the medical specialties now considered highest risk for burnout: critical care physicians ranked first in the report, followed by rheumatologists and infectious disease specialists.
Potential solutions
“Given the disproportionate impact COVID-19 has on employees of health systems, institutions must find ways to support their employees, both in terms of workplace cultural adaptations and assistance with familial responsibilities,” the researchers noted.
Telecommuting policies, scheduling flexibility, and expanding employee support programs are potential solutions. Institutional policies also could address the educational and direct care needs of employee children.
Limitations of the study include its generalizability beyond employees of University of Utah Health. Also, respondents included a lower proportion of racial and ethnic groups, compared with national figures, “although this is mostly accounted for by the overall low population of such groups in the state of Utah,” the researchers added.
“Our results suggest that respondents were struggling during the COVID-19 pandemic,” the researchers noted. “As a result, even after investing substantial amounts of time in years of training, many were considering leaving the workforce because of stress and caregiving responsibilities related to the pandemic.”
The Jon M. Huntsman Presidential Endowed Chair supported the work with a financial award to Dr. Fagerlin. Dr. Delaney and Dr. Bernstein disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new survey of more than 5,000 clinicians at an academic medical center illustrates.
About one in five people reported considering leaving the workforce because of the challenges of working during the COVID-19 pandemic. In addition, 30% reported they are considering cutting back work hours.
“There are a substantial number of employees and trainees who are experiencing major stress and work disruptions because of the pandemic,” lead author Rebecca K. Delaney, PhD, said in an interview. “It is particularly alarming that people who have spent 5 or more years in training for their specialty are struggling with their work, so much so that they have even considered leaving the workforce or reducing their hours.”
“Being a caregiver adds another layer of difficulty for faculty, staff, and trainees who are trying to manage work and child care,” added Dr. Delaney, a researcher in the department of population health sciences, University of Utah, Salt Lake City.
The study was published online April 2 in JAMA Network Open.
“This looks like an excellent survey,” Carol A Bernstein, MD, said in an interview when asked to comment. “I do not think it provides particularly new information as these challenges in the workplace, especially for women during COVID, have been well documented in the media and the medical literature to date.”
“That said, to the extent that data helps drive solutions, I would hope that information such as this would be considered as strong further evidence that health care systems must pay close attention to the wellbeing of the workforce,” added Dr. Bernstein, professor and vice chair of faculty development and well-being, departments of psychiatry and behavioral sciences and obstetrics and gynecology and women’s health, Montefiore Medical Center/Albert Einstein College of Medicine, New York.
When the pandemic hits home
A total of 42% of the American workforce rapidly transitioned to working from home at the onset of the COVID-19 pandemic. At the same time, many employees had to provide child care and assistance with schoolwork. This placed a burden on many individuals at academic medical centers, and women in particular.
“Women comprise 74.9% of hospital employees, many of whom are essential clinical workers,” the researchers noted. “The extent of the needs and difficulties for these workers during the pandemic remain largely unknown.”
To learn more, Dr. Delaney, senior author Angie Fagerlin, PhD, and their colleagues emailed a Qualtrics survey to 27,700 faculty, staff, and trainees at University of Utah Health. The survey was conducted Aug. 5-20, 2020 as part of a quality improvement initiative. All responses were anonymous.
Survey questions included if, because of the pandemic, people had considered leaving the workforce, considered reducing their hours, or experienced reduced productivity. The researchers also asked about career impacts and potential solutions in terms of “work culture adaptations.”
Respondents with children aged under 18 years also were asked about child care options. Dr. Delaney and colleagues also inquired about race and ethnicity because they hypothesized that employees from underrepresented groups would likely experience the pandemic differently.
The mean age of the 5,951 (21%) faculty, staff, and trainees who completed the survey was 40 years. A majority of respondents were women, reflecting the higher proportion of women within the health system.
A majority (86%) identified as White or European American. About two-thirds of respondents (66%) were staff, 16% were faculty, and 13% were trainees.
COVID-19 career concerns
Overall, 1,061 respondents (21%) “moderately or very seriously” considered leaving the workforce and 1,505 (30%) considered reducing hours. Respondents who were younger, married, a member of an underrepresented racial/ethnic group, and worked in a clinical setting were more likely to consider leaving the workforce.
The survey showed 27% felt their productivity increased whereas 39% believed their productivity decreased.
Of the 2,412 survey participants with children aged 18 years or younger, 66% reported that they did not have child care fully available.
“Failure to address and provide for child care has long been one of the many significant deficits in U.S. health care systems,” said Dr. Bernstein, lead author of a March 2021 report evaluating staff emotional support at Montefiore Medical Center during the pandemic in The Joint Commission Journal on Quality and Patient Safety.
Furthermore, 47% were “moderately or very seriously worried” about COVID-19 impacting their career development.
Women trainees were significantly more likely than male counterparts to consider leaving the workforce and reducing their work hours. Women in a faculty or trainee role were also more likely to worry about COVID-19’s impact on their career, compared with men, and compared with women in staff positions.
“It was disheartening to have our data support the gender and racial/ethnic disparity that has been highlighted in the media during the pandemic,” Dr. Delaney said. “Women and in some cases racial/ethnic groups that are underrepresented in medicine were most likely to consider leaving the workforce, reducing hours, and were worried about their career development.
“It is critical that we strategically address these important disparities,” she said.
Women also are disproportionately affected by burnout, particularly during the pandemic, according to an analysis of Medscape’s Physician Burnout and Suicide Report.
Furthermore, the COVID-19 pandemic has shifted the medical specialties now considered highest risk for burnout: critical care physicians ranked first in the report, followed by rheumatologists and infectious disease specialists.
Potential solutions
“Given the disproportionate impact COVID-19 has on employees of health systems, institutions must find ways to support their employees, both in terms of workplace cultural adaptations and assistance with familial responsibilities,” the researchers noted.
Telecommuting policies, scheduling flexibility, and expanding employee support programs are potential solutions. Institutional policies also could address the educational and direct care needs of employee children.
Limitations of the study include its generalizability beyond employees of University of Utah Health. Also, respondents included a lower proportion of racial and ethnic groups, compared with national figures, “although this is mostly accounted for by the overall low population of such groups in the state of Utah,” the researchers added.
“Our results suggest that respondents were struggling during the COVID-19 pandemic,” the researchers noted. “As a result, even after investing substantial amounts of time in years of training, many were considering leaving the workforce because of stress and caregiving responsibilities related to the pandemic.”
The Jon M. Huntsman Presidential Endowed Chair supported the work with a financial award to Dr. Fagerlin. Dr. Delaney and Dr. Bernstein disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
a new survey of more than 5,000 clinicians at an academic medical center illustrates.
About one in five people reported considering leaving the workforce because of the challenges of working during the COVID-19 pandemic. In addition, 30% reported they are considering cutting back work hours.
“There are a substantial number of employees and trainees who are experiencing major stress and work disruptions because of the pandemic,” lead author Rebecca K. Delaney, PhD, said in an interview. “It is particularly alarming that people who have spent 5 or more years in training for their specialty are struggling with their work, so much so that they have even considered leaving the workforce or reducing their hours.”
“Being a caregiver adds another layer of difficulty for faculty, staff, and trainees who are trying to manage work and child care,” added Dr. Delaney, a researcher in the department of population health sciences, University of Utah, Salt Lake City.
The study was published online April 2 in JAMA Network Open.
“This looks like an excellent survey,” Carol A Bernstein, MD, said in an interview when asked to comment. “I do not think it provides particularly new information as these challenges in the workplace, especially for women during COVID, have been well documented in the media and the medical literature to date.”
“That said, to the extent that data helps drive solutions, I would hope that information such as this would be considered as strong further evidence that health care systems must pay close attention to the wellbeing of the workforce,” added Dr. Bernstein, professor and vice chair of faculty development and well-being, departments of psychiatry and behavioral sciences and obstetrics and gynecology and women’s health, Montefiore Medical Center/Albert Einstein College of Medicine, New York.
When the pandemic hits home
A total of 42% of the American workforce rapidly transitioned to working from home at the onset of the COVID-19 pandemic. At the same time, many employees had to provide child care and assistance with schoolwork. This placed a burden on many individuals at academic medical centers, and women in particular.
“Women comprise 74.9% of hospital employees, many of whom are essential clinical workers,” the researchers noted. “The extent of the needs and difficulties for these workers during the pandemic remain largely unknown.”
To learn more, Dr. Delaney, senior author Angie Fagerlin, PhD, and their colleagues emailed a Qualtrics survey to 27,700 faculty, staff, and trainees at University of Utah Health. The survey was conducted Aug. 5-20, 2020 as part of a quality improvement initiative. All responses were anonymous.
