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Statins tied to lower risk for parkinsonism
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research suggests. An observational study showed older adults taking statins had a lower risk for parkinsonism than their counterparts not taking statins – an effect that may be partially mediated by less severe intracranial atherosclerosis in statin users.
“These findings further support the idea that cerebrovascular disease pathologies accumulating in older brains may be an unrecognized contributor to the common occurrence of parkinsonism in old age,” the investigators wrote. “More importantly, these findings suggest that statins may have a potential therapeutic role in decreasing the magnitude of parkinsonism in older adults,” they added.
The study was published online in Neurology.
No clinical recommendations ... yet
The findings are based on 2,841 older adults enrolled in one of three ongoing clinical pathological studies at Rush Alzheimer’s Disease Center, Chicago.
Participants’ average age at baseline was 76 years, and 75% were women. None had parkinsonism at the start of the study. One-third of participants (n = 936) were taking statins. During an average follow-up of 6 years, 1,432 (50%) participants developed parkinsonism.
After controlling for demographics, vascular risk factors, and diseases, use of a statin at baseline was associated with a 16% lower risk for parkinsonism (hazard ratio, 0.84; 95% confidence interval, 0.74-0.96; P = .008). Compared with low-intensity statin therapy, moderate- or high-intensity statin therapy was associated with a 7% lower risk for parkinsonism (HR, 0.93; 95% CI, 0.87-1.00; P = .043).
The researchers also examined the brains of 1,044 people who died during the study at a mean age of 89 years. They found statin use prior to death was associated with a 37% lower odds of cerebral atherosclerosis, compared with no statin use prior to death (odds ratio, 0.63; 95% CI, 0.50-0.79; P < .001).
In a mediation analysis, both a direct (OR, 0.73; 95% CI, 0.54-0.93; P = .008) and an indirect (OR, 0.92; 95% CI, 0.88-0.97; P = .002) pathway via less severe cerebrovascular disease linked statins to parkinsonism, indicating that cerebral atherosclerosis mediated 17% of the association between statins and parkinsonism.
In line with other studies, there was no association between statins and other neurodegenerative pathologies, including Parkinson’s disease pathology. However, even older adults with a clinical diagnosis of Parkinson’s disease often show mixed brain pathologies, including cerebrovascular disease pathologies.
“Therefore, we think that statins may be beneficial against parkinsonism in patients with Parkinson’s disease, dependent on how much cerebrovascular disease pathologies they have, including atherosclerosis,” said study investigator Shahram Oveisgharan, MD, with Rush Alzheimer’s Disease Center, Rush University Medical Center, Chicago.
However, since the results stem from an observational study, “we do not yet recommend using statins in large scale for older adults at risk for parkinsonism,” Dr. Oveisgharan said.
A mixed picture
Reached for comment, Shaheen Lakhan, MD, neurologist in Newton, Massachusetts, noted that since statins were first discovered in the fermented broth of a common soil fungus in the late 1970s, they have proven to reduce cholesterol, heart disease, and stroke.
“The jury is out, however, on [their] effects on diseases such as dementia, autoimmune/inflammatory conditions, bacterial/viral infections, cancer, and parkinsonism,” he said.
“Also, the question often remains whether any benefit gained from statins is from cholesterol-lowering or through another mechanism. When there is such a mixed picture, it generally means that the drug has an effect, but not for everyone,” Dr. Lakhan said. “Much work must now be done to stratify for which patients are statins effective, ineffective, or even harmful in these conditions,” he added.
The study was supported by the National Institutes of Health. Dr. Oveisgharan and Dr. Lakhan have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Brain implant allows fully paralyzed patient to communicate
Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.
The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.
“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.
Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
Mechanism a ‘mystery’
Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.
Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.
In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.
The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.
Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.
A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.
Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.
Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
Controversial history
In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.
Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).
The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.
Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.
“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
Results ‘not stunningly good’
The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.
Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.
Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.
“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”
Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.
“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.
Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”
“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”
The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.
A version of this article first appeared on Medscape.com.
Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.
The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.
“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.
Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
Mechanism a ‘mystery’
Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.
Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.
In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.
The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.
Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.
A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.
Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.
Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
Controversial history
In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.
Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).
The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.
Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.
“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
Results ‘not stunningly good’
The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.
Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.
Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.
“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”
Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.
“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.
Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”
“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”
The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.
A version of this article first appeared on Medscape.com.
Using a commercially available implant and newly designed software, the patient, who was in the advanced stages of Lou Gehrig’s disease and unable to move his eyes, was able to interact with researchers and caregivers, requesting goulash, beer, and music from the band Tool, thanking the researchers who developed the technology and inviting his 4-year-old son to watch a Disney film.
The investigators note the study shows for the first time that communication is possible in patients in a completely locked-in state (CLIS) and offers hope for a better quality of life in this population.
“It should encourage them to live after artificial respiration and to ask for brain-computer interfaces before they become CLIS,” study investigator Niels Birbaumer, PhD, a professor emeritus of the University of Tübingen, Germany, said in an interview. The study was published online March 22 in Nature Communications.
Although the findings appear promising, they build on previous research that was the subject of a 2019 investigation by the largest grant-funding agency in Germany. This controversy prompted the institute that led the current research to appoint an independent expert to audit and monitor the new study.
Mechanism a ‘mystery’
Use of brain-computer interface (BCI) technology to allow ALS patients to communicate has increased in recent years. BCIs capture brain signals, transmit them to a computer, and convert them into a command that the computer carries out.
Previous research shows patients with ALS who retain eye movement and control have been able to use BCIs to communicate. However, until now, the technology has not worked as well in CLIS patients, who have full-body paralysis.
In 2019, German and Swiss researchers implanted two 64-microde arrays in the brain of a 34-year-old patient who was diagnosed with ALS in 2015.
The electrodes measure neuronal activity while an amplifier located on the outside of the patient’s skull amplifies the signals to a computer. Software created by the research team decodes the signals and translates them into commands.
Using an auditory feedback system, the patient was able to use his mind to modulate the pitch of a tone to either high (meaning “yes”) or low (meaning “no.”) Just how the brain does this is a mystery, Dr. Birbaumer said.
A speller program reads letters aloud, first in groups and then individually. When a group contained letters the patient needed to spell a word, he used auditory feedback to select the high-pitch tone.
