Neurology

If you’ve ever felt an urge to scratch after witnessing someone else relieve their own itch, you’re certainly not alone. Itching can be contagious and the phenomenon is so common it doesn’t just affect humans. Now researchers may understand why.

Some background: In a 2007 study led by Zhou-Feng Chen, PhD, professor of anesthesiology, psychiatry, and developmental biology at the Washington University in St. Louis, researchers discovered a specific gene, the GRPR (gastrin-releasing peptide receptor), in the spinal cord and a corresponding neuropeptide, GRP (gastrin-releasing peptide). Together, the GRP system was found to transmit the “itch information” from one’s skin to the spinal cord.

This discovery was further backed by 2017 findings when Dr. Chen and his colleagues closely observed the molecular and neural basis of contagious itch behavior in mice. “We played a video that showed a mouse scratching at a very high frequency to other mice,” said Dr. Chen. “We found that, indeed, the mice who watched the video also scratched.”

To determine the inner workings at play, the researchers used molecular mapping to reveal increased neuronal activity in the suprachiasmatic nucleus (SCN), a bilateral structure found in the hypothalamus of the mouse’s brain. In other words, this part of the mouse’s brain “lit up” when a mouse displayed contagious scratching behavior.

The researchers then decided to take this one step further by manipulating the amount of GRP in the hypothalamus. “When we deleted the GRP in the SCN, the mice stopped imitating the scratch,” Dr. Chen said. “When we injected more GRP into the SCN, the mice started scratching like crazy.”

Now, after more investigating and research published in 2022 in Cell Reports, Dr. Chen and his team suspect contagious itching may have just as much to do with our eyeballs as our skin and spinal cord. Why? The phenomenon begins with a visual component: Someone seeing another person scratching.

The researchers targeted mice’s retinal ganglion cells, a type of light-capturing neuron found near the inner surface of the retina. When those cells were disabled, all scratching stopped.

This recent study argues that a previously undiscovered visual pathway may exist between the retina and the brain – bypassing the visual cortex – to provide more immediate physical reactions to potential adverse situations.

There’s more (and it could be quite relatable to some people): After the mice watched a video of another mouse scratching for half an hour, the researchers measured the mice’s stress hormone levels, finding a significant increase. This suggested that exposure to impulsive, contagious scratching behavior may have caused heightened anxiety in the mice.

“This is an important discovery that helps answer the psychological question of why animals and people scratch all the time,” said Dr. Chen. “We humans also scratch a lot, sometimes as a way to unconsciously express our internal anxiety.”

The mice may have interpreted the scratching video as a sudden negative change to their environment that they had to prepare for. “Contagious behavior is actually a very efficient way to inform other animals of what’s coming,” Dr. Chen said. “When we see other people running in a panic, there is no time to think. You just run as fast as you can. This is another example of contagious behavior that is in your own interest to survive.”

As a result, Dr. Chen believes it’s fair to infer that contagious behavior, including yawning and emotional contagion, is merely an expression of a fundamental survival mechanism that has evolved over time. “The human being is just an imitation machine. It’s often very difficult for people to act independently or as a minority because you would be working against evolution,” said Dr. Chen.

Scott Ira Krakower, DO, a child and adolescent psychiatrist at Northwell Health in Glen Oaks, N.Y., (and not party to this research), seconds this sentiment. “In regard to the physical benefits of contagion, it acts as a permanent defense and helps build collective immunity,” he said. “The social benefits when it comes to empathy or social media contagion are also important to our development. It helps us understand, adapt, and connect with others.”

Observing how empathy operates as a socially contagious behavior is something Dr. Chen and his colleagues are interested in looking into in the future.

“The definition of empathy is the sharing of emotions,” Dr. Chen said. “Shared feelings are crucial for social bonding and mental health, and for other animals, like mice, this is also the case.” Previous studies have shown that mice do, in fact, experience empathy and share feelings of pain and fear with one another.

There is still much to be explored in the study of contagious behaviors and the components of the brain that are activated during such behavior. Dr. Chen and his team intend to, ahem, scratch that particular itch.

A version of this article first appeared on Medscape.com.

If you’ve ever felt an urge to scratch after witnessing someone else relieve their own itch, you’re certainly not alone. Itching can be contagious and the phenomenon is so common it doesn’t just affect humans. Now researchers may understand why.

Some background: In a 2007 study led by Zhou-Feng Chen, PhD, professor of anesthesiology, psychiatry, and developmental biology at the Washington University in St. Louis, researchers discovered a specific gene, the GRPR (gastrin-releasing peptide receptor), in the spinal cord and a corresponding neuropeptide, GRP (gastrin-releasing peptide). Together, the GRP system was found to transmit the “itch information” from one’s skin to the spinal cord.

This discovery was further backed by 2017 findings when Dr. Chen and his colleagues closely observed the molecular and neural basis of contagious itch behavior in mice. “We played a video that showed a mouse scratching at a very high frequency to other mice,” said Dr. Chen. “We found that, indeed, the mice who watched the video also scratched.”

To determine the inner workings at play, the researchers used molecular mapping to reveal increased neuronal activity in the suprachiasmatic nucleus (SCN), a bilateral structure found in the hypothalamus of the mouse’s brain. In other words, this part of the mouse’s brain “lit up” when a mouse displayed contagious scratching behavior.

The researchers then decided to take this one step further by manipulating the amount of GRP in the hypothalamus. “When we deleted the GRP in the SCN, the mice stopped imitating the scratch,” Dr. Chen said. “When we injected more GRP into the SCN, the mice started scratching like crazy.”

Now, after more investigating and research published in 2022 in Cell Reports, Dr. Chen and his team suspect contagious itching may have just as much to do with our eyeballs as our skin and spinal cord. Why? The phenomenon begins with a visual component: Someone seeing another person scratching.

The researchers targeted mice’s retinal ganglion cells, a type of light-capturing neuron found near the inner surface of the retina. When those cells were disabled, all scratching stopped.

This recent study argues that a previously undiscovered visual pathway may exist between the retina and the brain – bypassing the visual cortex – to provide more immediate physical reactions to potential adverse situations.

There’s more (and it could be quite relatable to some people): After the mice watched a video of another mouse scratching for half an hour, the researchers measured the mice’s stress hormone levels, finding a significant increase. This suggested that exposure to impulsive, contagious scratching behavior may have caused heightened anxiety in the mice.

“This is an important discovery that helps answer the psychological question of why animals and people scratch all the time,” said Dr. Chen. “We humans also scratch a lot, sometimes as a way to unconsciously express our internal anxiety.”

The mice may have interpreted the scratching video as a sudden negative change to their environment that they had to prepare for. “Contagious behavior is actually a very efficient way to inform other animals of what’s coming,” Dr. Chen said. “When we see other people running in a panic, there is no time to think. You just run as fast as you can. This is another example of contagious behavior that is in your own interest to survive.”

As a result, Dr. Chen believes it’s fair to infer that contagious behavior, including yawning and emotional contagion, is merely an expression of a fundamental survival mechanism that has evolved over time. “The human being is just an imitation machine. It’s often very difficult for people to act independently or as a minority because you would be working against evolution,” said Dr. Chen.

Scott Ira Krakower, DO, a child and adolescent psychiatrist at Northwell Health in Glen Oaks, N.Y., (and not party to this research), seconds this sentiment. “In regard to the physical benefits of contagion, it acts as a permanent defense and helps build collective immunity,” he said. “The social benefits when it comes to empathy or social media contagion are also important to our development. It helps us understand, adapt, and connect with others.”

Observing how empathy operates as a socially contagious behavior is something Dr. Chen and his colleagues are interested in looking into in the future.

“The definition of empathy is the sharing of emotions,” Dr. Chen said. “Shared feelings are crucial for social bonding and mental health, and for other animals, like mice, this is also the case.” Previous studies have shown that mice do, in fact, experience empathy and share feelings of pain and fear with one another.

There is still much to be explored in the study of contagious behaviors and the components of the brain that are activated during such behavior. Dr. Chen and his team intend to, ahem, scratch that particular itch.

A version of this article first appeared on Medscape.com.

If you’ve ever felt an urge to scratch after witnessing someone else relieve their own itch, you’re certainly not alone. Itching can be contagious and the phenomenon is so common it doesn’t just affect humans. Now researchers may understand why.