Survey questions included if, because of the pandemic, people had considered leaving the workforce, considered reducing their hours, or experienced reduced productivity. The researchers also asked about career impacts and potential solutions in terms of “work culture adaptations.”
Respondents with children aged under 18 years also were asked about child care options. Dr. Delaney and colleagues also inquired about race and ethnicity because they hypothesized that employees from underrepresented groups would likely experience the pandemic differently.
The mean age of the 5,951 (21%) faculty, staff, and trainees who completed the survey was 40 years. A majority of respondents were women, reflecting the higher proportion of women within the health system.
A majority (86%) identified as White or European American. About two-thirds of respondents (66%) were staff, 16% were faculty, and 13% were trainees.
COVID-19 career concerns
Overall, 1,061 respondents (21%) “moderately or very seriously” considered leaving the workforce and 1,505 (30%) considered reducing hours. Respondents who were younger, married, a member of an underrepresented racial/ethnic group, and worked in a clinical setting were more likely to consider leaving the workforce.
The survey showed 27% felt their productivity increased whereas 39% believed their productivity decreased.
Of the 2,412 survey participants with children aged 18 years or younger, 66% reported that they did not have child care fully available.
“Failure to address and provide for child care has long been one of the many significant deficits in U.S. health care systems,” said Dr. Bernstein, lead author of a March 2021 report evaluating staff emotional support at Montefiore Medical Center during the pandemic in The Joint Commission Journal on Quality and Patient Safety.
Furthermore, 47% were “moderately or very seriously worried” about COVID-19 impacting their career development.
Women trainees were significantly more likely than male counterparts to consider leaving the workforce and reducing their work hours. Women in a faculty or trainee role were also more likely to worry about COVID-19’s impact on their career, compared with men, and compared with women in staff positions.
“It was disheartening to have our data support the gender and racial/ethnic disparity that has been highlighted in the media during the pandemic,” Dr. Delaney said. “Women and in some cases racial/ethnic groups that are underrepresented in medicine were most likely to consider leaving the workforce, reducing hours, and were worried about their career development.
“It is critical that we strategically address these important disparities,” she said.
Women also are disproportionately affected by burnout, particularly during the pandemic, according to an analysis of Medscape’s Physician Burnout and Suicide Report.
Furthermore, the COVID-19 pandemic has shifted the medical specialties now considered highest risk for burnout: critical care physicians ranked first in the report, followed by rheumatologists and infectious disease specialists.
Potential solutions
“Given the disproportionate impact COVID-19 has on employees of health systems, institutions must find ways to support their employees, both in terms of workplace cultural adaptations and assistance with familial responsibilities,” the researchers noted.
Telecommuting policies, scheduling flexibility, and expanding employee support programs are potential solutions. Institutional policies also could address the educational and direct care needs of employee children.
Limitations of the study include its generalizability beyond employees of University of Utah Health. Also, respondents included a lower proportion of racial and ethnic groups, compared with national figures, “although this is mostly accounted for by the overall low population of such groups in the state of Utah,” the researchers added.
“Our results suggest that respondents were struggling during the COVID-19 pandemic,” the researchers noted. “As a result, even after investing substantial amounts of time in years of training, many were considering leaving the workforce because of stress and caregiving responsibilities related to the pandemic.”
The Jon M. Huntsman Presidential Endowed Chair supported the work with a financial award to Dr. Fagerlin. Dr. Delaney and Dr. Bernstein disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Age-related cognitive decline not inevitable?
Investigators found that despite the presence of neuropathologies associated with Alzheimer’s disease (AD), many centenarians maintained high levels of cognitive performance.
“Cognitive decline is not inevitable,” senior author Henne Holstege, PhD, assistant professor, Amsterdam Alzheimer Center and Clinical Genetics, Amsterdam University Medical Center, said in an interview.
“At 100 years or older, high levels of cognitive performance can be maintained for several years, even when individuals are exposed to risk factors associated with cognitive decline,” she said.
The study was published online Jan. 15 in JAMA Network Open.
Escaping cognitive decline
Dr. Holstege said her interest in researching aging and cognitive health was inspired by the “fascinating” story of Hendrikje van Andel-Schipper, who died at age 115 in 2015 “completely cognitively healthy.” Her mother, who died at age 100, also was cognitively intact at the end of her life.
“I wanted to know how it is possible that some people can completely escape all aspects of cognitive decline while reaching extreme ages,” Dr. Holstege said.
To discover the secret to cognitive health in the oldest old, Dr. Holstege initiated the 100-Plus Study, which involved a cohort of healthy centenarians.
The investigators conducted extensive neuropsychological testing and collected blood and fecal samples to examine “the myriad factors that influence physical health, including genetics, neuropathology, blood markers, and the gut microbiome, to explore the molecular and neuropsychologic constellations associated with the escape from cognitive decline.”
The goal of the research was to investigate “to what extent centenarians were able to maintain their cognitive health after study inclusion, and to what extent this was associated with genetic, physical, or neuropathological features,” she said.
The study included 330 centenarians who completed one or more neuropsychological assessments. Neuropathologic studies were available for 44 participants.
To assess baseline cognitive performance, the researchers administered a wide array of neurocognitive tests, as well as the Mini–Mental State Examination, from which mean z scores for cognitive domains were calculated.
Additional factors in the analysis included sex, age, APOE status, cognitive reserve, physical health, and whether participants lived independently.
At autopsy, amyloid-beta (A-beta) level, the level of intracellular accumulation of phosphorylated tau protein in neurofibrillary tangles (NFTs), and the neuritic plaque (NP) load were assessed.
Resilience and cognitive reserve
At baseline, the median age of the centenarians (n = 330, 72.4% women) was 100.5 years (interquartile range, 100.2-101.7). A little over half (56.7%) lived independently, and the majority had good vision (65%) and hearing (56.4%). Most (78.8%) were able to walk independently, and 37.9% had achieved the highest International Standard Classification of Education level of postsecondary education.
The researchers found “varying degrees of neuropathology” in the brains of the 44 donors, including A-beta, NFT, and NPs.
The duration of follow-up in analyzing cognitive trajectories ranged from 0 to 4 years (median, 1.6 years).
Assessments of all cognitive domains showed no decline, with the exception of a “slight” decrement in memory function (beta −.10 SD per year; 95% confidence interval, –.14 to –.05 SD; P < .001).
Cognitive performance was associated with factors of physical health or cognitive reserve, for example, greater independence in performing activities of daily living, as assessed by the Barthel index (beta .37 SD per year; 95% CI, .24-.49; P < .001), or higher educational level (beta .41 SD per year; 95% CI, .29-.53; P < .001).
Despite findings of neuropathologic “hallmarks” of AD post mortem in the brains of the centenarians, these were not associated with cognitive performance or rate of decline.
APOE epsilon-4 or an APOE epsilon-3 alleles also were not significantly associated with cognitive performance or decline, suggesting that the “effects of APOE alleles are exerted before the age of 100 years,” the authors noted.
“Our findings suggest that after reaching age 100 years, cognitive performance remains relatively stable during ensuing years. Therefore, these centenarians might be resilient or resistant against different risk factors of cognitive decline,” the authors wrote. They also speculate that resilience may be attributable to greater cognitive reserve.
“Our preliminary data indicate that approximately 60% of the chance to reach 100 years old is heritable. Therefore, to get a better understanding of which genetic factors associate with the prolonged maintenance of cognitive health, we are looking into which genetic variants occur more commonly in centenarians compared to younger individuals,” said Dr. Holstege.
“Of course, more research needs to be performed to get a better understanding of how such genetic elements might sustain brain health,” she added.
A ‘landmark study’
Commenting on the study in an interview, Thomas Perls, MD, MPH, professor of medicine, Boston University, called it a “landmark” study in research on exceptional longevity in humans.
Dr. Perls, the author of an accompanying editorial, noted that “one cannot absolutely assume a certain level or disability or risk for disease just because a person has achieved extreme age – in fact, if anything, their ability to achieve much older ages likely indicates that they have resistance or resilience to aging-related problems.”
Understanding the mechanism of the resilience could lead to treatment or prevention of AD, said Dr. Perls, who was not involved in the research.
“People have to be careful about ageist myths and attitudes and not have the ageist idea that the older you get, the sicker you get, because many individuals disprove that,” he cautioned.
The study was supported by Stichting Alzheimer Nederland and Stichting Vumc Fonds. Research from the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Dr. Holstege and Dr. Perls reported having no relevant financial relationships. The other authors’ disclosures are listed on the original article.
A version of this article first appeared on Medscape.com.