Initially, the patient was able to correctly spell his name. Ultimately, he was able to form complete sentences. The patient correctly spelled words on 44 of the 107 days in that phase of the experiment, spelling an average of just one character per minute.
Still, the researchers note he was able to interact with his caretakers, family, and researchers, even offering input on changes to make the device more effective.
Controversial history
In 2017, Dr. Birbaumer and Ujwal Chaudhary, PhD, who is the lead author on this current study, published a study in PLOS Biology. That research analyzed a brain-monitoring technique that the scientists claimed enabled patients with ALS who were completely locked in to answer yes or no questions correctly.
Allegations from a whistleblower at the University of Tübingen, where Dr. Birbaumer was a senior professor and Dr. Chaudhary was a postdoctoral researcher, prompted an investigation by the Deutsche Forschungsgemeinschaft, or German Research Foundation (DFG).
The whistleblower claimed that the 2017 paper and a second study published in 2019 contained incomplete data and misrepresented the findings. The DFG investigation found evidence of scientific misconduct and required that Dr. Birbaumer return the grant he had received for the research. The agency also banned Dr. Birbaumer from applying for grants or serving as a grant reviewer for 5 years. Dr. Chaudhary was banned for 3 years. PLOS Biology later retracted the papers.
Both researchers have refuted the allegations and have reportedly sued the German Research Foundation.
“We have no information about the status of our lawsuit against the DFG; it’s still pending,” Dr. Birbaumer told this news organization. “I hope they investigate our present study because the study of 2017 they did not investigate carefully enough.”
Results ‘not stunningly good’
The controversial history prompted the Wyss Center, Geneva, which led this new study, to seek out at an independent BCI expert to audit and monitor the study.
Nick Ramsey, PhD, a professor of cognitive neuroscience at the Brain Center of the University Medical Center Utrecht, the Netherlands, agreed to take on the assignment in March 2020.
Dr. Ramsey has also conducted research on BCI in patients with ALS, but his work has not included patients in CLIS.
“I judged the study to be compliant with universal standards of scientific integrity,” Dr. Ramsey told this news organization. “I am confident that the data and results presented in the paper are valid and will withstand academic and medical scrutiny.”
Commenting on the new findings, Dr. Ramsey noted that the results of the study are “not stunningly good, as the user could only communicate during a limited number of days, and even then with considerable slowness,” Dr. Ramsey said. However, he added that the study does provide proof of principle that communication is possible in CLIS patients.
“The question remains whether a BCI implant continues to work well in these patients, as there are some indications that people in such a state may lose their mental capabilities within months or a few years as a result of the disease and can thus no longer generate a wish to communicate,” Dr. Ramsey said.
Responding to a query from this news organization, a spokesperson for Nature Communications declined to comment on the new study but said that journal editors are “are alert to controversies within each field and take care when considering submissions during the peer-review process.”
“We have rigorous policies to safeguard the integrity of the research we publish,” the spokesperson continued, “including to ensure that research has been conducted to a high ethical standard and is reported transparently.”
The research was funded by Wyss Center for Bio and Neuroengineering, Geneva and Deutsche Forschungsgemeinschaft. The authors have disclosed no relevant financial relationships. Dr. Ramsey received payment from the Wyss Center for his advisory role in this project.
A version of this article first appeared on Medscape.com.
FROM NATURE COMMUNICATIONS
New guidance on cannabis use for treatment-resistant epilepsy
A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.
The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.
“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.
“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
Appropriate patient populations
Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.
Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.
“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”
Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.
No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.
The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.
The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
Considerations for unapproved cannabinoids
The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.
The guidance document notes several reasons to use a regulated medication instead of an unregulated product:
- Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
- Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
- More scientific evidence is available for regulated products.
- Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
- Nonregulated products are rarely covered by insurance or other reimbursement.
Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.
The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.
Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”
“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
Dosing and adverse effects
Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.
“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.
The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.
Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.
“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”
Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.
“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”
Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.
A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.
The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.
“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.
“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
Appropriate patient populations
Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.
Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.
“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”
Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.
No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.
The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.
The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
Considerations for unapproved cannabinoids
The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.
The guidance document notes several reasons to use a regulated medication instead of an unregulated product:
- Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
- Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
- More scientific evidence is available for regulated products.
- Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
- Nonregulated products are rarely covered by insurance or other reimbursement.
Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.
The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.
Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”
“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
Dosing and adverse effects
Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.
“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.
The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.
Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.
“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”
Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.
“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”
Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.
A recent review article draws from existing clinical trials and clinical experience in New South Wales, Australia, to fill this gap with interim guidance for both pediatric and adult patients. The article was published in the British Journal of Clinical Pharmacology.
The only current U.S. guidelines are from the American Academy of Neurology’s position statement on the use of medical cannabis for neurologic disorders and the American Epilepsy Society’s position statement on cannabis as a treatment for epileptic seizures. The AAN statement “highlights the current evidence, which currently only supports [Food and Drug Administration]–approved CBD [cannabidiol] (Epidiolex) for specific epilepsy syndromes,” said Daniel Freedman, DO, an assistant professor of neurology at the University of Texas at Austin and coauthor of the AAN’s position statement.
“Rescheduling marijuana will enable researchers to study CBD, THC [tetrahydrocannabinol], and other cannabinoids in high-quality studies so that we can better understand what works and for which conditions,” said Dr. Freedman, who was not involved in the Australian guidance document. He noted that little consensus exists because little evidence exists outside the handful of trials for Epidiolex.
“There are some patients with epilepsy that can benefit from high-quality, pharmaceutical-grade CBD products,” Dr. Freedman said. “These patients need to be carefully identified by a neurologist or epileptologist and prescribed a legal, safe, quality-controlled, and FDA-regulated product.”
Appropriate patient populations
Drug-resistant epilepsy, defined as failure of two appropriate antiseizure medications, affects an estimated one third of people with epilepsy, the new guideline notes. Though many over-the-counter products are available at dispensaries in the 33 U.S. states that allow use of cannabis for medical purposes, Epidiolex (cannabidiol) is the only FDA-approved drug for epilepsy that contains a substance derived from cannabis and the only one for which evidence from randomized, controlled trials exists.
Dr. Freedman notes that hemp-derived CBD oils are classified differently in the United States than marijuana-derived CBD oil, including Epidiolex, and are loosely regulated supplements or food additives commonly seen, for example at gas station.