Some background: In a 2007 study led by Zhou-Feng Chen, PhD, professor of anesthesiology, psychiatry, and developmental biology at the Washington University in St. Louis, researchers discovered a specific gene, the GRPR (gastrin-releasing peptide receptor), in the spinal cord and a corresponding neuropeptide, GRP (gastrin-releasing peptide). Together, the GRP system was found to transmit the “itch information” from one’s skin to the spinal cord.

This discovery was further backed by 2017 findings when Dr. Chen and his colleagues closely observed the molecular and neural basis of contagious itch behavior in mice. “We played a video that showed a mouse scratching at a very high frequency to other mice,” said Dr. Chen. “We found that, indeed, the mice who watched the video also scratched.”

To determine the inner workings at play, the researchers used molecular mapping to reveal increased neuronal activity in the suprachiasmatic nucleus (SCN), a bilateral structure found in the hypothalamus of the mouse’s brain. In other words, this part of the mouse’s brain “lit up” when a mouse displayed contagious scratching behavior.

The researchers then decided to take this one step further by manipulating the amount of GRP in the hypothalamus. “When we deleted the GRP in the SCN, the mice stopped imitating the scratch,” Dr. Chen said. “When we injected more GRP into the SCN, the mice started scratching like crazy.”

Now, after more investigating and research published in 2022 in Cell Reports, Dr. Chen and his team suspect contagious itching may have just as much to do with our eyeballs as our skin and spinal cord. Why? The phenomenon begins with a visual component: Someone seeing another person scratching.

The researchers targeted mice’s retinal ganglion cells, a type of light-capturing neuron found near the inner surface of the retina. When those cells were disabled, all scratching stopped.

This recent study argues that a previously undiscovered visual pathway may exist between the retina and the brain – bypassing the visual cortex – to provide more immediate physical reactions to potential adverse situations.

There’s more (and it could be quite relatable to some people): After the mice watched a video of another mouse scratching for half an hour, the researchers measured the mice’s stress hormone levels, finding a significant increase. This suggested that exposure to impulsive, contagious scratching behavior may have caused heightened anxiety in the mice.

“This is an important discovery that helps answer the psychological question of why animals and people scratch all the time,” said Dr. Chen. “We humans also scratch a lot, sometimes as a way to unconsciously express our internal anxiety.”

The mice may have interpreted the scratching video as a sudden negative change to their environment that they had to prepare for. “Contagious behavior is actually a very efficient way to inform other animals of what’s coming,” Dr. Chen said. “When we see other people running in a panic, there is no time to think. You just run as fast as you can. This is another example of contagious behavior that is in your own interest to survive.”

As a result, Dr. Chen believes it’s fair to infer that contagious behavior, including yawning and emotional contagion, is merely an expression of a fundamental survival mechanism that has evolved over time. “The human being is just an imitation machine. It’s often very difficult for people to act independently or as a minority because you would be working against evolution,” said Dr. Chen.

Scott Ira Krakower, DO, a child and adolescent psychiatrist at Northwell Health in Glen Oaks, N.Y., (and not party to this research), seconds this sentiment. “In regard to the physical benefits of contagion, it acts as a permanent defense and helps build collective immunity,” he said. “The social benefits when it comes to empathy or social media contagion are also important to our development. It helps us understand, adapt, and connect with others.”

Observing how empathy operates as a socially contagious behavior is something Dr. Chen and his colleagues are interested in looking into in the future.

“The definition of empathy is the sharing of emotions,” Dr. Chen said. “Shared feelings are crucial for social bonding and mental health, and for other animals, like mice, this is also the case.” Previous studies have shown that mice do, in fact, experience empathy and share feelings of pain and fear with one another.

There is still much to be explored in the study of contagious behaviors and the components of the brain that are activated during such behavior. Dr. Chen and his team intend to, ahem, scratch that particular itch.

A version of this article first appeared on Medscape.com.

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Social isolation in older individuals has been linked to reduced brain volume in regions associated with memory, a new study shows.

Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.

“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.

The study was published online in Neurology.
 

A dementia prevention strategy

Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.

In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
 

Lower brain volume

Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.

White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.

Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).

The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.

Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
 

Worse physical health

The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.

“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.

Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.

“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”

He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that  isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.

“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.

The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.

A version of this article first appeared on Medscape.com.

Social isolation in older individuals has been linked to reduced brain volume in regions associated with memory, a new study shows.

Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.

“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.

The study was published online in Neurology.
 

A dementia prevention strategy

Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.

In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
 

Lower brain volume

Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.

White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.

Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).

The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.

Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
 

Worse physical health

The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.

“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.

Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.

“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”

He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that  isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.

“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.

The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.

A version of this article first appeared on Medscape.com.

Social isolation in older individuals has been linked to reduced brain volume in regions associated with memory, a new study shows.

Further, the association between social isolation and reduced brain volume appears to be at least partly mediated by depressive symptoms.

“We believe that efforts should be made to reduce social isolation among the elderly as much as possible,” investigator Toshiharu Ninomiya, MD, PhD, professor of epidemiology and public health at Kyushu University in Fukuoka, Japan, said in an interview.

The study was published online in Neurology.
 

A dementia prevention strategy

Dr. Ninomiya noted there have been several studies suggesting that social interaction is beneficial in preventing cognitive decline and the onset of dementia.

In addition, recent epidemiological studies have shown social isolation is associated with a risk for cognitive decline and dementia.

Although the investigators note that very little is known about the link between the two, some studies have shown that social isolation is linked with depressive symptoms in older adults, and late-life depression has been associated with brain atrophy.

To explore the potential link between social isolation and brain atrophy, as well as the role of depression as a potential mediator, the investigators studied nearly 9,000 citizens aged 65 and older as part of the Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD), an ongoing, community-based nationwide cohort study of dementia in Japan.

Participants were recruited from eight research sites across Japan, and each had a baseline MRI scan between 2016 and 2018. The investigators excluded those with a dementia diagnosis at baseline. Self-reported frequency of social contact was categorized as every day, several times a week, several times a month, or seldom.

Participants also answered questions about medical history and treatment, antihypertensive or antidiabetic medications, exercise, current alcohol intake, and smoking habits. Depressive symptoms were assessed with the Geriatric Depression Scale. Of the participants, 57% were women, and the mean age was 73 years.
 

Lower brain volume

Total brain volume was lower in those with the lowest frequency of social contact vs. those with the highest frequency (67.3% vs. 67.8%). Less social contact was also linked to smaller temporal lobe, occipital lobe, cingulum, hippocampus, and amygdala volumes.

White matter lesion volume increased with fewer social interactions, from 0.26% in the most social group to 0.30% in the least.

Cognitive function was higher in participants who had daily social contact, compared with those who had the least contact (28 vs. 27 on the Mini-Mental State Examination; P < .001). Scores between 25 and 30 are considered normal.

Depressive symptoms were lower in the daily contact group, compared with the seldom-contact group (P < .001).

The team also found that lower frequency of social contact was significantly associated with the smaller superior, middle, or inferior temporal gyrus; and a smaller fusiform gyrus, transverse temporal gyrus, temporal pole, and entorhinal cortex, among other subregions.

Mediation analyses indicated that depressive symptoms accounted for only 15%-29% of the associations of lower frequency of social contact with each regional volume.
 

Worse physical health

The results also showed that socially isolated participants were more likely to have diabetes, to have hypertension, to smoke, and to be physically inactive.

“Cardiovascular risk factors have been reported to cause endothelial dysfunction in the brain, which could in turn lead to problems in maintaining microcirculation and blood-brain barrier function,” the investigators write.

Some epidemiological studies have associated cardiovascular risk factors with brain atrophy, they noted, which could have been one of the underlying mechanisms.

Another possibility is that reduced cognitive stimulation due to social isolation may cause brain atrophy, they add.

“Ultimately,” Dr. Ninomiya said, “the detailed mechanism of the relationship between social isolation and brain volume is not yet clear.”

He also said more research is needed to know whether the findings would apply to people in other countries.

In an accompanying editorial, Alexa Walter, PhD, and Danielle Sandsmark, MD, PhD, from the University of Pennsylvania, Philadelphia, note that  isolation has been associated with many adverse health outcomes, including increased risk of heart disease, stroke, and premature death.