Investigators found that despite the presence of neuropathologies associated with Alzheimer’s disease (AD), many centenarians maintained high levels of cognitive performance.
“Cognitive decline is not inevitable,” senior author Henne Holstege, PhD, assistant professor, Amsterdam Alzheimer Center and Clinical Genetics, Amsterdam University Medical Center, said in an interview.
“At 100 years or older, high levels of cognitive performance can be maintained for several years, even when individuals are exposed to risk factors associated with cognitive decline,” she said.
The study was published online Jan. 15 in JAMA Network Open.
Escaping cognitive decline
Dr. Holstege said her interest in researching aging and cognitive health was inspired by the “fascinating” story of Hendrikje van Andel-Schipper, who died at age 115 in 2015 “completely cognitively healthy.” Her mother, who died at age 100, also was cognitively intact at the end of her life.
“I wanted to know how it is possible that some people can completely escape all aspects of cognitive decline while reaching extreme ages,” Dr. Holstege said.
To discover the secret to cognitive health in the oldest old, Dr. Holstege initiated the 100-Plus Study, which involved a cohort of healthy centenarians.
The investigators conducted extensive neuropsychological testing and collected blood and fecal samples to examine “the myriad factors that influence physical health, including genetics, neuropathology, blood markers, and the gut microbiome, to explore the molecular and neuropsychologic constellations associated with the escape from cognitive decline.”
The goal of the research was to investigate “to what extent centenarians were able to maintain their cognitive health after study inclusion, and to what extent this was associated with genetic, physical, or neuropathological features,” she said.
The study included 330 centenarians who completed one or more neuropsychological assessments. Neuropathologic studies were available for 44 participants.
To assess baseline cognitive performance, the researchers administered a wide array of neurocognitive tests, as well as the Mini–Mental State Examination, from which mean z scores for cognitive domains were calculated.
Additional factors in the analysis included sex, age, APOE status, cognitive reserve, physical health, and whether participants lived independently.
At autopsy, amyloid-beta (A-beta) level, the level of intracellular accumulation of phosphorylated tau protein in neurofibrillary tangles (NFTs), and the neuritic plaque (NP) load were assessed.
Resilience and cognitive reserve
At baseline, the median age of the centenarians (n = 330, 72.4% women) was 100.5 years (interquartile range, 100.2-101.7). A little over half (56.7%) lived independently, and the majority had good vision (65%) and hearing (56.4%). Most (78.8%) were able to walk independently, and 37.9% had achieved the highest International Standard Classification of Education level of postsecondary education.
The researchers found “varying degrees of neuropathology” in the brains of the 44 donors, including A-beta, NFT, and NPs.
The duration of follow-up in analyzing cognitive trajectories ranged from 0 to 4 years (median, 1.6 years).
Assessments of all cognitive domains showed no decline, with the exception of a “slight” decrement in memory function (beta −.10 SD per year; 95% confidence interval, –.14 to –.05 SD; P < .001).
Cognitive performance was associated with factors of physical health or cognitive reserve, for example, greater independence in performing activities of daily living, as assessed by the Barthel index (beta .37 SD per year; 95% CI, .24-.49; P < .001), or higher educational level (beta .41 SD per year; 95% CI, .29-.53; P < .001).
Despite findings of neuropathologic “hallmarks” of AD post mortem in the brains of the centenarians, these were not associated with cognitive performance or rate of decline.
APOE epsilon-4 or an APOE epsilon-3 alleles also were not significantly associated with cognitive performance or decline, suggesting that the “effects of APOE alleles are exerted before the age of 100 years,” the authors noted.
“Our findings suggest that after reaching age 100 years, cognitive performance remains relatively stable during ensuing years. Therefore, these centenarians might be resilient or resistant against different risk factors of cognitive decline,” the authors wrote. They also speculate that resilience may be attributable to greater cognitive reserve.
“Our preliminary data indicate that approximately 60% of the chance to reach 100 years old is heritable. Therefore, to get a better understanding of which genetic factors associate with the prolonged maintenance of cognitive health, we are looking into which genetic variants occur more commonly in centenarians compared to younger individuals,” said Dr. Holstege.
“Of course, more research needs to be performed to get a better understanding of how such genetic elements might sustain brain health,” she added.
A ‘landmark study’
Commenting on the study in an interview, Thomas Perls, MD, MPH, professor of medicine, Boston University, called it a “landmark” study in research on exceptional longevity in humans.
Dr. Perls, the author of an accompanying editorial, noted that “one cannot absolutely assume a certain level or disability or risk for disease just because a person has achieved extreme age – in fact, if anything, their ability to achieve much older ages likely indicates that they have resistance or resilience to aging-related problems.”
Understanding the mechanism of the resilience could lead to treatment or prevention of AD, said Dr. Perls, who was not involved in the research.
“People have to be careful about ageist myths and attitudes and not have the ageist idea that the older you get, the sicker you get, because many individuals disprove that,” he cautioned.
The study was supported by Stichting Alzheimer Nederland and Stichting Vumc Fonds. Research from the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Dr. Holstege and Dr. Perls reported having no relevant financial relationships. The other authors’ disclosures are listed on the original article.
A version of this article first appeared on Medscape.com.
Investigators found that despite the presence of neuropathologies associated with Alzheimer’s disease (AD), many centenarians maintained high levels of cognitive performance.
“Cognitive decline is not inevitable,” senior author Henne Holstege, PhD, assistant professor, Amsterdam Alzheimer Center and Clinical Genetics, Amsterdam University Medical Center, said in an interview.
“At 100 years or older, high levels of cognitive performance can be maintained for several years, even when individuals are exposed to risk factors associated with cognitive decline,” she said.
The study was published online Jan. 15 in JAMA Network Open.
Escaping cognitive decline
Dr. Holstege said her interest in researching aging and cognitive health was inspired by the “fascinating” story of Hendrikje van Andel-Schipper, who died at age 115 in 2015 “completely cognitively healthy.” Her mother, who died at age 100, also was cognitively intact at the end of her life.
“I wanted to know how it is possible that some people can completely escape all aspects of cognitive decline while reaching extreme ages,” Dr. Holstege said.
To discover the secret to cognitive health in the oldest old, Dr. Holstege initiated the 100-Plus Study, which involved a cohort of healthy centenarians.
The investigators conducted extensive neuropsychological testing and collected blood and fecal samples to examine “the myriad factors that influence physical health, including genetics, neuropathology, blood markers, and the gut microbiome, to explore the molecular and neuropsychologic constellations associated with the escape from cognitive decline.”
The goal of the research was to investigate “to what extent centenarians were able to maintain their cognitive health after study inclusion, and to what extent this was associated with genetic, physical, or neuropathological features,” she said.
The study included 330 centenarians who completed one or more neuropsychological assessments. Neuropathologic studies were available for 44 participants.
To assess baseline cognitive performance, the researchers administered a wide array of neurocognitive tests, as well as the Mini–Mental State Examination, from which mean z scores for cognitive domains were calculated.
Additional factors in the analysis included sex, age, APOE status, cognitive reserve, physical health, and whether participants lived independently.
At autopsy, amyloid-beta (A-beta) level, the level of intracellular accumulation of phosphorylated tau protein in neurofibrillary tangles (NFTs), and the neuritic plaque (NP) load were assessed.
Resilience and cognitive reserve
At baseline, the median age of the centenarians (n = 330, 72.4% women) was 100.5 years (interquartile range, 100.2-101.7). A little over half (56.7%) lived independently, and the majority had good vision (65%) and hearing (56.4%). Most (78.8%) were able to walk independently, and 37.9% had achieved the highest International Standard Classification of Education level of postsecondary education.
The researchers found “varying degrees of neuropathology” in the brains of the 44 donors, including A-beta, NFT, and NPs.
The duration of follow-up in analyzing cognitive trajectories ranged from 0 to 4 years (median, 1.6 years).
Assessments of all cognitive domains showed no decline, with the exception of a “slight” decrement in memory function (beta −.10 SD per year; 95% confidence interval, –.14 to –.05 SD; P < .001).
Cognitive performance was associated with factors of physical health or cognitive reserve, for example, greater independence in performing activities of daily living, as assessed by the Barthel index (beta .37 SD per year; 95% CI, .24-.49; P < .001), or higher educational level (beta .41 SD per year; 95% CI, .29-.53; P < .001).
Despite findings of neuropathologic “hallmarks” of AD post mortem in the brains of the centenarians, these were not associated with cognitive performance or rate of decline.
APOE epsilon-4 or an APOE epsilon-3 alleles also were not significantly associated with cognitive performance or decline, suggesting that the “effects of APOE alleles are exerted before the age of 100 years,” the authors noted.