“The point I drive home to patients is that you wouldn’t get your antibiotics from a gas station, so please don’t get your seizure medication from there,” Dr. Freedman said. “Studies have been done on ‘over-the-counter’ CBD oils and shown that they have variable quality, sometimes no detectable CBD, and sometimes other chemicals added like THC.”
Studies of Epidiolex showed that cannabidiol more effectively reduced seizure frequency than placebo for pediatric patients with Dravet syndrome (42% reduction) and for pediatric and adult patients with Lennox-Gastaut syndrome (39% reduction) or tuberous sclerosis complex (49% reduction). Efficacy was similar across dosing from 10-50 mg/kg per day, but higher doses involved higher rates of serious adverse events.
No reliable evidence in humans exists for THC or other cannabinoids in treating epilepsy.
The Australian guidance recommends limiting cannabis treatment to patients with severe drug-resistant epilepsy; a diagnosis of Dravet syndrome, Lennox-Gastaut syndrome, or tuberous sclerosis complex; and previous treatment with four approved antiseizure medications and/or the ketogenic diet, epilepsy surgery, or neurostimulator. The authors provide specific criteria for each of these conditions and then address exceptional cases that may be considered outside that criteria, such as patients under 2 years old, severe epilepsy with extended or repeated hospitalization or ICU admission, or a dangerous seizure type. The review also includes a detailed list of exclusion criteria for CBD medicine use.
The authors advised a thorough consent process before prescribing any cannabinoids, including therapeutic goals and stopping criteria; the lack of evidence available on dosing, efficacy, and side effects; and the potential for dependence or withdrawal. Consent discussions should also note whether the products are unregistered and not covered by external payers (anything other than Epidiolex currently), any activity restrictions, and any implications for occupational drug screening.
Considerations for unapproved cannabinoids
The authors note several factors to consider if prescribing or recommending a nonapproved, nonregulated cannabis medicine, including the ”differences between registered plant-derived cannabis medicines, synthetic cannabis medicines, and unregistered hemp-derived products.” Epidiolex is plant derived while other cannabis-derived medications (Marinol, Syndos, and Cesamet) that have been approved for nonepilepsy conditions, such as nausea associated with chemotherapy, are synthetic.
The guidance document notes several reasons to use a regulated medication instead of an unregulated product:
- Manufacturing processes can differ for unregulated products, including inconsistency in batches and unknown shelf life.
- Quality control processes, including risk of impurities, are much better with regulated products, which also have a system in place for safety recalls.
- More scientific evidence is available for regulated products.
- Safety surveillance reporting is more robust and standardized for regulated products whereas adverse event reporting is less reliable for unregulated products.
- Nonregulated products are rarely covered by insurance or other reimbursement.
Legal considerations will also vary by jurisdiction. ”Right now in the U.S. we have a confused legality where state level programs are still technically illegal at the federal level and I imagine there are some quality differences amongst dispensaries and states,” Dr. Freedman said. “Whenever there is disagreement between state and federal laws, this creates tension for our patients.” He noted, for example, that a patient using a CBD product that contains THC may, even if legal in their state, be confiscated by the Transportation Security Administration at an airport since it is not FDA approved and is not legal, according to the Drug Enforcement Agency.
The authors noted that inadequate data on long-term CBD use and data on neurodevelopmental effects of THC in children, teens, and young adults means THC products should be contraindicated for these age groups. (Epidiolex has less than 2% THC.) Drug interactions should also be considered, particularly for clobazam, CYP3A4 inhibitors or inducers (including St. John’s wort), digoxin, or a mechanistic target of rapamycin inhibitor.
Dr. Freedman said that most neurologists are comfortable prescribing Epidiolex since it has FDA approval while prescribing unapproved products varies more in the field. “Now that many states have compassionate use programs for medical marijuana, some neurologists do this as well,” Dr. Freedman said. Patients often ask about unregulated CBD or CBD+THC products because they’re seen as “natural and therefore better than manufactured pharmaceuticals.”
“I think this is the naturalistic fallacy at work and try to educate my patients on that since our only high-level data to show marijuana products work for epilepsy comes from a pharmaceutical company,” Dr. Freedman said. “My reasons for hesitating on compassionate use are that there is often THC, with variable amounts of concentration, and we know that THC can harm the developing pediatric brain.”
Dosing and adverse effects
Pediatric and adult dosing differences need to be considered, and “patient response (efficacy and toxicity) to these medications varies widely,” the authors noted. They advised getting serum transaminases (ALT and AST) and total bilirubin levels before beginning treatment. All patients should begin Epidiolex at a low dose, such as 2-5 mg/kg per day of CBD in two divided doses, the authors advise, and titrate slowly while monitoring for side effects (no more than 5 mg/kg per day per week). The current dosing range for CBD is 5-20 mg/kg per day in two divided doses, with higher rates involving more risk of adverse events.
“Note that some cannabinoids auto-inhibit their own metabolism and some have active metabolites with longer half-lives,” the authors wrote. “Therefore, dose or frequency may need to be reduced over time, unless tolerance occurs.” These doses, specific to Epidiolex, “cannot necessarily be applied to other oral CBD formulations or other types of epilepsy.” This guidance also does not apply to inhaled or transdermal routes of administration.
The most common adverse events were sleepiness – which occurred in up to 60% of trial participants – as well as diarrhea, decreases in appetite and weight, and drug interactions. Risk of hepatotoxicity means there’s a need to monitor liver function and adjust dosing for patients with moderate or severe hepatic impairment. “Other short-term side effects reported only with THC-containing cannabinoid compounds include increased risk of cardiac and cerebrovascular events, anxiety and psychosis risk, dependency, and withdrawal,” the authors wrote.
Though no withdrawal syndrome has been linked to stopping CBD, the authors suggested decreasing the dose by 10% every 2 days if stopping is not urgent.
“The key points to this issue are that CBD and all marijuana products need to be safe and regulated,” Dr. Freedman said. “Any claims about them need to be backed by high-quality evidence looking at that specific product for that specific condition.”
Dr. Freedman noted the need for children to receive treatment from clinicians with expertise in their specific condition since many other evidence-based treatments exist even for patients with epilepsy syndromes that are difficult to treat, such as other medications, surgery, and specialized diets.
“We need to fix the inconsistent regulation between over-the-counter CBD products, state dispensaries, and federal laws,” Dr. Freedman added. “Any medicine being used to treat children should be held to the same FDA standard of safety and efficacy.”