“Given these findings, future work considering social health factors in the context of neurological disease is an important area of research to consider. Additionally, leveraging other existing longitudinal studies could provide us with an opportunity to better understand these relationships within populations and inform public policy to address these issues,” Dr. Walter and Dr. Sandsmark write.

The study was funded by the Japan Agency for Medical Research and Development and Suntory Holdings Limited. Dr. Ninomiya reports receiving grants from Suntory Holdings Limited.

A version of this article first appeared on Medscape.com.

With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.

To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.

Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
 

Managing patient and family expectations

These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.

In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.

But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
 

Only a sliver of Alzheimer’s patients are current candidates

The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.

Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.

Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.
 

Significant risks

Antiamyloid drugs are well-known to cause serious side effects. In the lecanemab trial, 13% of participants receiving Leqembi experienced brain swelling (vs. 2% of participants receiving placebo) and 17% of participants had brain bleeding (vs. 9% of participants on placebo). In the donanemab trial, brain bleeding occurred in 31.4% of participants on the drug (vs. 13.6% on placebo) and swelling occurred in 24% (vs. 2.1% receiving placebo). Thankfully, in both trials, most of these adverse events did not produce significant symptoms, but in rare cases these events caused severe or catastrophic neurologic injury, including death.

How can we best guide patients and their families to weigh the uncertain benefits against potentially serious risks? We can start by considering the patient characteristics most likely to portend increased risk for serious side effects: apo E4 mutations, blood thinner use, and the presence of microhemorrhages on brain imaging. But after that, we’re left with a lot of uncertainty in terms of which patients are most likely to see meaningful clinical improvements from the drug and unknown factors that may increase the risks of treatment.
 

A costly therapy

Medicare plans to cover 80% of lecanemab’s steep cost of $26,500 per year. Still, that will leave many patients with a hefty copay, potentially over $6,000 per year. But that only scratches the surface. Consider the frequent medical visits, repeated brain scans, laboratory tests, and infusion center appointments. It’s been estimated that all-in, the treatment will actually cost about $90,000 per year.

Yes, Medicare will reimburse a large portion of that cost, but it adds up to an estimated $2 billion per year for about 85,000 patients. This will probably spur increases to Medicare premiums, among other economic consequences for the health care system.

We’ll probably have to wait for an FDA approval decision before we know where donanemab will be priced.
 

Logistical challenges could be a rate-limiting step

Ask anyone who’s tried to see a neurologist recently, and they’ll tell you that the wait for a new patient appointment is months long. The shortage of neurologists in the United States is already a crisis, and there are even fewer cognitive neurologists. How long will patients be forced to wait for their diagnosis?

Many geriatricians will get comfortable prescribing these drugs, but will our already overburdened primary care providers have the bandwidth to do the same? It’s a tall order.

A new world of Alzheimer’s treatments also means that the infrastructure of our health care systems will need to be ramped up. Lecanemab infusions are administered every 2 weeks and donanemab every 4 weeks. Infusion centers will need to accommodate a lot more patients. And those patients will need frequent brain scans, so neuroimaging centers will need to increase their capacity to perform many more brain MRI and PET scans.
 

Antiamyloid drugs: An exciting first step

The bottom line is that these drugs aren’t the Alzheimer’s holy grail: An accessible treatment that could stop the disease in its tracks or reverse cognitive impairment. They are, however, a very promising breakthrough.

Yes, there are a ton of kinks to work out here, but this is an exciting start. Alzheimer’s research is entering a renaissance era that will hopefully bring more groundbreaking developments. Better biomarkers to facilitate faster, easier diagnosis. More drugs that go beyond amyloid proteins for their therapeutic targets. Treatments for later-stage disease. Drugs that prevent dementia altogether.

Ultimately, these new antiamyloid beta drugs are an exciting indication that we will eventually have a toolkit of Alzheimer’s drugs to choose from. For now, we’ve taken a solid step forward and there is ample reason to be hopeful for the future.

Dr. Croll is assistant professor of neurology at Temple University, Philadelphia. She reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.

To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.

Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
 

Managing patient and family expectations

These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.

In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.

But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
 

Only a sliver of Alzheimer’s patients are current candidates

The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.

Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.

Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.
 

Significant risks

Antiamyloid drugs are well-known to cause serious side effects. In the lecanemab trial, 13% of participants receiving Leqembi experienced brain swelling (vs. 2% of participants receiving placebo) and 17% of participants had brain bleeding (vs. 9% of participants on placebo). In the donanemab trial, brain bleeding occurred in 31.4% of participants on the drug (vs. 13.6% on placebo) and swelling occurred in 24% (vs. 2.1% receiving placebo). Thankfully, in both trials, most of these adverse events did not produce significant symptoms, but in rare cases these events caused severe or catastrophic neurologic injury, including death.

How can we best guide patients and their families to weigh the uncertain benefits against potentially serious risks? We can start by considering the patient characteristics most likely to portend increased risk for serious side effects: apo E4 mutations, blood thinner use, and the presence of microhemorrhages on brain imaging. But after that, we’re left with a lot of uncertainty in terms of which patients are most likely to see meaningful clinical improvements from the drug and unknown factors that may increase the risks of treatment.
 

A costly therapy

Medicare plans to cover 80% of lecanemab’s steep cost of $26,500 per year. Still, that will leave many patients with a hefty copay, potentially over $6,000 per year. But that only scratches the surface. Consider the frequent medical visits, repeated brain scans, laboratory tests, and infusion center appointments. It’s been estimated that all-in, the treatment will actually cost about $90,000 per year.

Yes, Medicare will reimburse a large portion of that cost, but it adds up to an estimated $2 billion per year for about 85,000 patients. This will probably spur increases to Medicare premiums, among other economic consequences for the health care system.

We’ll probably have to wait for an FDA approval decision before we know where donanemab will be priced.
 

Logistical challenges could be a rate-limiting step

Ask anyone who’s tried to see a neurologist recently, and they’ll tell you that the wait for a new patient appointment is months long. The shortage of neurologists in the United States is already a crisis, and there are even fewer cognitive neurologists. How long will patients be forced to wait for their diagnosis?

Many geriatricians will get comfortable prescribing these drugs, but will our already overburdened primary care providers have the bandwidth to do the same? It’s a tall order.

A new world of Alzheimer’s treatments also means that the infrastructure of our health care systems will need to be ramped up. Lecanemab infusions are administered every 2 weeks and donanemab every 4 weeks. Infusion centers will need to accommodate a lot more patients. And those patients will need frequent brain scans, so neuroimaging centers will need to increase their capacity to perform many more brain MRI and PET scans.
 

Antiamyloid drugs: An exciting first step

The bottom line is that these drugs aren’t the Alzheimer’s holy grail: An accessible treatment that could stop the disease in its tracks or reverse cognitive impairment. They are, however, a very promising breakthrough.

Yes, there are a ton of kinks to work out here, but this is an exciting start. Alzheimer’s research is entering a renaissance era that will hopefully bring more groundbreaking developments. Better biomarkers to facilitate faster, easier diagnosis. More drugs that go beyond amyloid proteins for their therapeutic targets. Treatments for later-stage disease. Drugs that prevent dementia altogether.

Ultimately, these new antiamyloid beta drugs are an exciting indication that we will eventually have a toolkit of Alzheimer’s drugs to choose from. For now, we’ve taken a solid step forward and there is ample reason to be hopeful for the future.

Dr. Croll is assistant professor of neurology at Temple University, Philadelphia. She reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

With the Food and Drug Administration’s full stamp of approval in hand, Leqembi (lecanemab) is poised to catapult us into a new era of treatment for Alzheimer’s disease. And now that the donanemab trial data are out, there’s another antiamyloid drug waiting in the wings.

To finally have true disease-modifying therapies for Alzheimer’s disease is a massive step forward for a field that’s been plagued with disappointment. But these drugs come with serious concerns and unknowns. They will require complex decision-making, putting doctors, patients, and their families in a medical quandary.

Striking the right balance between cautious optimism and realistic expectations will be a formidable challenge.
 

Managing patient and family expectations

These drugs are no magic bullet. They slow down the dementia’s progression, buying patients more time (on the order of months) before they begin to experience significant worsening. We’ll need a lot more information from research and clinical experience before we can understand how meaningful that treatment effect is. Right now, it is unclear whether eligible patients and their families will even perceive tangible differences.