“Our findings suggest that after reaching age 100 years, cognitive performance remains relatively stable during ensuing years. Therefore, these centenarians might be resilient or resistant against different risk factors of cognitive decline,” the authors wrote. They also speculate that resilience may be attributable to greater cognitive reserve.
“Our preliminary data indicate that approximately 60% of the chance to reach 100 years old is heritable. Therefore, to get a better understanding of which genetic factors associate with the prolonged maintenance of cognitive health, we are looking into which genetic variants occur more commonly in centenarians compared to younger individuals,” said Dr. Holstege.
“Of course, more research needs to be performed to get a better understanding of how such genetic elements might sustain brain health,” she added.
A ‘landmark study’
Commenting on the study in an interview, Thomas Perls, MD, MPH, professor of medicine, Boston University, called it a “landmark” study in research on exceptional longevity in humans.
Dr. Perls, the author of an accompanying editorial, noted that “one cannot absolutely assume a certain level or disability or risk for disease just because a person has achieved extreme age – in fact, if anything, their ability to achieve much older ages likely indicates that they have resistance or resilience to aging-related problems.”
Understanding the mechanism of the resilience could lead to treatment or prevention of AD, said Dr. Perls, who was not involved in the research.
“People have to be careful about ageist myths and attitudes and not have the ageist idea that the older you get, the sicker you get, because many individuals disprove that,” he cautioned.
The study was supported by Stichting Alzheimer Nederland and Stichting Vumc Fonds. Research from the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Dr. Holstege and Dr. Perls reported having no relevant financial relationships. The other authors’ disclosures are listed on the original article.
A version of this article first appeared on Medscape.com.
List of COVID-19 high-risk comorbidities expanded
The list of medical
according to the Centers for Disease Control and Prevention.The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.
On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”
Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.
The list of medical
according to the Centers for Disease Control and Prevention.The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.
On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”
Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.
The list of medical
according to the Centers for Disease Control and Prevention.The CDC’s latest list consists of 17 conditions or groups of related conditions that may increase patients’ risk of developing severe outcomes of COVID-19, the CDC said on a web page intended for the general public.
On a separate page, the CDC defines severe outcomes “as hospitalization, admission to the intensive care unit, intubation or mechanical ventilation, or death.”
Asthma is included in the newly expanded list with other chronic lung diseases such as chronic obstructive pulmonary disease and cystic fibrosis; the list’s heart disease entry covers coronary artery disease, heart failure, cardiomyopathies, and hypertension, the CDC said.
Green light puts the stop on migraine
small study from the University of Arizona, Tucson.
, according to results of a“This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, “ senior author Mohab M. Ibrahim, MD, PhD, said in a press release. “Now I have another tool in my toolbox to treat one of the most difficult neurologic conditions – migraine.”
“Given the safety, affordability, and efficacy of green light exposure, there is merit to conduct a larger study,” he and coauthors from the university wrote in their paper.
The study included 29 adult patients (average age 52.2 years), 22 with chronic migraine and the rest with episodic migraine who were recruited from the University of Arizona/Banner Medical Center chronic pain clinic. To be included, patients had to meet the International Headache Society diagnostic criteria for chronic or episodic migraine, have an average headache pain intensity of 5 out of 10 or greater on the numeric pain scale (NPS) over the 10 weeks prior to enrolling in the study, and be dissatisfied with their current migraine therapy.
The patients were free to start, continue, or discontinue any other migraine treatments as recommended by their physicians as long as this was reported to the study team.
White versus green
The one-way crossover design involved exposure to 10 weeks of white light emitting diodes, for 1-2 hours per day, followed by a 2-week washout period and then 10 weeks’ exposure to green light emitting diodes (GLED) for the same daily duration. The protocol involved use of a light strip emitting an intensity of between 4 and 100 lux measured at approximately 2 m and 1 m from a lux meter.
Patients were instructed to use the light in a dark room, without falling asleep, and to participate in activities that did not require external light sources, such as listening to music, reading books, doing exercises, or engaging in similar activities. The daily minimum exposure of 1 hour, up to a maximum of 2 hours, was to be completed in one sitting.
The primary outcome measure was the number of headache days per month, defined as days with moderate to severe headache pain for at least 4 hours. Secondary outcomes included perceived reduction in duration and intensity of the headache phase of the migraine episodes assessed every 2 weeks with the NPS, improved ability to fall and stay asleep, improved ability to perform work and daily activity, improved quality of life, and reduction of pain medications.
The researchers found that when the patients with chronic migraine and episodic migraine were examined as separate groups, white light exposure did not significantly reduce the number of headache days per month, but when the chronic migraine and episodic migraine groups were combined there was a significant reduction from 18.2 to 16.5 headache days per month.
On the other hand, green light did result in significantly reduced headache days both in the separate (from 7.9 to 2.4 days in the episodic migraine group and 22.3 to 9.4 days in the chronic migraine group) and combined groups (from 18.4 to 7.4 days).
“While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes,” the authors reported.
“The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them,” coauthor Amol M. Patwardhan, MD, PhD, said in the press release. “The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures,” said Dr. Patwardhan, associate professor and vice chair of research in the University of Arizona’s department of anesthesiology.
Better than white light
Asked to comment on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said research has shown for some time that exposure to green light has beneficial effects in migraine patients. This study, although small, does indicate that green light is more beneficial than is white light and reduces headache days and intensity. “I believe patients would be willing to spend 1-2 hours a day in green light to reduce and improve their migraine with few side effects. A larger randomized trial should be done,” he said.
The study was funded by support from the National Center for Complementary and Integrative Health (to Dr. Ibrahim), the Comprehensive Chronic Pain and Addiction Center–University of Arizona, and the University of Arizona CHiLLI initiative. Dr. Ibrahim and one coauthor have a patent pending through the University of Arizona for use of green light therapy for the management of chronic pain. Dr. Rapoport is a former president of the International Headache Society. He is an editor of Headache and CNS Drugs, and Editor-in-Chief of Neurology Reviews. He reviews for many peer-reviewed journals such as Cephalalgia, Neurology, New England Journal of Medicine, and Headache.
small study from the University of Arizona, Tucson.
, according to results of a“This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, “ senior author Mohab M. Ibrahim, MD, PhD, said in a press release. “Now I have another tool in my toolbox to treat one of the most difficult neurologic conditions – migraine.”
“Given the safety, affordability, and efficacy of green light exposure, there is merit to conduct a larger study,” he and coauthors from the university wrote in their paper.
The study included 29 adult patients (average age 52.2 years), 22 with chronic migraine and the rest with episodic migraine who were recruited from the University of Arizona/Banner Medical Center chronic pain clinic. To be included, patients had to meet the International Headache Society diagnostic criteria for chronic or episodic migraine, have an average headache pain intensity of 5 out of 10 or greater on the numeric pain scale (NPS) over the 10 weeks prior to enrolling in the study, and be dissatisfied with their current migraine therapy.
The patients were free to start, continue, or discontinue any other migraine treatments as recommended by their physicians as long as this was reported to the study team.
White versus green
The one-way crossover design involved exposure to 10 weeks of white light emitting diodes, for 1-2 hours per day, followed by a 2-week washout period and then 10 weeks’ exposure to green light emitting diodes (GLED) for the same daily duration. The protocol involved use of a light strip emitting an intensity of between 4 and 100 lux measured at approximately 2 m and 1 m from a lux meter.
Patients were instructed to use the light in a dark room, without falling asleep, and to participate in activities that did not require external light sources, such as listening to music, reading books, doing exercises, or engaging in similar activities. The daily minimum exposure of 1 hour, up to a maximum of 2 hours, was to be completed in one sitting.
The primary outcome measure was the number of headache days per month, defined as days with moderate to severe headache pain for at least 4 hours. Secondary outcomes included perceived reduction in duration and intensity of the headache phase of the migraine episodes assessed every 2 weeks with the NPS, improved ability to fall and stay asleep, improved ability to perform work and daily activity, improved quality of life, and reduction of pain medications.
The researchers found that when the patients with chronic migraine and episodic migraine were examined as separate groups, white light exposure did not significantly reduce the number of headache days per month, but when the chronic migraine and episodic migraine groups were combined there was a significant reduction from 18.2 to 16.5 headache days per month.
On the other hand, green light did result in significantly reduced headache days both in the separate (from 7.9 to 2.4 days in the episodic migraine group and 22.3 to 9.4 days in the chronic migraine group) and combined groups (from 18.4 to 7.4 days).
“While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes,” the authors reported.
