Neurology

This transcript has been edited for clarity.

Kathrin LaFaver, MD: Hello. I’m happy to talk today to Dr. Indu Subramanian, clinical professor at University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education and Clinical Center in Los Angeles. I am a neurologist in Saratoga Springs, New York, and we will be talking today about Indu’s new paper on childhood trauma and Parkinson’s disease. Welcome and thanks for taking the time.

Indu Subramanian, MD: Thank you so much for letting us highlight this important topic.

Dr. LaFaver: There are many papers published every month on Parkinson’s disease, but this topic stands out because it’s not a thing that has been commonly looked at. What gave you the idea to study this?
 

Neurology behind other specialties

Dr. Subramanian: Kathrin, you and I have been looking at things that can inform us about our patients – the person who’s standing in front of us when they come in and we’re giving them this diagnosis. I think that so much of what we’ve done [in the past] is a cookie cutter approach to giving everybody the standard treatment. [We’ve been assuming that] It doesn’t matter if they’re a man or woman. It doesn’t matter if they’re a veteran. It doesn’t matter if they may be from a minoritized population.

Customization is so key, and we’re realizing that we have missed the boat often through the pandemic and in health care in general.

We’ve also been interested in approaches that are outside the box, right? We have this integrative medicine and lifestyle medicine background. I’ve been going to those meetings and really been struck by the mounting evidence on the importance of things like early adverse childhood events (ACEs), what zip code you live in, what your pollution index is, and how these things can affect people through their life and their health.

I think that it is high time neurologists pay attention to this. There’s been mounting evidence throughout many disease states, various types of cancers, and mental health. Cardiology is much more advanced, but we haven’t had much data in neurology. In fact, when we went to write this paper, there were just one or two papers that were looking at multiple sclerosis or general neurologic issues, but really nothing in Parkinson’s disease.

We know that Parkinson’s disease is not only a motor disease that affects mental health, but that it also affects nonmotor issues. Childhood adversity may affect how people progress or how quickly they may get a disease, and we were interested in how it may manifest in a disease like Parkinson’s disease.

That was the framework going to meetings. As we wrote this paper and were in various editing stages, there was a beautiful paper that came out by Nadine Burke Harris and team that really was a call to action for neurologists and caring about trauma.

Dr. LaFaver: I couldn’t agree more. It’s really an underrecognized issue. With my own background, being very interested in functional movement disorders, psychosomatic disorders, and so on, it becomes much more evident how common a trauma background is, not only for people we were traditionally asking about.

Why don’t you summarize your findings for us?
 

Adverse childhood events

Dr. Subramanian: This is a web-based survey, so obviously, these are patient self-reports of their disease. We have a large cohort of people that we’ve been following over 7 years. I’m looking at modifiable variables and what really impacts Parkinson’s disease. Some of our previous papers have looked at diet, exercise, and loneliness. This is the same cohort.

We ended up putting the ACEs questionnaire, which is 10 questions looking at whether you were exposed to certain things in your household below the age of 18. This is a relatively standard questionnaire that’s administered one time, and you get a score out of 10. This is something that has been pushed, at least in the state of California, as something that we should be checking more in all people coming in.

We introduced the survey, and we didn’t force everyone to take it. Unfortunately, there was 20% or so of our patients who chose not to answer these questions. One has to ask, who are those people that didn’t answer the questions? Are they the ones that may have had trauma and these questions were triggering? It was a gap. We didn’t add extra questions to explore why people didn’t answer those questions.

We have to also put this in context. We have a patient population that’s largely quite affluent, who are able to access web-based surveys through their computer, and largely Caucasian; there are not many minoritized populations in our cohort. We want to do better with that. We actually were able to gather a decent number of women. We represent women quite well in our survey. I think that’s because of this online approach and some of the things that we’re studying.

In our survey, we broke it down into people who had no ACEs, one to three ACEs, or four or more ACEs. This is a standard way to break down ACEs so that we’re able to categorize what to do with these patient populations.

What we saw – and it’s preliminary evidence – is that people who had higher ACE scores seemed to have more symptom severity when we controlled for things like years since diagnosis, age, and gender. They also seem to have a worse quality of life. There was some indication that there were more nonmotor issues in those populations, as you might expect, such as anxiety, depression, and things that presumably ACEs can affect separately.

There are some confounders, but I think we really want to use this as the first piece of evidence to hopefully pave the way for caring about trauma in Parkinson’s disease moving forward.

Dr. LaFaver: Thank you so much for that summary. You already mentioned the main methodology you used.

What is the next step for you? How do you see these findings informing our clinical care? Do you have suggestions for all of the neurologists listening in this regard?


 

PD not yet considered ACE-related

Dr. Subramanian: Dr. Burke Harris was the former surgeon general in California. She’s a woman of color and a brilliant speaker, and she had worked in inner cities, I think in San Francisco, with pediatric populations, seeing these effects of adversity in that time frame.