In the CLARITY-AD trial, participants on lecanemab experienced a 27% slowing in the rate of cognitive decline over 18 months. Donanemab was shown to slow decline in memory and cognition by about 35% over the same time frame in the TRAILBLAZER-ALZ 2 trial. That translates to more time for patients and their families to enjoy independence, maintain normal life, and stave off the most distressing parts of the disease.

But what happens after 18 months of treatment – will the treatment effect magnify or dissipate? How much time are we really buying in the long run? Counseling patients and their families is made all the more difficult when the answers to important questions like these remain to be seen.
 

Only a sliver of Alzheimer’s patients are current candidates

The fact is that most patients living with Alzheimer’s disease will not qualify for treatment with these drugs. Lecanemab is approved for people with early-stage disease, meaning their dementia is mild or they have mild cognitive impairment, which is a precursor to full-blown Alzheimer’s disease. Of the 6 million people in the United States living with Alzheimer’s, about 1.5 million are estimated to fall into that category. We can expect to see a similar qualifier for donanemab if it receives FDA approval, especially because that trial suggested a more pronounced treatment effect for patients in the earliest stages of the disease.

Even if a patient hits the sweet spot where they have just enough cognitive impairment, but not too much, they aren’t technically therapeutic candidates until prerequisite testing confirms amyloid protein accumulation in the brain via PET scan or cerebrospinal fluid analysis.

Even then, the FDA’s boxed warning for lecanemab recommends that patients undergo genetic testing for the apo E4 mutation to identify those at a particularly high risk for severe adverse effects including brain bleeding and swelling. This recommendation is not unreasonable considering that 15% of the Alzheimer’s population has two copies of the apo E4 mutation and fall into that high-risk group.
 

Significant risks

Antiamyloid drugs are well-known to cause serious side effects. In the lecanemab trial, 13% of participants receiving Leqembi experienced brain swelling (vs. 2% of participants receiving placebo) and 17% of participants had brain bleeding (vs. 9% of participants on placebo). In the donanemab trial, brain bleeding occurred in 31.4% of participants on the drug (vs. 13.6% on placebo) and swelling occurred in 24% (vs. 2.1% receiving placebo). Thankfully, in both trials, most of these adverse events did not produce significant symptoms, but in rare cases these events caused severe or catastrophic neurologic injury, including death.

How can we best guide patients and their families to weigh the uncertain benefits against potentially serious risks? We can start by considering the patient characteristics most likely to portend increased risk for serious side effects: apo E4 mutations, blood thinner use, and the presence of microhemorrhages on brain imaging. But after that, we’re left with a lot of uncertainty in terms of which patients are most likely to see meaningful clinical improvements from the drug and unknown factors that may increase the risks of treatment.
 

A costly therapy

Medicare plans to cover 80% of lecanemab’s steep cost of $26,500 per year. Still, that will leave many patients with a hefty copay, potentially over $6,000 per year. But that only scratches the surface. Consider the frequent medical visits, repeated brain scans, laboratory tests, and infusion center appointments. It’s been estimated that all-in, the treatment will actually cost about $90,000 per year.

Yes, Medicare will reimburse a large portion of that cost, but it adds up to an estimated $2 billion per year for about 85,000 patients. This will probably spur increases to Medicare premiums, among other economic consequences for the health care system.

We’ll probably have to wait for an FDA approval decision before we know where donanemab will be priced.
 

Logistical challenges could be a rate-limiting step

Ask anyone who’s tried to see a neurologist recently, and they’ll tell you that the wait for a new patient appointment is months long. The shortage of neurologists in the United States is already a crisis, and there are even fewer cognitive neurologists. How long will patients be forced to wait for their diagnosis?

Many geriatricians will get comfortable prescribing these drugs, but will our already overburdened primary care providers have the bandwidth to do the same? It’s a tall order.

A new world of Alzheimer’s treatments also means that the infrastructure of our health care systems will need to be ramped up. Lecanemab infusions are administered every 2 weeks and donanemab every 4 weeks. Infusion centers will need to accommodate a lot more patients. And those patients will need frequent brain scans, so neuroimaging centers will need to increase their capacity to perform many more brain MRI and PET scans.
 

Antiamyloid drugs: An exciting first step

The bottom line is that these drugs aren’t the Alzheimer’s holy grail: An accessible treatment that could stop the disease in its tracks or reverse cognitive impairment. They are, however, a very promising breakthrough.

Yes, there are a ton of kinks to work out here, but this is an exciting start. Alzheimer’s research is entering a renaissance era that will hopefully bring more groundbreaking developments. Better biomarkers to facilitate faster, easier diagnosis. More drugs that go beyond amyloid proteins for their therapeutic targets. Treatments for later-stage disease. Drugs that prevent dementia altogether.

Ultimately, these new antiamyloid beta drugs are an exciting indication that we will eventually have a toolkit of Alzheimer’s drugs to choose from. For now, we’ve taken a solid step forward and there is ample reason to be hopeful for the future.

Dr. Croll is assistant professor of neurology at Temple University, Philadelphia. She reported no relevant conflicts of interest.

A version of this article first appeared on Medscape.com.

Meditation and foreign language training does not boost cognitive function in cognitively healthy older adults, a new study suggests.

The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.

“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online  in JAMA Network Open.

Harriet Demnitz-King

Contradictory findings

For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.

The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.

Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.

The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.

“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”

Natalie Marchant

More to learn

The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.

Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.

“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”

Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.

“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”

The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.

A version of this article first appeared on Medscape.com.

Meditation and foreign language training does not boost cognitive function in cognitively healthy older adults, a new study suggests.

The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.

“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online  in JAMA Network Open.

Harriet Demnitz-King

Contradictory findings

For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.

The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.

Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.

The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.

“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”

Natalie Marchant

More to learn

The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.

Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.

“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”

Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.

“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”

The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.

A version of this article first appeared on Medscape.com.

Meditation and foreign language training does not boost cognitive function in cognitively healthy older adults, a new study suggests.

The findings are similar to results from another study published last year but are contrary to previous findings showing cognitive benefits for practicing meditation and learning a new language later in life.

“Based on existing literature, which has provided support for the efficacy of meditation and foreign language training in promoting cognition among older adults, perhaps the most surprising outcome of our study was the lack of evidence indicating cognitive benefits after 18 months of either intervention,” lead author Harriet Demnitz-King, MSc, a doctoral candidate at University College London, said in an interview. The findings were published online  in JAMA Network Open.

Harriet Demnitz-King

Contradictory findings

For the study, 135 French-speaking, cognitively healthy people were randomized to English-language training, meditation, or a control group. All participants were aged 65 years or older, had been retired for at least 1 year, and had completed at least 7 years of education.

The meditation and English-language training interventions were both 18 months long and included a 2-hour weekly group session, daily home practice of at least 20 minutes, and 1-day intensive 5-hour practice.

Researchers found no significant changes in global cognition, episodic memory, executive function, or attention with either intervention, compared with the control group or to each other.

The findings contradict the researchers’ earlier work that found mindfulness meditation boosted cognitive function in older adults with subjective cognitive decline.

“We are still trying to reconcile these findings,” senior author Natalie Marchant, PhD, associate professor in the division of psychiatry at University College London, said. “It may be that mindfulness meditation may not improve cognition beyond normally functioning levels but may help to preserve cognition in the face of cognitive decline.”

Natalie Marchant

More to learn

The results harken to those of a study last year with a similar participant group and similar results. In that work, mindfulness meditation and exercise also failed to boost cognition in healthy adults. But that may not be the whole story, according to Eric Lenze, MD, professor and chair of psychiatry at Washington University School of Medicine, St. Louis.

Dr. Lenze was a lead author on that earlier research, known as the MEDEX trial, but was not involved with this study. He commented on the new findings for this news organization.

“People may read these results, and ours that were published in JAMA in December, as suggesting that lifestyle and cognitive interventions don’t work in older adults, but that’s not what this shows, in my opinion,” Dr. Lenze said. “It shows that we don’t understand the science of the aging brain as much as we would like to.”

Participants in most of these studies were mostly White, highly educated, and in good cognitive health, all characteristics that could have skewed these findings, he added.