“The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them,” coauthor Amol M. Patwardhan, MD, PhD, said in the press release. “The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures,” said Dr. Patwardhan, associate professor and vice chair of research in the University of Arizona’s department of anesthesiology.
Better than white light
Asked to comment on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said research has shown for some time that exposure to green light has beneficial effects in migraine patients. This study, although small, does indicate that green light is more beneficial than is white light and reduces headache days and intensity. “I believe patients would be willing to spend 1-2 hours a day in green light to reduce and improve their migraine with few side effects. A larger randomized trial should be done,” he said.
The study was funded by support from the National Center for Complementary and Integrative Health (to Dr. Ibrahim), the Comprehensive Chronic Pain and Addiction Center–University of Arizona, and the University of Arizona CHiLLI initiative. Dr. Ibrahim and one coauthor have a patent pending through the University of Arizona for use of green light therapy for the management of chronic pain. Dr. Rapoport is a former president of the International Headache Society. He is an editor of Headache and CNS Drugs, and Editor-in-Chief of Neurology Reviews. He reviews for many peer-reviewed journals such as Cephalalgia, Neurology, New England Journal of Medicine, and Headache.
small study from the University of Arizona, Tucson.
, according to results of a“This is the first clinical study to evaluate green light exposure as a potential preventive therapy for patients with migraine, “ senior author Mohab M. Ibrahim, MD, PhD, said in a press release. “Now I have another tool in my toolbox to treat one of the most difficult neurologic conditions – migraine.”
“Given the safety, affordability, and efficacy of green light exposure, there is merit to conduct a larger study,” he and coauthors from the university wrote in their paper.
The study included 29 adult patients (average age 52.2 years), 22 with chronic migraine and the rest with episodic migraine who were recruited from the University of Arizona/Banner Medical Center chronic pain clinic. To be included, patients had to meet the International Headache Society diagnostic criteria for chronic or episodic migraine, have an average headache pain intensity of 5 out of 10 or greater on the numeric pain scale (NPS) over the 10 weeks prior to enrolling in the study, and be dissatisfied with their current migraine therapy.
The patients were free to start, continue, or discontinue any other migraine treatments as recommended by their physicians as long as this was reported to the study team.
White versus green
The one-way crossover design involved exposure to 10 weeks of white light emitting diodes, for 1-2 hours per day, followed by a 2-week washout period and then 10 weeks’ exposure to green light emitting diodes (GLED) for the same daily duration. The protocol involved use of a light strip emitting an intensity of between 4 and 100 lux measured at approximately 2 m and 1 m from a lux meter.
Patients were instructed to use the light in a dark room, without falling asleep, and to participate in activities that did not require external light sources, such as listening to music, reading books, doing exercises, or engaging in similar activities. The daily minimum exposure of 1 hour, up to a maximum of 2 hours, was to be completed in one sitting.
The primary outcome measure was the number of headache days per month, defined as days with moderate to severe headache pain for at least 4 hours. Secondary outcomes included perceived reduction in duration and intensity of the headache phase of the migraine episodes assessed every 2 weeks with the NPS, improved ability to fall and stay asleep, improved ability to perform work and daily activity, improved quality of life, and reduction of pain medications.
The researchers found that when the patients with chronic migraine and episodic migraine were examined as separate groups, white light exposure did not significantly reduce the number of headache days per month, but when the chronic migraine and episodic migraine groups were combined there was a significant reduction from 18.2 to 16.5 headache days per month.
On the other hand, green light did result in significantly reduced headache days both in the separate (from 7.9 to 2.4 days in the episodic migraine group and 22.3 to 9.4 days in the chronic migraine group) and combined groups (from 18.4 to 7.4 days).
“While some improvement in secondary outcomes was observed with white light emitting diodes, more secondary outcomes with significantly greater magnitude including assessments of quality of life, Short-Form McGill Pain Questionnaire, Headache Impact Test-6, and Five-level version of the EuroQol five-dimensional survey without reported side effects were observed with green light emitting diodes,” the authors reported.
“The use of a nonpharmacological therapy such as green light can be of tremendous help to a variety of patients that either do not want to be on medications or do not respond to them,” coauthor Amol M. Patwardhan, MD, PhD, said in the press release. “The beauty of this approach is the lack of associated side effects. If at all, it appears to improve sleep and other quality of life measures,” said Dr. Patwardhan, associate professor and vice chair of research in the University of Arizona’s department of anesthesiology.
Better than white light
Asked to comment on the findings, Alan M. Rapoport, MD, clinical professor of neurology at the University of California, Los Angeles, said research has shown for some time that exposure to green light has beneficial effects in migraine patients. This study, although small, does indicate that green light is more beneficial than is white light and reduces headache days and intensity. “I believe patients would be willing to spend 1-2 hours a day in green light to reduce and improve their migraine with few side effects. A larger randomized trial should be done,” he said.
The study was funded by support from the National Center for Complementary and Integrative Health (to Dr. Ibrahim), the Comprehensive Chronic Pain and Addiction Center–University of Arizona, and the University of Arizona CHiLLI initiative. Dr. Ibrahim and one coauthor have a patent pending through the University of Arizona for use of green light therapy for the management of chronic pain. Dr. Rapoport is a former president of the International Headache Society. He is an editor of Headache and CNS Drugs, and Editor-in-Chief of Neurology Reviews. He reviews for many peer-reviewed journals such as Cephalalgia, Neurology, New England Journal of Medicine, and Headache.
FROM CEPHALALGIA
Simple blood test plus AI may flag early-stage Alzheimer’s disease
, raising the prospect of early intervention when effective treatments become available.
In a study, investigators used six AI methodologies, including Deep Learning, to assess blood leukocyte epigenomic biomarkers. They found more than 150 genetic differences among study participants with Alzheimer’s disease in comparison with participants who did not have Alzheimer’s disease.
All of the AI platforms were effective in predicting Alzheimer’s disease. Deep Learning’s assessment of intragenic cytosine-phosphate-guanines (CpGs) had sensitivity and specificity rates of 97%.
“It’s almost as if the leukocytes have become a newspaper to tell us, ‘This is what is going on in the brain,’ “ lead author Ray Bahado-Singh, MD, chair of the department of obstetrics and gynecology, Oakland University, Auburn Hills, Mich., said in a news release.
The researchers noted that the findings, if replicated in future studies, may help in providing Alzheimer’s disease diagnoses “much earlier” in the disease process. “The holy grail is to identify patients in the preclinical stage so effective early interventions, including new medications, can be studied and ultimately used,” Dr. Bahado-Singh said.
“This certainly isn’t the final step in Alzheimer’s research, but I think this represents a significant change in direction,” he told attendees at a press briefing.
The findings were published online March 31 in PLOS ONE.
Silver tsunami
The investigators noted that Alzheimer’s disease is often diagnosed when the disease is in its later stages, after irreversible brain damage has occurred. “There is currently no cure for the disease, and the treatment is limited to drugs that attempt to treat symptoms and have little effect on the disease’s progression,” they noted.
Coinvestigator Khaled Imam, MD, director of geriatric medicine for Beaumont Health in Michigan, pointed out that although MRI and lumbar puncture can identify Alzheimer’s disease early on, the processes are expensive and/or invasive.
“Having biomarkers in the blood ... and being able to identify [Alzheimer’s disease] years before symptoms start, hopefully we’d be able to intervene early on in the process of the disease,” Dr. Imam said.
It is estimated that the number of Americans aged 85 and older will triple by 2050. This impending “silver tsunami,” which will come with a commensurate increase in Alzheimer’s disease cases, makes it even more important to be able to diagnose the disease early on, he noted.
The study included 24 individuals with late-onset Alzheimer’s disease (70.8% women; mean age, 83 years); 24 were deemed to be “cognitively healthy” (66.7% women; mean age, 80 years). About 500 ng of genomic DNA was extracted from whole-blood samples from each participant.
The researchers used the Infinium MethylationEPIC BeadChip array, and the samples were then examined for markers of methylation that would “indicate the disease process has started,” they noted.
In addition to Deep Learning, the five other AI platforms were the Support Vector Machine, Generalized Linear Model, Prediction Analysis for Microarrays, Random Forest, and Linear Discriminant Analysis.
These platforms were used to assess leukocyte genome changes. To predict Alzheimer’s disease, the researchers also used Ingenuity Pathway Analysis.
Significant “chemical changes”
Results showed that the Alzheimer’s disease group had 152 significantly differentially methylated CpGs in 171 genes in comparison with the non-Alzheimer’s disease group (false discovery rate P value < .05).
As a whole, using intragenic and intergenic/extragenic CpGs, the AI platforms were effective in predicting who had Alzheimer’s disease (area under the curve [AUC], ≥ 0.93). Using intragenic markers, the AUC for Deep Learning was 0.99.