Dr. Freedman and the authors had no conflicts of interest. No external funding was noted.
FROM THE BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
Restoring ‘sixth sense’ may reduce falls in Alzheimer’s
(AD), new research confirms.
Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.
However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.
The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.
“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”
The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
The ‘sixth hidden sense’
The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.
“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”
Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.
The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.
Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.
Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.
To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.
“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.
Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
Can therapy help?
Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.
“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.
Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.
While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.
“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.
“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”
Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.
Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.
The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AD), new research confirms.
Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.
However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.
The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.
“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”
The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
The ‘sixth hidden sense’
The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.
“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”
Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.
The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.
Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.
Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.
To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.
“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.
Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
Can therapy help?
Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.
“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.
Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.
While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.
“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.
“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”
Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.
Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.
The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
(AD), new research confirms.
Falls are twice as common in patients with AD versu older individuals without the disorder and significantly increase the likelihood of institutionalization.
However, researchers recorded fewer falls in patients with a better functioning vestibular system, which detects head movements and plays a critical role in spatial orientation, posture, gait, and balance.
The results suggest that improving vestibular function with currently available therapies may prevent falls, something the researchers will investigate in a new clinical trial launching next month.
“One of the most dangerous and impactful symptoms in terms of function in patients with Alzheimer’s disease is their increased predisposition to falls,” study investigator Yuri Agrawal, MD, department of otolaryngology–head and neck surgery, Johns Hopkins University School of Medicine, Baltimore, said in an interview. “Alzheimer’s is the sixth leading cause of death in the U.S., and some people actually say that that high mortality rate is because of their predisposition to falls and the injuries that occur.”
The study was published online Feb. 14 in the Journal of Alzheimer’s Disease.
The ‘sixth hidden sense’
The vestibular system consists of three semicircular canals, which detect rotational head movement, and two otolith organs called the utricle and the saccule, which sense linear head movements and the orientation of the head with respect to gravity.
“We call the vestibular system the sixth hidden sense because it’s not a conscious perception like taste or smell,” Dr. Agrawal said. “It’s constantly providing input to our brain about where we are in space.”
Dr. Agrawal and colleagues previously reported that vestibular loss is twice as common in Alzheimer’s patients as in cognitively unimpaired age-matched controls. Now, they wanted to know if this sensory loss was associated with an increased risk for falls in this population.
The study included 48 patients age greater than or equal to 60 years with mild-to-moderate AD between 2018 and 2020. They also included an age-matched control group of healthy controls with no cognitive impairment.
Researchers assessed vestibular function at baseline by measuring semicircular canal and saccular function. One test required participants to wear goggles and complete a series of tests with their eyes open and closed while researchers recorded their eye movement with video-oculography. They also measured participants’ balance using the Berg Balance Scale.
Relative to matched controls, AD patients exhibited increased lateral instability when their eyes were open (P = .033) and closed (P = .042). Studies suggest that lateral stability declines more quickly with age and that instability with eyes closed is the single biggest predictor of incident falls in community-dwelling adults.
To determine if poor vestibular function increased fall risk in patients with AD, researchers followed the cohort for up to 2 years.
“We found that patients with vestibular loss at baseline were 50% more likely to fall, adjusting for other factors that could contribute to that,” Dr. Agrawal said.
Specifically, better semicircular canal function was significantly associated with lower likelihood of falls, even after adjusting for confounders (adjusted hazard ratio, 0.65; P = .009).
Can therapy help?
Commenting on the findings, James Burke, MD, PhD, professor of neurology at Duke University Medical Center, Durham, N.C., said that the finding that impaired vestibular function is associated with increased falls “significantly advances our understanding of the topic” and suggests that treating vestibular dysfunction could reduce falls in Alzheimer’s patients.
“Screening patients with Alzheimer’s disease for impaired vestibular function could lead to identification of individuals at high risk of falls and target those who would benefit from vestibular therapy,” he said.
Vestibular rehabilitation therapy is often used to treat a number of disorders related to vestibular function loss. There are also studies underway to measure the efficacy of a vestibular implant that works much like a cochlear implant.
While evaluation of vestibular function is currently not routinely included in AD care, studies such as these suggest it may be time to consider adding it to the standard of care, Jennifer Coto, PhD, assistant professor of otolaryngology at the University of Miami Miller School of Medicine, said in an interview.
“Best practice guidelines for management of Alzheimer’s patients should be revised to include routine vestibular evaluation and support from a multidisciplinary team that may address other crucial areas of functioning, particularly psychological functioning, sleep, and independence,” she said.
“Future research also needs to evaluate the effectiveness of vestibular therapy in patients with Alzheimer’s and the benefits of early identification and intervention for preventing recurrent falls.”
Dr. Agrawal is leading a 5-year, $3.5 million National Institute on Aging study that seeks to do just that. Enrollment in the study begins next month. Patients will complete an initial in-person screening, but the remainder of the study will be conducted virtually.
Therapies will be noninvasive, nonpharmaceutical, and performed in participants’ homes. If the therapy is successful at reducing falls, Dr. Agrawal said the virtual design would significantly broaden its potential patient reach.
The study was funded by the National Institute on Aging. Study authors’ disclosures are reported in the original article. Dr. Coto and Dr. Burke report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF ALZHEIMER’S DISEASE
Just one extra drink a day may change the brain
It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.
Now, new evidence published in Nature Communications suggests
Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.
But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.
The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.
But could even this modest amount of alcohol make a difference to our brains?
Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.
In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.
But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.
Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.
Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.
The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.
And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.
Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.
A version of this article first appeared on WebMD.com.
It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.
Now, new evidence published in Nature Communications suggests
Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.
But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.
The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.
But could even this modest amount of alcohol make a difference to our brains?
Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.
In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.
But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.
Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.
Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.
The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.
And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.
Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.
A version of this article first appeared on WebMD.com.
It’s no secret that heavy drinking is linked to potential health problems, from liver damage to a higher risk of cancer. But most people probably wouldn’t think a nightcap every evening is much of a health threat.
Now, new evidence published in Nature Communications suggests
Previous research has found that people with alcohol use disorder have structural changes in their brains, compared with healthy people’s brains, such as reduced gray-matter and white-matter volume.