“It may be that interventions to improve cognitive function in older adults would be more likely to help people who have more room to benefit,” Dr. Lenze said. “If you’re already highly educated, healthy, and cognitively normal, why should we expect that you could do even better than that?”

The Age-Well study was funded by European Union in Horizon 2020 program and Inserm, Région Normandie, Fondation d’entreprise MMA des Entrepreneurs du Futur. Dr. Marchant reports grants from Alzheimer’s Society and the U.K. Medical Research Council. Dr. Lenze reports funding from Takeda pharmaceuticals and has been a consultant for Pritikin Intensive Cardiac Rehabilitation.

A version of this article first appeared on Medscape.com.

Initiating treatment for multiple sclerosis (MS) within 6 months of the first symptoms is associated with a significantly lower risk for severe disability 1 decade later, a new study suggests.

Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.

Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.

“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.

The findings were published online in Neurology.
 

Measuring disability

The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).

The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.

MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.

Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.

Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).

The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
 

Better disease stability

The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).

The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.

The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.

Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.

Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.

“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.

“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.

He added that very early treatment after first symptoms is key to preserving neurologic functionality.
 

Controversy remains

Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.

“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.

Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.

“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”

The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.

A version of this article first appeared on Medscape.com.

Initiating treatment for multiple sclerosis (MS) within 6 months of the first symptoms is associated with a significantly lower risk for severe disability 1 decade later, a new study suggests.

Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.

Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.

“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.

The findings were published online in Neurology.
 

Measuring disability

The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).

The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.

MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.

Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.

Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).

The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
 

Better disease stability

The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).

The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.

The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.

Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.

Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.

“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.

“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.

He added that very early treatment after first symptoms is key to preserving neurologic functionality.
 

Controversy remains

Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.

“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.

Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.

“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”

The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.

A version of this article first appeared on Medscape.com.

Initiating treatment for multiple sclerosis (MS) within 6 months of the first symptoms is associated with a significantly lower risk for severe disability 1 decade later, a new study suggests.

Patients who received early treatment had a 45% lower risk of reaching a disability score of 3 and a 60% lower risk of advancing to secondary progressive MS compared with those who began treatment 18 months or more after symptoms presented.

Those with a score of 3 can still walk unassisted but have moderate disability in one of eight areas, such as motor function, vision or thinking skills, or mild disability in three or four areas.

“With a very early treatment, within 6 months from the first symptoms and even before the MS diagnosis, we are now able to decrease long-term disability. This means the earlier the better – time is brain,” lead author Alvaro Cobo-Calvo, MD, PhD, clinical neurologists and researcher with the Multiple Sclerosis Center of Catalonia in Barcelona and the Universitat Autonoma de Barcelona, said in an interview.

The findings were published online in Neurology.
 

Measuring disability

The observational, retrospective study included people aged 50 years or younger who received MS treatment within 6 months of their first clinical demyelinating event (n = 194), 6-16 months later (n = 192), or more than 16 months after the initial symptoms presented (n = 194).

The investigators noted that this cohort is one of the few that is considered “deeply phenotyped,” meaning it is followed prospectively over time with strict quality controls and systematic data collection methods.

MRIs were done within 3-5 months of the first symptoms, again at 12 months after the first event, and every 5 years over a median 11.2-year follow-up.

Disability levels were measured using the Expanded Disability Status Scale, with scores ranging from 0-10 and higher scores indicating more disability.

Patients who received treatment within 6 months of first symptoms were 45% less likely to have a disability score of 3 by the end of the study than did those who received treatment more than 16 months after that first event (hazard ratio, 0.55; 95% confidence interval, 0.32-0.97).

The earliest-treatment group also had a 60% lower risk of advancing to secondary progressive MS than did people in the latest-treatment group (HR, 0.40; 95% CI, 0.19-0.85).
 

Better disease stability

The researchers also found that earlier treatment was associated with a 53% better chance of disease stability 1 year after initial treatment (HR, 0.47; 95% CI, 0.28-0.80).

The early-treatment group also had a lower disability progression rate and lower severe disability in a self-reported test, compared with those who were treated later.

The investigators also found that patients who received early treatment were at lower risk for disability, even those with a higher baseline radiologic burden.

Current guidelines recommend early treatment of MS, but it is unclear whether disease-modifying treatments (DMTs) should be prescribed after the first MS symptoms or after a definitive MS diagnosis.

Earlier studies often evaluated treatment efficacy after MS diagnosis. This study began tracking efficacy when therapy began after the first symptoms. In some cases, that was before a diagnosis was given.

“It is important to be cautious when starting treatment and we need to know if the patient will evolve to MS or if the patient is diagnosed with MS based on current McDonald criteria.

“In our study, 70% of patients had MS at the time of the first symptoms according to McDonald 201, but the remainder started treatment without an ‘official’ diagnosis but with an event highly suggestive of MS,” Dr. Cobo-Calvo said.

He added that very early treatment after first symptoms is key to preserving neurologic functionality.
 

Controversy remains

Adding MRI results as a clinical variable is a novel approach, but the MRI risk score used in the study is a new tool that has not yet been validated, the authors of an accompanying editorial noted.

“The results of this study show that in order to achieve a balance between compared groups, matching on MRI has little to add to good-quality balancing on patients’ clinical and demographic features,” wrote Erin Longbrake, MD, PhD, of the department of neurology, Yale University, New Haven, Conn., and Tomas Kalincik, MD, PhD, of the Neuroimmunology Centre, department of neurology, Royal Melbourne Hospital and the CORe unit, department of medicine, University of Melbourne.

Despite growing evidence pointing to improved outcomes from administering DMTs soon after diagnosis, the timing and sequence of therapy remains an area of controversy, they added.

“While these uncertain diagnostic scenarios may tempt neurologists to ‘wait and see,’ the data presented here remind us that these patients remain at risk of accumulating disability,” the authors wrote. “Neurologists must therefore remain vigilant to ensure that diagnosis is made promptly, that patients are followed up effectively and that effective treatments are used liberally.”

The study was funded by the European Regional Development Fund, Instituto de Salud Carlos III. Dr. Cobo-Calvo has received a grant from Instituto de Salud Carlos III. Dr. Longbrake has consulted for Genentech and NGM Bio and received research support from Biogen & Genentech. Dr. Kalincik has received conference travel support and/or speaker honoraria from WebMD Global, Eisai, Novartis, Biogen, Roche, Sanofi Genzyme, Teva, BioCSL, and Merck, and has received research or educational event support from Biogen, Novartis, Genzyme, Roche, Celgene, and Merck.

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

On July 13, the Food and Drug Administration approved the first over-the-counter (OTC) norgestrel birth control pill (Opill). The daily oral contraceptive was approved for prescription use 5 decades ago, providing regulators with a half-century of data to show that the progestin-only drug can be used safely without a prescription. 

The drug is the latest in a series of medications that have made the switch from behind the pharmacy counter to retail shelves. 

Experts say several more classes of drugs to treat high cholesterol, asthma, and other common health problems could be next.
 

Why switch?

When a drug manufacturer submits a proposal for a switch to OTC, the key question that the FDA considers is patient safety. Some risks can be mitigated by approving OTC drugs at lower doses than what is available as the prescription version. 

“There is no drug that doesn’t have risks,” said Almut G. Winterstein, RPh, PhD, a distinguished professor in pharmaceutical outcomes and policy and director of the Center for Drug Evaluation and Safety at the University of Florida, Gainesville. “Risks are mitigated by putting specific constraints around access to those medications.”

Dr. Winterstein, a former chair of the FDA’s Drug Safety and Risk Management Advisory Committee, said that nonprescription drugs are unnecessary in a functional health care system. 

Many patients may struggle with accessing health clinicians, so making medications available OTC fills gaps left by not being able to get a prescription, according to Dr. Winterstein. 

A 2012 paper funded by the Consumer Healthcare Products Association (CHPA), the organization representing manufacturers and distributors of OTC medications, estimated that one quarter of people who bought OTC drugs would not otherwise seek treatment if these treatments were available only via prescription. The CHPA notes that the number of those who experience allergies who use nonprescription antihistamines and allergy-relief drugs increased by about 10% between 2009 and 2015. 
 