“We looked at close to a million different sites, and we saw some chemical changes that we know are associated with alteration or change in gene function,” Dr. Bahado-Singh said.
Altered genes that were found in the Alzheimer’s disease group included CR1L, CTSV, S1PR1, and LTB4R – all of which “have been previously linked with Alzheimer’s disease and dementia,” the researchers noted. They also found the methylated genes CTSV and PRMT5, both of which have been previously associated with cardiovascular disease.
“A significant strength of our study is the novelty, i.e. the use of blood leukocytes to accurately detect Alzheimer’s disease and also for interrogating the pathogenesis of Alzheimer’s disease,” the investigators wrote.
Dr. Bahado-Singh said that the test let them identify changes in cells in the blood, “giving us a comprehensive account not only of the fact that the brain is being affected by Alzheimer’s disease but it’s telling us what kinds of processes are going on in the brain.
“Normally you don’t have access to the brain. This gives us a simple blood test to get an ongoing reading of the course of events in the brain – and potentially tell us very early on before the onset of symptoms,” he added.
Cautiously optimistic
During the question-and-answer session following his presentation at the briefing, Dr. Bahado-Singh reiterated that they are at a very early stage in the research and were not able to make clinical recommendations at this point. However, he added, “There was evidence that DNA methylation change could likely precede the onset of abnormalities in the cells that give rise to the disease.”
Coinvestigator Stewart Graham, PhD, director of Alzheimer’s research at Beaumont Health, added that although the initial study findings led to some excitement for the team, “we have to be very conservative with what we say.”
He noted that the findings need to be replicated in a more diverse population. Still, “we’re excited at the moment and looking forward to seeing what the future results hold,” Dr. Graham said.
Dr. Bahado-Singh said that if larger studies confirm the findings and the test is viable, it would make sense to use it as a screen for individuals older than 65. He noted that because of the aging of the population, “this subset of individuals will constitute a larger and larger fraction of the population globally.”
Still early days
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that the investigators used an “interesting” diagnostic process.
“It was a unique approach to looking at and trying to understand what might be some of the biological underpinnings and using these tools and technologies to determine if they’re able to differentiate individuals with Alzheimer’s disease” from those without Alzheimer’s disease, said Dr. Snyder, who was not involved with the research.
“Ultimately, we want to know who is at greater risk, who may have some of the changing biology at the earliest time point so that we can intervene to stop the progression of the disease,” she said.
She pointed out that a number of types of biomarker tests are currently under investigation, many of which are measuring different outcomes. “And that’s what we want to see going forward. We want to have as many tools in our toolbox that allow us to accurately diagnose at that earliest time point,” Dr. Snyder said.
“At this point, [the current study] is still pretty early, so it needs to be replicated and then expanded to larger groups to really understand what they may be seeing,” she added.
Dr. Bahado-Singh, Dr. Imam, Dr. Graham, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, raising the prospect of early intervention when effective treatments become available.
In a study, investigators used six AI methodologies, including Deep Learning, to assess blood leukocyte epigenomic biomarkers. They found more than 150 genetic differences among study participants with Alzheimer’s disease in comparison with participants who did not have Alzheimer’s disease.
All of the AI platforms were effective in predicting Alzheimer’s disease. Deep Learning’s assessment of intragenic cytosine-phosphate-guanines (CpGs) had sensitivity and specificity rates of 97%.
“It’s almost as if the leukocytes have become a newspaper to tell us, ‘This is what is going on in the brain,’ “ lead author Ray Bahado-Singh, MD, chair of the department of obstetrics and gynecology, Oakland University, Auburn Hills, Mich., said in a news release.
The researchers noted that the findings, if replicated in future studies, may help in providing Alzheimer’s disease diagnoses “much earlier” in the disease process. “The holy grail is to identify patients in the preclinical stage so effective early interventions, including new medications, can be studied and ultimately used,” Dr. Bahado-Singh said.
“This certainly isn’t the final step in Alzheimer’s research, but I think this represents a significant change in direction,” he told attendees at a press briefing.
The findings were published online March 31 in PLOS ONE.
Silver tsunami
The investigators noted that Alzheimer’s disease is often diagnosed when the disease is in its later stages, after irreversible brain damage has occurred. “There is currently no cure for the disease, and the treatment is limited to drugs that attempt to treat symptoms and have little effect on the disease’s progression,” they noted.
Coinvestigator Khaled Imam, MD, director of geriatric medicine for Beaumont Health in Michigan, pointed out that although MRI and lumbar puncture can identify Alzheimer’s disease early on, the processes are expensive and/or invasive.
“Having biomarkers in the blood ... and being able to identify [Alzheimer’s disease] years before symptoms start, hopefully we’d be able to intervene early on in the process of the disease,” Dr. Imam said.
It is estimated that the number of Americans aged 85 and older will triple by 2050. This impending “silver tsunami,” which will come with a commensurate increase in Alzheimer’s disease cases, makes it even more important to be able to diagnose the disease early on, he noted.
The study included 24 individuals with late-onset Alzheimer’s disease (70.8% women; mean age, 83 years); 24 were deemed to be “cognitively healthy” (66.7% women; mean age, 80 years). About 500 ng of genomic DNA was extracted from whole-blood samples from each participant.
The researchers used the Infinium MethylationEPIC BeadChip array, and the samples were then examined for markers of methylation that would “indicate the disease process has started,” they noted.
In addition to Deep Learning, the five other AI platforms were the Support Vector Machine, Generalized Linear Model, Prediction Analysis for Microarrays, Random Forest, and Linear Discriminant Analysis.
These platforms were used to assess leukocyte genome changes. To predict Alzheimer’s disease, the researchers also used Ingenuity Pathway Analysis.
Significant “chemical changes”
Results showed that the Alzheimer’s disease group had 152 significantly differentially methylated CpGs in 171 genes in comparison with the non-Alzheimer’s disease group (false discovery rate P value < .05).
As a whole, using intragenic and intergenic/extragenic CpGs, the AI platforms were effective in predicting who had Alzheimer’s disease (area under the curve [AUC], ≥ 0.93). Using intragenic markers, the AUC for Deep Learning was 0.99.
“We looked at close to a million different sites, and we saw some chemical changes that we know are associated with alteration or change in gene function,” Dr. Bahado-Singh said.
Altered genes that were found in the Alzheimer’s disease group included CR1L, CTSV, S1PR1, and LTB4R – all of which “have been previously linked with Alzheimer’s disease and dementia,” the researchers noted. They also found the methylated genes CTSV and PRMT5, both of which have been previously associated with cardiovascular disease.
“A significant strength of our study is the novelty, i.e. the use of blood leukocytes to accurately detect Alzheimer’s disease and also for interrogating the pathogenesis of Alzheimer’s disease,” the investigators wrote.
Dr. Bahado-Singh said that the test let them identify changes in cells in the blood, “giving us a comprehensive account not only of the fact that the brain is being affected by Alzheimer’s disease but it’s telling us what kinds of processes are going on in the brain.
“Normally you don’t have access to the brain. This gives us a simple blood test to get an ongoing reading of the course of events in the brain – and potentially tell us very early on before the onset of symptoms,” he added.
Cautiously optimistic
During the question-and-answer session following his presentation at the briefing, Dr. Bahado-Singh reiterated that they are at a very early stage in the research and were not able to make clinical recommendations at this point. However, he added, “There was evidence that DNA methylation change could likely precede the onset of abnormalities in the cells that give rise to the disease.”
Coinvestigator Stewart Graham, PhD, director of Alzheimer’s research at Beaumont Health, added that although the initial study findings led to some excitement for the team, “we have to be very conservative with what we say.”
He noted that the findings need to be replicated in a more diverse population. Still, “we’re excited at the moment and looking forward to seeing what the future results hold,” Dr. Graham said.
Dr. Bahado-Singh said that if larger studies confirm the findings and the test is viable, it would make sense to use it as a screen for individuals older than 65. He noted that because of the aging of the population, “this subset of individuals will constitute a larger and larger fraction of the population globally.”
Still early days
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that the investigators used an “interesting” diagnostic process.
“It was a unique approach to looking at and trying to understand what might be some of the biological underpinnings and using these tools and technologies to determine if they’re able to differentiate individuals with Alzheimer’s disease” from those without Alzheimer’s disease, said Dr. Snyder, who was not involved with the research.
“Ultimately, we want to know who is at greater risk, who may have some of the changing biology at the earliest time point so that we can intervene to stop the progression of the disease,” she said.