But those findings were in people with a history of heavy drinking, defined by the National Institute on Alcohol Abuse and Alcoholism as more than four drinks a day for men and more than three drinks a day for women.
The national dietary guidelines from the U.S. Department of Health & Human Services advise drinking no more than two standard drinks for men and one drink for women each day. A standard drink in the United States is 12 ounces of beer, 5 ounces of wine, or 1½ ounce of liquor.
But could even this modest amount of alcohol make a difference to our brains?
Researchers examined functional MRI brain scans from 36,678 healthy adults, aged 40-69 years, in the United Kingdom and compared those findings with their weekly alcohol consumption, adjusting for differences in age, sex, height, social and economic status, and country of residence, among other things.
In line with past studies, the researchers found that, as a person drank more alcohol, their gray-matter and white-matter volume decreased, getting worse the more drinks they had in a week.
But the researchers also noted that they could tell the difference between brain images of people who never drank alcohol and those who had just one or two drinks a day.
Going from 1 unit of alcohol to 2 – which in the United Kingdom means a full pint of beer or standard glass of wine – was linked to changes similar to 2 years of aging in the brain.
Other than comparing the changes with aging, it’s not yet clear what the findings mean until the scientists do more research, including looking at the genes of the people who took part in the study.
The study also has several drawbacks. The people who were studied are all middle-aged Europeans, so findings might be different in younger people or those with different ancestries. People also self-reported how much alcohol they drank for the past year, which they might not remember correctly or which might be different from previous years, including past years of heavy drinking.
And since the researchers compared drinking habits with brain imaging at one point in time, it’s not possible to say whether alcohol is actually causing the brain differences they saw.
Still, the findings raise the question of whether national guidelines should be revisited, and whether it’s better to cut that evening drink to a half-glass of wine instead.
A version of this article first appeared on WebMD.com.
FROM NATURE COMMUNICATIONS
Targeting the endocannabinoid system in migraine
, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.
Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
Not just cannabis
In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.
The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”
Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.
There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.
Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.
Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.
“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
Patients are taking cannabinoids; physicians should learn about them
Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.
“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”
The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.
, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.
Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
Not just cannabis
In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.
The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”
Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.
There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.
Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.
Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.
“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
Patients are taking cannabinoids; physicians should learn about them
Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.
“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”
The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.
, according to Italian researchers at the University of Pavia, and the C. Mondino National Institute of Neurology Foundation. “The complexity of the endocannabinoid system calls for accurate biochemical and pharmacological characterization of any new compounds undergoing testing and development,” noted Rosaria Greco, PhD. She and her colleagues authored a review on the topic that was published online Feb. 18, 2022, in Headache.
Although cannabis has been investigated for both the treatment and prevention of migraine, evidence for its benefit is weak because of lack of controlled studies, they explained. Archival data from a large database “showed greater improvements in men than in women and suggested that concentrated preparations were more effective than flower consumption.” In addition, a small single-center study linked nabilone, a synthetic cannabinoid, to reductions in pain duration, intensity, and daily intake of analgesics among patients with medication overuse headache. Finally, a pilot study reported a reduction in pain intensity among patients with chronic migraine treated with a combination of tested a combination of delta-9-tetrahydrocannabinol and cannabidiol. “Methodologically sound studies are now needed to investigate the possible effects of cannabis in migraine treatment and to define strains, formulations, and dosage,” they noted.
Not just cannabis
In addition to exogenous cannabis, there are now preclinical studies suggesting other compounds that interact with the endocannabinoid system “are also able to modulate the pathways involved in migraine-related pain,” the study authors wrote. “But the road ahead is still long. Multiple molecules linked to the endocannabinoid system have emerged as potential therapeutic targets.
The complexity of the system demands caution and precise biochemical and pharmacological characterization of the new compounds to be tested and developed.”
Among these compounds are endogenous ligands such as N-arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol that specifically target CB1 and CB2 receptors. Additionally, there are endocannabinoid-based drugs that also target the CB1/CB2 receptors, as well as other substances, such as lipids (palmitoylethanolamide [PEA]) and enzymes, that do not bind to the CB1/CB2 receptors but are responsible for endocannabinoid biosynthesis.
There is some evidence that the endocannabinoid system may be dysfunctional in patients with migraine, and the authors noted their work has shown that PEA plasma levels are increased during experimentally triggered migraine-like attacks. Thus, some preclinical and preliminary evidence suggests that administration of PEA or anandamide may have analgesic and anti-inflammatory effects in migraine.
Another approach is the inhibition of endocannabinoid catabolic enzymes, which could circumvent the adverse effects associated with direct activation of CB receptors. “Endocannabinoid tone enhancement has been proposed as an alternative modality of activation of CB receptors and is possibly devoid of the psychotropic effects reported with CB receptor agonists,” noted the authors, who have shown in animal and preclinical studies that inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase can modulate migraine pain.
Yet another way of indirectly impacting CB receptors is through their allosteric ligands, an approach that “deserves further investigation”, and “might provide interesting leads for clinical development, given that it may have a favorable side-effect profile with limited psychomimetic and depressant effects,” wrote the authors. And finally, inhibition of N-acylethanolamine acid amide hydrolase, the enzyme that preferentially hydrolyzes PEA, might be a promising approach.
“The multiplicity of options and the wealth of data already obtained in animal models underscore the importance of further advancing research in this area,” the authors concluded.
Patients are taking cannabinoids; physicians should learn about them
Commenting on the paper, Alan Rapaport, MD, clinical professor of neurology at the University of California, Los Angeles, said “this well-done paper points out the complexity of the endocannabinoid system and the multiple ways of getting it to work for certain patients. It details some of the studies that show beneficial results in migraine, medication overuse headache, chronic migraine, and pain. Patients with headache, other types of pain, anxiety, nausea, sleep issues, and other symptoms are already taking cannabinoids, usually derived from the marijuana plant, that are not well regulated. A few are prescribed drugs which target CB1 and CB2 receptors. Patients often get relief of some of their symptoms, sometimes getting high and many times not.
“The paper makes the point that previous studies are often small, not carefully controlled, or well documented. We do need to start doing larger, properly designed studies and getting them into the literature. Doctors need to learn more about these treatments. The next step will be to get [Food and Drug Administration]–approved treatments, so physicians and nurses will know exactly what we are giving, the beneficial effects to expect in a certain percentage of patients, and the adverse events to warn our patients about. Cannabinoids have been tried by a large percentage of patients with headache and pain. Now we need to standardize the various treatments that are sure to be suggested in the future.”