Cholesterol drugs

Approximately 80 million U.S. adults are eligible for cholesterol-lowering medications, particularly statins, but nearly half don’t take them, according to the Centers for Disease Control and Prevention. 

Fear of side effects is the most common reason people might avoid taking these drugs. But eliminating the need for a refill may encourage uptake of the statins. 

“It’s refill, refill, refill,” said Allen J. Taylor, MD, chairman of cardiology at MedStar Heart and Vascular Institute, in Washington. “We spend a ton of time refilling statins and it’s a headache for patients, too.” 

The need to secure regular prescriptions for the drug, “doesn’t put enough trust and faith in pharmacists and doesn’t put enough trust and faith in patients,” Dr. Taylor said. 

Moving statins to the front end of a pharmacy might not be the best move given the potential for drug interactions, but a nonprescription behind-the-counter approach could work, according to Dr. Taylor. 

“The concerns are modest at most, to where they can be monitored by a pharmacist,” he said. “There’s probably more people that would take a statin if they had that kind of access.” 

Many statin manufacturers have attempted to make the prescription-to-OTC switch. In 2005, an FDA advisory panel rejected Merck’s proposal for OTC sales of lovastatin after reviewing a study that found only 55% of OTC purchases would have been medically appropriate. 

In 2015, Pfizer pulled its application to make the cholesterol drug atorvastatin available to patients OTC because patients were not using the drug correctly. AstraZeneca is investigating an online platform that would allow patients to self-assess their eligibility for rosuvastatin. 
 

Asthma inhalers 

Inhalers are the main rescue therapy for asthma aside from a visit to the ED. 

The only inhaler available OTC is epinephrine sold under the brand name Primatene Mist, but this type of medicine device is not recommended as a first-line therapy for acute asthma symptoms, according to the American Medical Association. 

“It’s been around for a long time and has stayed over the counter even though newer, safer agents have come onto the market which aren’t available over the counter,” said William B. Feldman, MD, DPhil, MPH, a pulmonologist at Brigham and Women’s Hospital, Boston. 

Patients who have a hard time getting to a doctor or patients who lack insurance often face barriers accessing albuterol inhalers and beta agonist–corticosteroid combinations, according to Dr. Feldman. A switch to OTC distribution would widen access. 

“What we’re advocating is, if they’re going to have access to Primatene Mist, wouldn’t it be sensible to have access to a safer and more effective therapy?” Dr. Feldman said. 
 

Triptans

Migraines affect an estimated 39 million people in the United States, according to the American Migraine Foundation. Several drugs to treat migraine are available OTC, including nonsteroidal anti-inflammatory drugs, aspirin, and acetaminophen. Triptans, drugs used for the short-term treatment of acute symptoms, are prescription-only in the United States. 

But in the United Kingdom, triptans first became available in retail stores in 2006, leading to reduced costs for patients, employers, and the government. One study found that government health expenditures would be reduced by $84 million annually if the OTC switch were made in six European countries. 

However, overuse of the drug and potential contraindications have been cited as concerns with OTC access. 

For Dr. Winterstein, the decision to switch isn’t just about the freedom to buy a drug; it comes down to weighing potential risks and benefits. 

“Drugs are only as good as if they’re used in the context of how they should be used,” Dr. Winterstein said. “It’s not candy.”
 

A version of this article first appeared on Medscape.com.

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Treatment with an experimental oral tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), led to a statistically significant reduction in an established biomarker of neurodegeneration in Alzheimer’s disease (AD) in the LUCIDITY phase 3 trial.
 

Blood concentrations of neurofilament light chain (NfL) showed a 93% reduction in change over 12 months in participants receiving HMTM at the target dose of 16 mg/day relative to the control group, which correlated significantly with a tau biomarker (p-tau 181) in blood and changes in cognitive test scores.

“This is the first tau aggregation inhibitor to reach the phase 3 stage of development and to produce results like this,” Claude Wischik, PhD, executive chairman of TauRx Therapeutics, which is developing the drug, noted in an interview.

“NfL is one of the best studied biomarkers in the business because it goes off the rails in a range of neurodegenerative disorders. In AD, it correlates with disease severity, and it tracks ongoing damage to neurons,” Dr. Wischik explained.

Oral HMTM was designed to reduce tau pathology in AD, and the noted changes in NfL concentration by HMTM indicate a “direct impact on disease pathology,” Dr. Wischik said.

The findings, from a prespecified blood biomarker analysis of the LUCIDITY phase 3 trial, were presented at the annual Alzheimer’s Association International Conference.
 

Support for tau inhibitor

Topline results from the LUCIDITY trial showed improvement in cognition over 18 months in participants with mild cognitive impairment (MCI) caused by AD who were treated with a 16-mg/day dose of HMTM.

However, in an odd twist, participants in the control group who received a low dose of methylthioninium chloride (MTC) also showed cognitive improvement.

As a result, HMTM 16 mg/day failed to reach its two primary endpoints – change from baseline on the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog11) and the Alzheimer’s Disease Cooperative Study/Activities of Daily Living Inventory (ADCS-ADL23) – relative to the MTC control group.

That’s likely because treatment with MTC, which is a variant of HMTM, unexpectedly achieved blood levels of active drug above the threshold needed to produce a clinical effect.

For the prespecified biomarker analysis reported at AAIC 2023, baseline and 12-month NfL plasma levels were available in 161 of 185 participants receiving HMTM 16 mg/day, 38 of 48 receiving HMTM 8 mg/day and 136 of 185 receiving MTC 8 mg/week.

Blood concentrations of NfL showed a statistically significant 93% reduction in change over 12 months in participants receiving HMTM at a dose of 16 mg/day relative to the control group (P = .0278), Dr. Wischik reported.

In addition, the p-tau 181 increase over 12 months “reduced to zero” with HMTM 16 mg/day and there was significant correlation between change in NfL and p-tau 181 concentration, he noted.

NfL reductions were significantly correlated with change in ADAS-Cog11 (P = .0038) and whole brain volume (P = .0359) over 24 months.
 

‘Exciting’ biomarker data

Commenting on the new data in an interview, Christopher Weber, PhD, director of global science initiatives at the Alzheimer’s Association, said the phase 3 LUCIDITY results “suggest that HMTM could be a potential therapeutic for slowing down neurodegenerative processes in Alzheimer’s disease.”

“Plasma NfL is an interesting biomarker which is used more and more in clinical trials because it’s noninvasive, accessible, and can assist in diagnosing and monitoring the disease in the early stages. Elevated NfL levels suggest that neurons are being affected in the brain, which could indicate the presence or progression of Alzheimer’s disease,” Dr. Weber said in an interview.

He said the biomarker data from the LUCIDITY study are “exciting.”

“However, due to the relatively small sample size, we look forward to seeing additional research on HMTM in larger, and even more diverse cohorts to better understand the performance of this treatment and the role of NfL in Alzheimer’s disease,” Dr. Weber said.

Also providing outside perspective, Howard Fillit, MD, founding executive director of the Alzheimer’s Drug Discovery Foundation, noted that currently “there is a lot of effort in trying to address the abnormal tau that occurs in Alzheimer’s disease.”

The biomarker data from LUCIDITY show that HMTM “seems to markedly decrease the amount of NfL in plasma and there is some correlation with cognitive scores. The obvious unknown is whether these changes in plasma NfL will predict clinical benefit,” Dr. Fillit said in an interview.

“This is an oral drug that has a good safety profile, and the mechanism of action makes sense, but we need to see the clinical data,” Dr. Fillit said.

Final 2-year data from the LUCIDITY trial are expected to be released later in 2023.

In the United Kingdom, TauRx has entered an accelerated approval process for the drug, and the company said it plans to seek regulatory approval in the United States and Canada in 2023.

The study was funded by TauRx Therapeutics. Dr. Wischik is an employee of the University of Aberdeen (Scotland), and TauRx Therapeutics. Dr. Weber and Dr. Fillit reported no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The effect of the highly touted MIND diet with mild calorie restriction offered no greater protection against cognitive decline than a control diet with mild calorie restriction alone in healthy adults at risk for dementia, results of a new randomized trial show.