She pointed out that a number of types of biomarker tests are currently under investigation, many of which are measuring different outcomes. “And that’s what we want to see going forward. We want to have as many tools in our toolbox that allow us to accurately diagnose at that earliest time point,” Dr. Snyder said.
“At this point, [the current study] is still pretty early, so it needs to be replicated and then expanded to larger groups to really understand what they may be seeing,” she added.
Dr. Bahado-Singh, Dr. Imam, Dr. Graham, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, raising the prospect of early intervention when effective treatments become available.
In a study, investigators used six AI methodologies, including Deep Learning, to assess blood leukocyte epigenomic biomarkers. They found more than 150 genetic differences among study participants with Alzheimer’s disease in comparison with participants who did not have Alzheimer’s disease.
All of the AI platforms were effective in predicting Alzheimer’s disease. Deep Learning’s assessment of intragenic cytosine-phosphate-guanines (CpGs) had sensitivity and specificity rates of 97%.
“It’s almost as if the leukocytes have become a newspaper to tell us, ‘This is what is going on in the brain,’ “ lead author Ray Bahado-Singh, MD, chair of the department of obstetrics and gynecology, Oakland University, Auburn Hills, Mich., said in a news release.
The researchers noted that the findings, if replicated in future studies, may help in providing Alzheimer’s disease diagnoses “much earlier” in the disease process. “The holy grail is to identify patients in the preclinical stage so effective early interventions, including new medications, can be studied and ultimately used,” Dr. Bahado-Singh said.
“This certainly isn’t the final step in Alzheimer’s research, but I think this represents a significant change in direction,” he told attendees at a press briefing.
The findings were published online March 31 in PLOS ONE.
Silver tsunami
The investigators noted that Alzheimer’s disease is often diagnosed when the disease is in its later stages, after irreversible brain damage has occurred. “There is currently no cure for the disease, and the treatment is limited to drugs that attempt to treat symptoms and have little effect on the disease’s progression,” they noted.
Coinvestigator Khaled Imam, MD, director of geriatric medicine for Beaumont Health in Michigan, pointed out that although MRI and lumbar puncture can identify Alzheimer’s disease early on, the processes are expensive and/or invasive.
“Having biomarkers in the blood ... and being able to identify [Alzheimer’s disease] years before symptoms start, hopefully we’d be able to intervene early on in the process of the disease,” Dr. Imam said.
It is estimated that the number of Americans aged 85 and older will triple by 2050. This impending “silver tsunami,” which will come with a commensurate increase in Alzheimer’s disease cases, makes it even more important to be able to diagnose the disease early on, he noted.
The study included 24 individuals with late-onset Alzheimer’s disease (70.8% women; mean age, 83 years); 24 were deemed to be “cognitively healthy” (66.7% women; mean age, 80 years). About 500 ng of genomic DNA was extracted from whole-blood samples from each participant.
The researchers used the Infinium MethylationEPIC BeadChip array, and the samples were then examined for markers of methylation that would “indicate the disease process has started,” they noted.
In addition to Deep Learning, the five other AI platforms were the Support Vector Machine, Generalized Linear Model, Prediction Analysis for Microarrays, Random Forest, and Linear Discriminant Analysis.
These platforms were used to assess leukocyte genome changes. To predict Alzheimer’s disease, the researchers also used Ingenuity Pathway Analysis.
Significant “chemical changes”
Results showed that the Alzheimer’s disease group had 152 significantly differentially methylated CpGs in 171 genes in comparison with the non-Alzheimer’s disease group (false discovery rate P value < .05).
As a whole, using intragenic and intergenic/extragenic CpGs, the AI platforms were effective in predicting who had Alzheimer’s disease (area under the curve [AUC], ≥ 0.93). Using intragenic markers, the AUC for Deep Learning was 0.99.
“We looked at close to a million different sites, and we saw some chemical changes that we know are associated with alteration or change in gene function,” Dr. Bahado-Singh said.
Altered genes that were found in the Alzheimer’s disease group included CR1L, CTSV, S1PR1, and LTB4R – all of which “have been previously linked with Alzheimer’s disease and dementia,” the researchers noted. They also found the methylated genes CTSV and PRMT5, both of which have been previously associated with cardiovascular disease.
“A significant strength of our study is the novelty, i.e. the use of blood leukocytes to accurately detect Alzheimer’s disease and also for interrogating the pathogenesis of Alzheimer’s disease,” the investigators wrote.
Dr. Bahado-Singh said that the test let them identify changes in cells in the blood, “giving us a comprehensive account not only of the fact that the brain is being affected by Alzheimer’s disease but it’s telling us what kinds of processes are going on in the brain.
“Normally you don’t have access to the brain. This gives us a simple blood test to get an ongoing reading of the course of events in the brain – and potentially tell us very early on before the onset of symptoms,” he added.
Cautiously optimistic
During the question-and-answer session following his presentation at the briefing, Dr. Bahado-Singh reiterated that they are at a very early stage in the research and were not able to make clinical recommendations at this point. However, he added, “There was evidence that DNA methylation change could likely precede the onset of abnormalities in the cells that give rise to the disease.”
Coinvestigator Stewart Graham, PhD, director of Alzheimer’s research at Beaumont Health, added that although the initial study findings led to some excitement for the team, “we have to be very conservative with what we say.”
He noted that the findings need to be replicated in a more diverse population. Still, “we’re excited at the moment and looking forward to seeing what the future results hold,” Dr. Graham said.
Dr. Bahado-Singh said that if larger studies confirm the findings and the test is viable, it would make sense to use it as a screen for individuals older than 65. He noted that because of the aging of the population, “this subset of individuals will constitute a larger and larger fraction of the population globally.”
Still early days
Commenting on the findings, Heather Snyder, PhD, vice president of medical and scientific relations at the Alzheimer’s Association, noted that the investigators used an “interesting” diagnostic process.
“It was a unique approach to looking at and trying to understand what might be some of the biological underpinnings and using these tools and technologies to determine if they’re able to differentiate individuals with Alzheimer’s disease” from those without Alzheimer’s disease, said Dr. Snyder, who was not involved with the research.
“Ultimately, we want to know who is at greater risk, who may have some of the changing biology at the earliest time point so that we can intervene to stop the progression of the disease,” she said.
She pointed out that a number of types of biomarker tests are currently under investigation, many of which are measuring different outcomes. “And that’s what we want to see going forward. We want to have as many tools in our toolbox that allow us to accurately diagnose at that earliest time point,” Dr. Snyder said.
“At this point, [the current study] is still pretty early, so it needs to be replicated and then expanded to larger groups to really understand what they may be seeing,” she added.
Dr. Bahado-Singh, Dr. Imam, Dr. Graham, and Dr. Snyder have reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM PLOS ONE
Excess deaths jump 23% in U.S. in 2020, mostly because of COVID-19
The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.
For comparison, the death rate increased by 2.5% or less annually in recent years.
At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.
“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.
COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
More than half a million excess deaths
Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.
Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.
Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.
Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.
In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States.
Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
‘Massive’ excessive mortality
“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.
“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.
This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”
Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.
A version of this article first appeared on Medscape.com.
The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.
For comparison, the death rate increased by 2.5% or less annually in recent years.
At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.
“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.
COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
More than half a million excess deaths
Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.
Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.
Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.
Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.
In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States.
Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
‘Massive’ excessive mortality
“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.
“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.
This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”
Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.
A version of this article first appeared on Medscape.com.
The United States saw nearly 23% more deaths than expected during the first 9 months of the pandemic, and almost three-quarters of those deaths involved COVID-19.
For comparison, the death rate increased by 2.5% or less annually in recent years.
At the same time, rates of deaths from heart disease, Alzheimer’s disease or dementia, and diabetes also increased from March 1, 2020, to Jan. 2, 2021, especially during COVID-19 surges.
“Excess deaths surged in the east in April, followed by extended summer and early winter surges concentrated in Southern and Western states, respectively. Many of these states weakly embraced, or discouraged, pandemic control measures and lifted restrictions earlier than other states,” lead author Steven H. Woolf, MD, MPH, from the Virginia Commonwealth University, Richmond, and colleagues wrote in a research letter published online April 2, 2021, in JAMA.
COVID-19 mortality included all deaths for which it was cited as an underlying or contributing cause in records from the District of Columbia and 49 states. North Carolina was excluded for insufficient data.
More than half a million excess deaths
Between March 1, 2020, and Jan. 2, 2021, the United States experienced 2,801,439 deaths, or 522,368 excess deaths. A total 72.4% of these events were attributed to COVID-19.