The study was funded by the Migraine Research Foundation, and the Italian Ministry of Health. The study authors declared no conflicts of interest.
FROM HEADACHE
Amazonian indigenous groups have world’s lowest rate of dementia
What to know
- Only about 1% of members of the Tsimane and Moseten peoples of the Bolivian Amazon suffer from dementia, compared with 11% of people aged 65 and older in the United States.
- Underscoring the profound relationship between lifestyle and cognitive health, something about the preindustrial subsistence lifestyle of the groups appears to protect older tribe members from dementia.
- The rate of generally accepted as typical in aging is comparable between the tribes and rates in developed countries such as the United States.
- The Tsimane and Moseten people remain very physically active throughout their lives by fishing, hunting, and farming and experience less brain atrophy than their American and European peers.
- Indigenous populations elsewhere in the world have been found to have high rates of dementia, which are attributed to more contact with their nonindigenous neighbors and adoption of their lifestyles.
--From staff reports
This is a summary of the article, “Study: Some of the world’s lowest rates of dementia found in Amazonian indigenous groups,” published by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, on March 9, 2022. The full article can be found on news.ucsb.edu.
A version of this article first appeared on Medscape.com.
What to know
- Only about 1% of members of the Tsimane and Moseten peoples of the Bolivian Amazon suffer from dementia, compared with 11% of people aged 65 and older in the United States.
- Underscoring the profound relationship between lifestyle and cognitive health, something about the preindustrial subsistence lifestyle of the groups appears to protect older tribe members from dementia.
- The rate of generally accepted as typical in aging is comparable between the tribes and rates in developed countries such as the United States.
- The Tsimane and Moseten people remain very physically active throughout their lives by fishing, hunting, and farming and experience less brain atrophy than their American and European peers.
- Indigenous populations elsewhere in the world have been found to have high rates of dementia, which are attributed to more contact with their nonindigenous neighbors and adoption of their lifestyles.
--From staff reports
This is a summary of the article, “Study: Some of the world’s lowest rates of dementia found in Amazonian indigenous groups,” published by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, on March 9, 2022. The full article can be found on news.ucsb.edu.
A version of this article first appeared on Medscape.com.
What to know
- Only about 1% of members of the Tsimane and Moseten peoples of the Bolivian Amazon suffer from dementia, compared with 11% of people aged 65 and older in the United States.
- Underscoring the profound relationship between lifestyle and cognitive health, something about the preindustrial subsistence lifestyle of the groups appears to protect older tribe members from dementia.
- The rate of generally accepted as typical in aging is comparable between the tribes and rates in developed countries such as the United States.
- The Tsimane and Moseten people remain very physically active throughout their lives by fishing, hunting, and farming and experience less brain atrophy than their American and European peers.
- Indigenous populations elsewhere in the world have been found to have high rates of dementia, which are attributed to more contact with their nonindigenous neighbors and adoption of their lifestyles.
--From staff reports
This is a summary of the article, “Study: Some of the world’s lowest rates of dementia found in Amazonian indigenous groups,” published by Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, on March 9, 2022. The full article can be found on news.ucsb.edu.
A version of this article first appeared on Medscape.com.
First ‘before-and-after’ COVID-19 brain imaging study shows structural changes
, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.
The findings were published online March 7 in the journal Nature.
Gray matter loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at the time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.
Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More research needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.
A version of this article first appeared on Medscape.com.
, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.
The findings were published online March 7 in the journal Nature.
Gray matter loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at the time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.
Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More research needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.
A version of this article first appeared on Medscape.com.
, a new imaging study shows.
In the first study to use magnetic resonance brain imaging, before and after COVID-19, investigators found “greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, greater changes in markers of tissue damage in regions functionally connected to the primary olfactory cortex and greater reduction in global brain size.” However, the researchers urge caution when interpreting the findings.
Gwenaëlle Douaud, PhD, Wellcome Center for Integrative Neuroimaging, Nuffield Department of Clinical Neurosciences, University of Oxford, England, and colleagues describe these brain changes as “modest.”
“Whether these abnormal changes are the hallmark of the spread of the pathogenic effects in the brain, or of the virus itself, and whether these may prefigure a future vulnerability of the limbic system in particular, including memory, for these participants, remains to be investigated,” the researchers wrote.
The findings were published online March 7 in the journal Nature.
Gray matter loss
The investigators analyzed data from the UK Biobank, a large-scale biomedical database with genetic and health information for about 500,000 individuals living in the UK. They identified 785 adults aged 51-81 years who had undergone two brain MRIs about 3 years apart. Of these, 401 tested positive for SARS-CoV-2 before the second scan.
Participants also completed cognitive tests at the time of both scans.
Biobank centers use identical MRI scans and scanning methods, including six types of MRI scans, to image distinct regions of the brain and brain function. Results showed that although some loss of gray matter over time is normal, individuals who were infected with SARS-CoV-2 showed a 0.2% to 2% brain tissue loss in the parahippocampal gyrus, the orbitofrontal cortex, and the insula – all of which are largely involved in the sense of smell.
Participants who had contracted COVID-19 also showed a greater reduction in overall brain volume and a decrease in cognitive function.
Most of those with COVID-19 had only mild or moderate symptoms. However, the findings held even after the researchers excluded patients who had been hospitalized.
More research needed
“These findings might help explain why some people experience brain symptoms long after the acute infection,” Max Taquet, PhD, National Institute for Health Research Oxford Health BRC senior research fellow, University of Oxford, said in a press release.
Dr. Taquet, who was not a part of the study, noted the causes of these brain changes remain to be determined. Questions remain as to “whether they can be prevented or even reverted, as well as whether similar changes are observed in hospitalized patients,” children, younger adults, and minority groups.
“It is possible that these brain changes are not caused by COVID-19 but represent the natural progression of a disease that itself increased the risk of COVID-19,” Dr. Taquet said.
Other experts expressed concern over the findings and emphasized the need for more research.
“I am very concerned by the alarming use of language in the report with terms such as ‘neurodegenerative,’ “ Alan Carson, MD, professor of neuropsychiatry at the Center for Clinical Brain Sciences at the University of Edinburgh, Scotland, said in a press release. “The size and magnitude of brain changes found is very modest and such changes can be caused by a simple change in mental experience,” Dr. Carson said.