Given the strong base of evidence from observational studies that demonstrate the benefits of the MIND diet on cognitive decline, Alzheimer’s disease (AD), and neuropathologic changes such as reduced beta amyloid and tau associated with AD, the study’s results were “unexpected,” study investigator Lisa L. Barnes, PhD, with the Rush Alzheimer’s Disease Center, Chicago, said in an interview.

“One possibility is the trial may not have been long enough to see an effect. It’s also possible that participants in the control diet group benefited just as much as those in the MIND diet group because they also improved their diets to focus on weight loss,” Dr. Barnes said.

“Although we did not see a specific effect of the MIND diet, people in both groups improved their cognitive function, suggesting that a healthy diet in general is good for cognitive function,” she added.

The findings were presented at the annual Alzheimer’s Association International Conference and simultaneously published online in the New England Journal of Medicine.
 

Randomized trial

A hybrid of the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet, the MIND diet includes foods and nutrients that have been putatively associated with a decreased risk of dementia.

To further investigate, the researchers conducted a randomized trial that included 604 older adults without cognitive impairment who had a family history of dementia, a body mass index greater than 25, and a suboptimal diet determined via a 14-item questionnaire.

For 3 years, 301 were randomly assigned to follow the MIND-diet with mild calorie restriction and 303 to follow a control diet with mild calorie restriction only. All participants received counseling to help them adhere to their assigned diet, plus support to promote weight loss of 3%-5% by year 3.

The primary endpoint was the change from baseline in global cognition and in specific cognitive domains through year 3. Cognition was assessed with an established battery of 12 publicly available cognitive function tests.

The secondary endpoint was the change from baseline in MRI-derived measures of brain characteristics in a nonrandom sample of participants.

“We had good adherence to the assigned diets and both groups lost weight, on average about 5 kilograms in both groups,” Dr. Barnes noted in her presentation.

From baseline through 3 years, small improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group versus 0.170 standardized units in the control-diet group.

However, in intention-to-treat analysis, the mean change in score did not differ significantly between groups, with an estimated mean difference at the end of the trial of 0.035 standardized units (P = .23).

At the trial’s conclusion, there were also no between-group differences in change in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI.

Dr. Barnes noted that the trial was limited to well-educated, older adults, mostly of European descent. Other limitations include the small sample size of those who received MRI and follow-up that was shorter than a typical observational study.

Dr. Barnes noted that this is a single study and that there needs to be more randomized trials of the MIND diet that, as with the observational research, follow participants for a longer period of time.
 

More to brain health than diet

Reached for comment, Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at George Washington University, Washington, noted that participants who enroll in clinical trials that focus on diet become more aware of their eating habits and shift toward a healthier diet.

“This may explain the reason why both groups of participants in this study improved,” said Dr. Fotuhi, medical director of NeuroGrow Brain Fitness Center, McLean, Va.

However, he believes that better brain health requires a multipronged approach.

“In order to see significant results, people need to improve their diet, become physically fit, sleep well, reduce their stress, engage in cognitively challenging activities, and develop a positive mind set,” said Dr. Fotuhi.

“Interventions that target only one of these goals may not produce results that are as remarkable as multimodal programs, which target all of these goals,” Dr. Fotuhi said.

Dr. Fotuhi developed a multidimensional “brain fitness program” that has shown to provide multiple benefits for individuals with memory loss, attention deficit hyperactivity disorder, and post-concussion syndrome.

“Having provided our 12-week program for thousands of patients in the past 10 years, I have noticed a synergistic effect in patients who incorporate all of these changes in their day-to-day life and maintain it over time. They often become sharper and feel better overall,” Dr. Fotuhi told this news organization.

The study was supported by the National Institute on Aging. Disclosures for study authors are listed with the original article. Dr. Fotuhi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The effect of the highly touted MIND diet with mild calorie restriction offered no greater protection against cognitive decline than a control diet with mild calorie restriction alone in healthy adults at risk for dementia, results of a new randomized trial show.

Given the strong base of evidence from observational studies that demonstrate the benefits of the MIND diet on cognitive decline, Alzheimer’s disease (AD), and neuropathologic changes such as reduced beta amyloid and tau associated with AD, the study’s results were “unexpected,” study investigator Lisa L. Barnes, PhD, with the Rush Alzheimer’s Disease Center, Chicago, said in an interview.

“One possibility is the trial may not have been long enough to see an effect. It’s also possible that participants in the control diet group benefited just as much as those in the MIND diet group because they also improved their diets to focus on weight loss,” Dr. Barnes said.

“Although we did not see a specific effect of the MIND diet, people in both groups improved their cognitive function, suggesting that a healthy diet in general is good for cognitive function,” she added.

The findings were presented at the annual Alzheimer’s Association International Conference and simultaneously published online in the New England Journal of Medicine.
 

Randomized trial

A hybrid of the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet, the MIND diet includes foods and nutrients that have been putatively associated with a decreased risk of dementia.

To further investigate, the researchers conducted a randomized trial that included 604 older adults without cognitive impairment who had a family history of dementia, a body mass index greater than 25, and a suboptimal diet determined via a 14-item questionnaire.

For 3 years, 301 were randomly assigned to follow the MIND-diet with mild calorie restriction and 303 to follow a control diet with mild calorie restriction only. All participants received counseling to help them adhere to their assigned diet, plus support to promote weight loss of 3%-5% by year 3.

The primary endpoint was the change from baseline in global cognition and in specific cognitive domains through year 3. Cognition was assessed with an established battery of 12 publicly available cognitive function tests.

The secondary endpoint was the change from baseline in MRI-derived measures of brain characteristics in a nonrandom sample of participants.

“We had good adherence to the assigned diets and both groups lost weight, on average about 5 kilograms in both groups,” Dr. Barnes noted in her presentation.

From baseline through 3 years, small improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group versus 0.170 standardized units in the control-diet group.

However, in intention-to-treat analysis, the mean change in score did not differ significantly between groups, with an estimated mean difference at the end of the trial of 0.035 standardized units (P = .23).

At the trial’s conclusion, there were also no between-group differences in change in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI.

Dr. Barnes noted that the trial was limited to well-educated, older adults, mostly of European descent. Other limitations include the small sample size of those who received MRI and follow-up that was shorter than a typical observational study.

Dr. Barnes noted that this is a single study and that there needs to be more randomized trials of the MIND diet that, as with the observational research, follow participants for a longer period of time.
 

More to brain health than diet

Reached for comment, Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at George Washington University, Washington, noted that participants who enroll in clinical trials that focus on diet become more aware of their eating habits and shift toward a healthier diet.

“This may explain the reason why both groups of participants in this study improved,” said Dr. Fotuhi, medical director of NeuroGrow Brain Fitness Center, McLean, Va.

However, he believes that better brain health requires a multipronged approach.

“In order to see significant results, people need to improve their diet, become physically fit, sleep well, reduce their stress, engage in cognitively challenging activities, and develop a positive mind set,” said Dr. Fotuhi.

“Interventions that target only one of these goals may not produce results that are as remarkable as multimodal programs, which target all of these goals,” Dr. Fotuhi said.

Dr. Fotuhi developed a multidimensional “brain fitness program” that has shown to provide multiple benefits for individuals with memory loss, attention deficit hyperactivity disorder, and post-concussion syndrome.

“Having provided our 12-week program for thousands of patients in the past 10 years, I have noticed a synergistic effect in patients who incorporate all of these changes in their day-to-day life and maintain it over time. They often become sharper and feel better overall,” Dr. Fotuhi told this news organization.

The study was supported by the National Institute on Aging. Disclosures for study authors are listed with the original article. Dr. Fotuhi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

The effect of the highly touted MIND diet with mild calorie restriction offered no greater protection against cognitive decline than a control diet with mild calorie restriction alone in healthy adults at risk for dementia, results of a new randomized trial show.

Given the strong base of evidence from observational studies that demonstrate the benefits of the MIND diet on cognitive decline, Alzheimer’s disease (AD), and neuropathologic changes such as reduced beta amyloid and tau associated with AD, the study’s results were “unexpected,” study investigator Lisa L. Barnes, PhD, with the Rush Alzheimer’s Disease Center, Chicago, said in an interview.

“One possibility is the trial may not have been long enough to see an effect. It’s also possible that participants in the control diet group benefited just as much as those in the MIND diet group because they also improved their diets to focus on weight loss,” Dr. Barnes said.