Not all racial and ethnic groups were equally represented. For example, the rate of excess deaths was higher among non-Hispanic Black populations, at 208.4 deaths per 100,000. Non-Hispanic White populations experienced 157 deaths per 100,000, and Hispanic populations experienced 139.8 deaths per 100,000.
Further, non-Hispanic Black individuals accounted for 16.9% of the excess deaths but only 12.5% of the U.S. population, which reflects “racial disparities in COVID-19 mortality,” the authors noted.
Not adjusting for population aging is a potential limitation, as was reliance on provisional data and the likelihood that some death certificates were inaccurate.
In February, Anthony S. Fauci, MD, chief medical adviser to President Joe Biden, stated that political divisions likely played a role in the 500,000-plus COVID-19–related deaths in the United States.
Then a report came out on March 26 indicating that a different U.S. response to the pandemic could have avoided almost 400,000 COVID-19 deaths. In addition, an April 1 study in the CDC’s Morbidity and Mortality Weekly Report revealed that COVID-19 is now the third leading cause of death in the United States, after heart disease and cancer.
‘Massive’ excessive mortality
“There is no more visible or alarming manifestation of the toll of the COVID-19 pandemic than the deaths it has caused. In this issue of JAMA, Dr. Woolf and colleagues provide updated analyses that demonstrate that the excess mortality in the U.S. between March 1, 2020, and Jan. 2, 2021, has been massive,” Alan Garber, MD, PhD, wrote in an accompanying editorial.
“It seems likely that COVID-19 will have contributed to nearly as many deaths in the U.S. as the great influenza pandemic of 1918, and more than in any influenza outbreak in the U.S. since then,” added Dr. Garber, provost of Harvard University in Cambridge, Mass.
This study of excess mortality illustrates what is at stake, he added. “Despite the scientific, medical and public health progress of recent decades, the loss of life attributable to the COVID-19 pandemic exceeds the mortality of major wars. No nation should squander this opportunity to do what it takes to prepare for the next one.”
Dr. Woolf and Dr. Garber disclosed no relevant financial relationships. The National Institutes of Health supported the research through its National Center for Advancing Translational Sciences and the National Institute on Aging.
A version of this article first appeared on Medscape.com.
Is there a need for tPA before thrombectomy in patients with stroke?
In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.
“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.
“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.
“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.
Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
“If in doubt, leave it out”
Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.
The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.
But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.
The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.
The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.
The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).
A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).
Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).
“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”
On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.
“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”
He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
Individualized approach probable
Dr. Majoie suggested that different patients may be suitable for the different approaches.
“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”
Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.
Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.
Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.
“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.
Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.
He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.
“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.
“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”
MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.
A version of this article first appeared on Medscape.com.
In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.
“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.
“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.
“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.
Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
“If in doubt, leave it out”
Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.
The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.
But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.
The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.
The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.
The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).
A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).
Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).
“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”
On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.
“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”
He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
Individualized approach probable
Dr. Majoie suggested that different patients may be suitable for the different approaches.
“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”
Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.
Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.
Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.
“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.
Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.
He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.
“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.
“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”
MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.
A version of this article first appeared on Medscape.com.
In a new randomized trial that investigated the question of whether thrombolysis can be omitted for patients with stroke who are undergoing endovascular thrombectomy for a large-vessel occlusion, results were similar for both approaches.
“From the MR CLEAN NO IV results, we cannot change standard practice, as we failed to show superiority of the direct endovascular approach, and we also didn’t meet the noninferiority criteria. So, the standard practice of giving tPA to those eligible still holds,” said co–lead investigator Yvo Roos, MD.
“But I think we can say that these results suggest that there may also not be such a need for tPA in patients who can go straight for endovascular therapy,” said Dr. Roos, who is professor of neurology at Amsterdam Medical Center.
“If we are not sure whether a patient is suitable for tPA because they have a higher bleeding risk, I think we can be reassured about missing the tPA out and going straight to endovascular treatment. So, if in doubt, leave it out,” he added.
Results of the MR CLEAN NO IV trial were presented at the International Stroke Conference sponsored by the American Heart Association.
“If in doubt, leave it out”
Dr. Roos noted that three trials have investigated the question regarding dropping thrombolysis for patients who can receive thrombectomy quickly. These are the DIRECT MT, SKIP, and DEVT studies. All of these trials were conducted in Asian countries, and none found differences in functional outcomes between the two approaches.
The largest of these studies – the DIRECT-MT trial, from China, which was a sister study to MR CLEAN NO IV – did show noninferiority of the direct endovascular approach to tPA plus endovascular treatment.
But because of differences in health care logistics and trial populations, the benefits and risks of dropping thrombolysis in Western countries are not known, explained Charles Majoie, MD, who is co–lead investigator of the current trial and is chair of neuroradiology at Amsterdam Medical Center.
The MR CLEAN NO IV trial was designed to show superiority of the direct endovascular approach with noninferiority for hemorrhage. It enrolled 540 European patients who were eligible for both thrombolysis and thrombectomy and who presented to a thrombectomy-capable center. They were randomly assigned to receive thrombolysis plus endovascular therapy or direct endovascular therapy alone.
The mean time from stroke onset to groin puncture (the start of endovascular therapy) was very fast in both groups – 130 minutes in the direct group, and 135 minutes in the tPA group.
The primary outcome was a shift analysis of the Modified Rankin Scale (mRS). On that outcome, the trial failed to show significant superiority of the direct approach (odds ratio, 0.88; 95% confidence interval, 0.65-1.19).
A good functional outcome (mRS, 0-2) was achieved in 49% of the direct thrombectomy group and in 51% of the tPA group (OR, 0.95; 95% CI, 0.65-1.40).
Safety results showed no difference in any of the hemorrhage endpoints between the two groups. The rate of symptomatic intracranial hemorrhage was actually numerically higher in the direct thrombectomy group (5.9% vs. 5.3%).
“One of the most intriguing results of this study is that there was no increase in hemorrhage in the tPA group,” Dr. Roos commented. “This is very surprising, as we have always thought thrombolysis causes an increased bleeding risk. But after these results, we may have to rethink that idea – perhaps it is not the tPA itself that causes bleeding risk but rather the opening up of the vessel.”
On the failure to show noninferiority of the direct approach, Dr. Roos suggested that the trial may have been underpowered in this respect.
“Our sister trial, DIRECT-MT, was a noninferiority study. They had 650 patients, and they just reached noninferiority,” he said. “In MR CLEAN NO IV, we were aiming for superiority, and we had fewer patients – 540. We didn’t show superiority, and we didn’t have quite enough patients to show noninferiority.”
He added that, considering all the four studies together, the results look very similar and suggest no difference between the two approaches.
Individualized approach probable
Dr. Majoie suggested that different patients may be suitable for the different approaches.
“I think we are heading for individualized treatment. If we have a young patient and the angiography suite is ready, we could probably skip tPA, but it would be for the neurologist/neuroradiologist to make individualized decisions on this,” he said. “We need to look at subgroups for more information.”
Another large trial that investigated this issue, SWIFT-DIRECT, is expected to be presented later this year. An Australian trial, DIRECT-SAFE, is ongoing and is at an early stage of recruitment.
Dr. Roos said that the data from all the trials will be combined for a more comprehensive analysis of the benefits and risks of the two approaches in various subgroups.
Commenting on the study was cochair of the ISC session at which it was presented, Tudor Jovin, MD, chair of neurology at Cooper University Hospital, Cherry Hill, N.J.
“Putting these results together with the previous Asian studies, I think we can say that direct thrombectomy without tPA is clearly not superior to the combined approach of tPA plus thrombectomy,” he said.
Dr. Jovin explained that, in theory, direct thrombectomy could be faster than the combined approach and that the risk for symptomatic intracerebral hemorrhage could be lower. But neither of these two possible benefits were seen in this study.
He agreed with Dr. Roos that MR CLEAN NO IV could have failed to show noninferiority of the direct strategy because the sample was not large enough.
“The results of the two approaches are very similar in this study and in the Asian studies, so it doesn’t appear that tPA adds very much, and it is associated with a significant increase in costs,” he said.
“The answer will probably be that there is not a ‘one-size-fits-all’ strategy, and we may end up using different approaches for different patient groups,” Dr. Jovin added. “Information on this will come from subgroups analyses from these trials.”
MR CLEAN NO-IV trial was part of the CONTRAST consortium, which is supported by the Netherlands Cardiovascular Research Initiative (an initiative of the Dutch Heart Foundation), the Brain Foundation Netherlands, Medtronic, Health-Holland, and Top Sector Life Sciences. The study received additional unrestricted funding from Stryker European Operations. Dr. Roos and Dr. Majoie are shareholders of Nico Lab.
A version of this article first appeared on Medscape.com.
FROM ISC 2021