“What this study almost certainly shows is the impact, in terms of neural changes, of being disconnected from one’s sense of smell,” he added.
The study was funded by the Wellcome Trust Collaborative. Full financial conflict information for the study authors is included in the original article. Dr. Taquet has collaborated previously with some of the investigators.
A version of this article first appeared on Medscape.com.
From Nature
Dietary fiber tied to lower dementia risk
, new research shows.
Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.
“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.
“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.
The study was published online Feb. 6 in Nutritional Neuroscience.
Brain-gut interaction
Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.
A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.
The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.
In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.
“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”
The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.
Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.
“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.
The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
Unclear mechanism
During follow-up, 670 participants developed disabling dementia.
Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).
The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).
“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.
“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.
“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”
The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.
In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
Balance is key
In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”
Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.
“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.
The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.
“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.
“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.
The study was published online Feb. 6 in Nutritional Neuroscience.
Brain-gut interaction
Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.
A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.
The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.
In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.
“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”
The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.
Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.
“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.
The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
Unclear mechanism
During follow-up, 670 participants developed disabling dementia.
Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).
The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).
“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.
“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.
“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”
The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.
In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
Balance is key
In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”
Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.
“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.
The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
, new research shows.
Investigators administered a dietary survey to 3,700 healthy adults at midlife and then followed them for up to 20 years. They found that participants who consumed the most fiber had approximately a 25% lower risk of developing dementia in later life.
“This study showed that people with a high intake of dietary fiber, especially soluble fiber, have a lower risk of dementia,” study investigator Kazumasa Yamagishi, MD, PhD, professor, department of public health medicine, faculty of medicine and health, Services Research and Development Center, University of Tsukuba, Japan, said in an interview.
“There are still many unknowns about the causes of dementia, and it is not appropriate to determine causality based on the results of a single cohort study. However, the results of this study can be said to be one of the findings that will lead to the prevention of dementia,” Dr. Yamagishi said.
The study was published online Feb. 6 in Nutritional Neuroscience.
Brain-gut interaction
Brain-gut interaction has recently received attention for its potential involvement in the development of dementia. “The concept of brain-gut interaction emerged from the idea that the central nervous system communicates bidirectionally with the gastrointestinal tract, suggesting that the gut microbiome may influence brain plasticity and cognitive function,” the authors wrote.
A diet high in soluble fiber attenuates neuroinflammation in mouse models. Other animal studies have suggested that insoluble fiber might also have a beneficial effect on the microbiome.
The researchers wanted to see whether dietary fiber intake – especially soluble fiber – is associated with a reduced risk of dementia. They also investigated whether there was any difference between dementia in patients with vs. without a history of stroke.
In a previous study, these same researchers reported an inverse association between eating beans, which are high in fiber, and risk of disabling dementia. In the current study, the researchers extended the analyses to dietary fiber intake of total, soluble, and insoluble fibers, as well as other fiber-containing foods, such potatoes, vegetables, and fruits. However, they distinguished potatoes from other vegetables because the composition of starch in potatoes differs.
“Dietary fiber is a nutrient found in grains, potatoes, vegetables, and fruits and is known to affect intestinal bacteria,” Dr. Yamagishi said. “Recently, some experimental studies have shown that intestinal bacteria may be involved in cognitive functions as well as diseases of the digestive tract. However, there have been no studies that have actually examined the relationship between dietary fiber intake and the subsequent risk of dementia in large numbers of general people.”
The researchers turned to participants in the Circulatory Risk in Communities Study (CIRCS), an ongoing dynamic community cohort study involving five communities in Japan. The current study focused on communities where disabling dementia surveillance is conducted.
Participants (n = 3,739) ranged in age from 40 to 64 years (mean age, 51 years) at the time they completed the 24-hour dietary recall survey, and they participated in annual health checkups from 1985 to 1999. Potential risk factors for disabling dementia were measured at the time the dietary surveys were conducted. Participants were then followed for a median of 19.7 years (1999-2020) to confirm incident, disabling dementia.
“Disabling dementia” was defined as dementia that required care under the National Long-Term Care Insurance System and was further categorized on the basis of having a history or not having a history of stroke.
The researchers divided participants into quartiles, based on the amount of total, soluble, and insoluble intake reported in their surveys. They found that men tended to consume less total fiber compared to women.
Unclear mechanism
During follow-up, 670 participants developed disabling dementia.
Total fiber intake was “inversely and linearly” associated with risk of incident dementia, the authors reported, with each successive quartile associated with a lower risk compared to the lowest quartile (P for trend = .03).
The association remained after adjustment for potential factors that might affect dementia onset, such as body mass index, systolic blood pressure, antihypertensive medication use, serum total cholesterol, cholesterol-lowering medication, and diabetes (P for trend = .05).
“The inverse association was more evident for soluble fiber intake and was confined to dementia without a history of stroke,” the authors reported. Moreover, potatoes, not vegetables or fruits, showed a similar association.
“The mechanisms are currently unknown but might involve the interactions that take place between the gut and the brain,” Dr. Yamagishi said in a release.
“One possibility is that soluble fiber regulates the composition of gut bacteria. This composition may affect neuroinflammation, which plays a role in the onset of dementia,” he suggested. “It’s also possible that dietary fiber may reduce other risk factors for dementia, such as body weight, blood pressure, lipids, and glucose levels.”
The authors noted several limitations. For example, they did not distinguish between Alzheimer’s and non-Alzheimer’s dementia. Moreover, they classified dietary habits on the basis of a single survey, and participants’ dietary patterns might have changed over the study period.
In addition, Dr. Yamagishi noted, it is “important to confirm the association in other populations.”
Balance is key
In an interview, Uma Naidoo, MD, director of nutritional and lifestyle psychiatry, Massachusetts General Hospital, and nutrition educator at Harvard Medical School, both in Boston, said the study “adds to the growing pool of evidence suggesting that a diet rich in colorful, plant-based foods can benefit our neurological and psychiatric health, especially as we age.”
Dr. Naidoo, a chef and the author of “This Is Your Brain on Food,” who was not involved in the study, continued, “In nutritional psychiatry, balance is key and therefore consuming a well-rounded diet including ample amounts of fiber – particularly from sources like steel-cut oats, beans, lentils, and numerous other fruits and vegetables – can be part of a healthy lifestyle and prevention against cognitive decline in later years.