“Although we did not see a specific effect of the MIND diet, people in both groups improved their cognitive function, suggesting that a healthy diet in general is good for cognitive function,” she added.

The findings were presented at the annual Alzheimer’s Association International Conference and simultaneously published online in the New England Journal of Medicine.
 

Randomized trial

A hybrid of the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diet, the MIND diet includes foods and nutrients that have been putatively associated with a decreased risk of dementia.

To further investigate, the researchers conducted a randomized trial that included 604 older adults without cognitive impairment who had a family history of dementia, a body mass index greater than 25, and a suboptimal diet determined via a 14-item questionnaire.

For 3 years, 301 were randomly assigned to follow the MIND-diet with mild calorie restriction and 303 to follow a control diet with mild calorie restriction only. All participants received counseling to help them adhere to their assigned diet, plus support to promote weight loss of 3%-5% by year 3.

The primary endpoint was the change from baseline in global cognition and in specific cognitive domains through year 3. Cognition was assessed with an established battery of 12 publicly available cognitive function tests.

The secondary endpoint was the change from baseline in MRI-derived measures of brain characteristics in a nonrandom sample of participants.

“We had good adherence to the assigned diets and both groups lost weight, on average about 5 kilograms in both groups,” Dr. Barnes noted in her presentation.

From baseline through 3 years, small improvements in global cognition scores were observed in both groups, with increases of 0.205 standardized units in the MIND-diet group versus 0.170 standardized units in the control-diet group.

However, in intention-to-treat analysis, the mean change in score did not differ significantly between groups, with an estimated mean difference at the end of the trial of 0.035 standardized units (P = .23).

At the trial’s conclusion, there were also no between-group differences in change in white-matter hyperintensities, hippocampal volumes, and total gray- and white-matter volumes on MRI.

Dr. Barnes noted that the trial was limited to well-educated, older adults, mostly of European descent. Other limitations include the small sample size of those who received MRI and follow-up that was shorter than a typical observational study.

Dr. Barnes noted that this is a single study and that there needs to be more randomized trials of the MIND diet that, as with the observational research, follow participants for a longer period of time.
 

More to brain health than diet

Reached for comment, Majid Fotuhi, MD, PhD, adjunct professor of neuroscience at George Washington University, Washington, noted that participants who enroll in clinical trials that focus on diet become more aware of their eating habits and shift toward a healthier diet.

“This may explain the reason why both groups of participants in this study improved,” said Dr. Fotuhi, medical director of NeuroGrow Brain Fitness Center, McLean, Va.

However, he believes that better brain health requires a multipronged approach.

“In order to see significant results, people need to improve their diet, become physically fit, sleep well, reduce their stress, engage in cognitively challenging activities, and develop a positive mind set,” said Dr. Fotuhi.

“Interventions that target only one of these goals may not produce results that are as remarkable as multimodal programs, which target all of these goals,” Dr. Fotuhi said.

Dr. Fotuhi developed a multidimensional “brain fitness program” that has shown to provide multiple benefits for individuals with memory loss, attention deficit hyperactivity disorder, and post-concussion syndrome.

“Having provided our 12-week program for thousands of patients in the past 10 years, I have noticed a synergistic effect in patients who incorporate all of these changes in their day-to-day life and maintain it over time. They often become sharper and feel better overall,” Dr. Fotuhi told this news organization.

The study was supported by the National Institute on Aging. Disclosures for study authors are listed with the original article. Dr. Fotuhi has disclosed no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Physicians’ demonstrations of empathy toward their patients can decrease the sensation of pain. These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.

The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.

Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
 

Worse when alone

Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.

The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
 

Evidence of trust

There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.

“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
 

Beyond medication

Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”

“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.

“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
 

Perception and attitude

“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.

“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
 

Positive expectations

Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.

Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

Physicians’ demonstrations of empathy toward their patients can decrease the sensation of pain. These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.

The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.

Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
 

Worse when alone

Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.

The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
 

Evidence of trust

There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.

“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
 

Beyond medication

Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”

“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.

“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
 

Perception and attitude

“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.

“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
 

Positive expectations

Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.

Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.

Physicians’ demonstrations of empathy toward their patients can decrease the sensation of pain. These are the results of a study, recently published in the Proceedings of the National Academy of Sciences, that was conducted by a team led by neuroscientist Dan-Mikael Ellingsen, PhD, from Oslo University Hospital.

The researchers used functional MRI to scan the brains of 20 patients with chronic pain to investigate how a physician’s demeanor may affect patients’ sensitivity to pain, including effects in the central nervous system. During the scans, which were conducted in two sessions, the patients’ legs were exposed to stimuli that ranged from painless to moderately painful. The patients recorded perceived pain intensity using a scale. The physicians also underwent fMRI.

Half of the patients were subjected to the pain stimuli while alone; the other half were subjected to pain while in the presence of a physician. The latter group of patients was divided into two subgroups. Half of the patients had spoken to the accompanying physician before the examination. They discussed the history of the patient’s condition to date, among other things. The other half underwent the brain scans without any prior interaction with a physician.
 

Worse when alone

Dr. Ellingsen and his colleagues found that patients who were alone during the examination reported greater pain than those who were in the presence of a physician, even though they were subjected to stimuli of the same intensity. In instances in which the physician and patient had already spoken before the brain scan, patients additionally felt that the physician was empathetic and understood their pain. Furthermore, the physicians were better able to estimate the pain that their patients experienced.

The patients who had a physician by their side consistently experienced pain that was milder than the pain experienced by those who were alone. For pairs that had spoken beforehand, the patients considered their physician to be better able to understand their pain, and the physicians estimated the perceived pain intensity of their patients more accurately.
 

Evidence of trust

There was greater activity in the dorsolateral and ventrolateral prefrontal cortex, as well as in the primary and secondary somatosensory areas, in patients in the subgroup that had spoken to a physician. For the physicians, compared with the comparison group, there was an increase in correspondence between activity in the dorsolateral prefrontal cortex and activity in the secondary somatosensory areas of patients, which is a brain region that is known to react to pain. The brain activity correlation increased in line with the self-reported mutual trust between the physician and patient.

“These results prove that empathy and support can decrease pain intensity,” the investigators write. The data shed light on the brain processes behind the social modulation of pain during the interaction between the physician and the patient. Concordances in the brain are increased by greater therapeutic alliance.
 

Beyond medication

Winfried Meissner, MD, head of the pain clinic at the department of anesthesiology and intensive care medicine at Jena University Hospital, Germany, and former president of the German Pain Society, said in an interview: “I view this as a vital study that impressively demonstrates that effective, intensive pain therapy is not just a case of administering the correct analgesic.”

“Instead, a focus should be placed on what common sense tells us, which is just how crucial an empathetic attitude from physicians and good communication with patients are when it comes to the success of any therapy,” Dr. Meissner added. Unfortunately, such an attitude and such communication often are not provided in clinical practice because of limitations on time.

“Now, with objectively collected data from patients and physicians, [Dr.] Ellingsen’s team has been able to demonstrate that human interaction has a decisive impact on the treatment of patients experiencing pain,” said Dr. Meissner. “The study should encourage practitioners to treat communication just as seriously as the pharmacology of analgesics.”
 

Perception and attitude

“The study shows remarkably well that empathetic conversation between the physician and patient represents a valuable therapeutic method and should be recognized as such,” emphasized Dr. Meissner. Of course, conversation cannot replace pharmacologic treatment, but it can supplement and reinforce it. Furthermore, a physician’s empathy presumably has an effect that is at least as great as a suitable analgesic.

“Pain is more than just sensory perception,” explained Dr. Meissner. “We all know that it has a strong affective component, and perception is greatly determined by context.” This can be seen, for example, in athletes, who often attribute less importance to their pain and can successfully perform competitively despite a painful injury.
 

Positive expectations

Dr. Meissner advised all physicians to treat patients with pain empathetically. He encourages them to ask patients about their pain, accompanying symptoms, possible fears, and other mental stress and to take these factors seriously.

Moreover, the findings accentuate the effect of prescribed analgesics. “Numerous studies have meanwhile shown that the more positive a patient’s expectations, the better the effect of a medication,” said Dr. Meissner. “We physicians must exploit this effect, too.”

This article was translated from the Medscape German Edition and a version appeared on Medscape.com.