“While the study authors admit to limitations within the study, in my opinion, eating healthier has so many mental and physical health benefits that it’s a nutritional psychiatry no-brainer,” she added.
The study was partly supported by Health and Labour Science Research Grants for Dementia from the Ministry of Health, Labour and Welfare of Japan; JSPS Kakenhi; FULLHAP; and the Osaka University International Joint Research Promotion Programme with University College London. The authors and Dr. Naidoo report no relevant financial relationships.
A version of this article first appeared on Medscape.com.
FROM NUTRITIONAL NEUROSCIENCE
Long COVID patients may develop nerve damage: Study
according to a new study published in the journal Neurology: Neuroimmunology & Neuroinflammation (doi: 10.1212/NXI.0000000000001146).
The nerve damage, which has been seen even among mild coronavirus cases, appears to be caused by immunity problems triggered by infection.
“This is one of the early papers looking into causes of long COVID, which will steadily increase in importance as acute COVID wanes,” Anne Louise Oaklander, MD, the lead study author and a neurologist at Massachusetts General Hospital, Boston, said in a statement.
“Our findings suggest that some long COVID patients had damage to their peripheral nerve fibers and that damage to the small-fiber type of nerve cell may be prominent,” she said.
The research team analyzed data from 17 COVID-19 survivors with lingering symptoms who had no history or risks of neuropathy, or nerve damage or disease. The patients were from 10 states and territories, and all but one had mild infections.
They found that 10 patients – or 59% – had at least one test that confirmed neuropathy. Two patients had rare neuropathies that affected muscle nerves, and 10 were diagnosed with small-fiber neuropathy, which is a cause of chronic pain. Common symptoms included fatigue, weakness, changes in their senses, and pain in their hands and feet.
For treatment, 11 patients were given immunotherapies such as corticosteroids or intravenous immunoglobulins, and the five patients who received repeated IgG treatments appeared to benefit. Over time, 52% of patients improved, though none had all of their symptoms go away.
“Research from our team and others is clarifying what the different types of post-COVID neuropathy are and how best to diagnose and treat them,” she said. “Most long COVID neuropathies described so far appear to reflect immune responses to the virus that went off course.”
Dr. Oaklander noted that researchers haven’t been able to do clinical trials to evaluate specific post-COVID neuropathy treatments. But some existing treatments may help.
“Some patients seem to improve from standard treatments for other immune-related neuropathies,” she said.
A version of this article first appeared on WebMD.com.
according to a new study published in the journal Neurology: Neuroimmunology & Neuroinflammation (doi: 10.1212/NXI.0000000000001146).
The nerve damage, which has been seen even among mild coronavirus cases, appears to be caused by immunity problems triggered by infection.
“This is one of the early papers looking into causes of long COVID, which will steadily increase in importance as acute COVID wanes,” Anne Louise Oaklander, MD, the lead study author and a neurologist at Massachusetts General Hospital, Boston, said in a statement.
“Our findings suggest that some long COVID patients had damage to their peripheral nerve fibers and that damage to the small-fiber type of nerve cell may be prominent,” she said.
The research team analyzed data from 17 COVID-19 survivors with lingering symptoms who had no history or risks of neuropathy, or nerve damage or disease. The patients were from 10 states and territories, and all but one had mild infections.
They found that 10 patients – or 59% – had at least one test that confirmed neuropathy. Two patients had rare neuropathies that affected muscle nerves, and 10 were diagnosed with small-fiber neuropathy, which is a cause of chronic pain. Common symptoms included fatigue, weakness, changes in their senses, and pain in their hands and feet.
For treatment, 11 patients were given immunotherapies such as corticosteroids or intravenous immunoglobulins, and the five patients who received repeated IgG treatments appeared to benefit. Over time, 52% of patients improved, though none had all of their symptoms go away.
“Research from our team and others is clarifying what the different types of post-COVID neuropathy are and how best to diagnose and treat them,” she said. “Most long COVID neuropathies described so far appear to reflect immune responses to the virus that went off course.”
Dr. Oaklander noted that researchers haven’t been able to do clinical trials to evaluate specific post-COVID neuropathy treatments. But some existing treatments may help.
“Some patients seem to improve from standard treatments for other immune-related neuropathies,” she said.
A version of this article first appeared on WebMD.com.
according to a new study published in the journal Neurology: Neuroimmunology & Neuroinflammation (doi: 10.1212/NXI.0000000000001146).
The nerve damage, which has been seen even among mild coronavirus cases, appears to be caused by immunity problems triggered by infection.
“This is one of the early papers looking into causes of long COVID, which will steadily increase in importance as acute COVID wanes,” Anne Louise Oaklander, MD, the lead study author and a neurologist at Massachusetts General Hospital, Boston, said in a statement.
“Our findings suggest that some long COVID patients had damage to their peripheral nerve fibers and that damage to the small-fiber type of nerve cell may be prominent,” she said.
The research team analyzed data from 17 COVID-19 survivors with lingering symptoms who had no history or risks of neuropathy, or nerve damage or disease. The patients were from 10 states and territories, and all but one had mild infections.
They found that 10 patients – or 59% – had at least one test that confirmed neuropathy. Two patients had rare neuropathies that affected muscle nerves, and 10 were diagnosed with small-fiber neuropathy, which is a cause of chronic pain. Common symptoms included fatigue, weakness, changes in their senses, and pain in their hands and feet.
For treatment, 11 patients were given immunotherapies such as corticosteroids or intravenous immunoglobulins, and the five patients who received repeated IgG treatments appeared to benefit. Over time, 52% of patients improved, though none had all of their symptoms go away.
“Research from our team and others is clarifying what the different types of post-COVID neuropathy are and how best to diagnose and treat them,” she said. “Most long COVID neuropathies described so far appear to reflect immune responses to the virus that went off course.”
Dr. Oaklander noted that researchers haven’t been able to do clinical trials to evaluate specific post-COVID neuropathy treatments. But some existing treatments may help.
“Some patients seem to improve from standard treatments for other immune-related neuropathies,” she said.
A version of this article first appeared on WebMD.com.
FROM NEUROLOGY: NEUROIMMUNOLOGY & NEUROINFLAMMATION