You see this population at risk, and then you’re following this cohort, which we knew from the Kaiser cohort determines earlier morbidity and mortality across a number of disease states. We’re seeing things like more heart attacks, more diabetes, and all kinds of things in these populations. This is not new news; we just have not been focusing on this.

In her paper, this call to action, they had talked about some ACE-related conditions that currently do not include Parkinson’s disease. There are three ACE-related neurologic conditions that people should be aware of. One is in the headache/pain universe. Another is in the stroke universe, and that’s understandable, given cardiovascular risk factors . Then the third is in this dementia risk category. I think Parkinson’s disease, as we know, can be associated with dementia. A large percentage of our patients get dementia, but we don’t have Parkinson’s disease called out in this framework.

What people are talking about is if you have no ACEs or are in this middle category of one to three ACEs and you don’t have an ACE-related diagnosis – which Parkinson’s disease is not currently – we just give some basic counseling about the importance of lifestyle. I think we would love to see that anyway. They’re talking about things like exercise, diet, sleep, social connection, getting out in nature, things like that, so just general counseling on the importance of that.

Then if you’re in this higher-risk category, and so with these ACE-related neurologic conditions, including dementia, headache, and stroke, if you had this middle range of one to three ACEs, they’re getting additional resources. Some of them may be referred for social work help or mental health support and things like that.

I’d really love to see that happening in Parkinson’s disease, because I think we have so many needs in our population. I’m always hoping to advocate for more mental health needs that are scarce and resources in the social support realm because I believe that social connection and social support is a huge buffer for this trauma.

ACEs are just one type of trauma. I take care of veterans in the Veterans [Affairs Department]. We have some information now coming out about posttraumatic stress disorder, predisposing to certain things in Parkinson’s disease, possibly head injury, and things like that. I think we have populations at risk that we can hopefully screen at intake, and I’m really pushing for that.

Maybe it’s not the neurologist that does this intake. It might be someone else on the team that can spend some time doing these questionnaires and understand if your patient has a high ACE score. Unless you ask, many patients don’t necessarily come forward to talk about this. I really am pushing for trying to screen and trying to advocate for more research in this area so that we can classify Parkinson’s disease as an ACE-related condition and thus give more resources from the mental health world, and also the social support world, to our patients.

Dr. LaFaver: Thank you. There are many important points, and I think it’s a very important thing to recognize that it may not be only trauma in childhood but also throughout life, as you said, and might really influence nonmotor symptoms of Parkinson’s disease in particular, including anxiety and pain, which are often difficult to treat.

I think there’s much more to do in research, advocacy, and education. We’re going to educate patients about this, and also educate other neurologists and providers. I think you mentioned that trauma-informed care is getting its spotlight in primary care and other specialties. I think we have catching up to do in neurology, and I think this is a really important work toward that goal.

Thank you so much for your work and for taking the time to share your thoughts. I hope to talk to you again soon.

Dr. Subramanian: Thank you so much, Kathrin.
 

Dr. LaFaver has disclosed no relevant financial relationships. Dr. Subramanian disclosed ties with Acorda Therapeutics.

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

This transcript has been edited for clarity.

Kathrin LaFaver, MD: Hello. I’m happy to talk today to Dr. Indu Subramanian, clinical professor at University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education and Clinical Center in Los Angeles. I am a neurologist in Saratoga Springs, New York, and we will be talking today about Indu’s new paper on childhood trauma and Parkinson’s disease. Welcome and thanks for taking the time.

Indu Subramanian, MD: Thank you so much for letting us highlight this important topic.

Dr. LaFaver: There are many papers published every month on Parkinson’s disease, but this topic stands out because it’s not a thing that has been commonly looked at. What gave you the idea to study this?
 

Neurology behind other specialties

Dr. Subramanian: Kathrin, you and I have been looking at things that can inform us about our patients – the person who’s standing in front of us when they come in and we’re giving them this diagnosis. I think that so much of what we’ve done [in the past] is a cookie cutter approach to giving everybody the standard treatment. [We’ve been assuming that] It doesn’t matter if they’re a man or woman. It doesn’t matter if they’re a veteran. It doesn’t matter if they may be from a minoritized population.

Customization is so key, and we’re realizing that we have missed the boat often through the pandemic and in health care in general.

We’ve also been interested in approaches that are outside the box, right? We have this integrative medicine and lifestyle medicine background. I’ve been going to those meetings and really been struck by the mounting evidence on the importance of things like early adverse childhood events (ACEs), what zip code you live in, what your pollution index is, and how these things can affect people through their life and their health.

I think that it is high time neurologists pay attention to this. There’s been mounting evidence throughout many disease states, various types of cancers, and mental health. Cardiology is much more advanced, but we haven’t had much data in neurology. In fact, when we went to write this paper, there were just one or two papers that were looking at multiple sclerosis or general neurologic issues, but really nothing in Parkinson’s disease.

We know that Parkinson’s disease is not only a motor disease that affects mental health, but that it also affects nonmotor issues. Childhood adversity may affect how people progress or how quickly they may get a disease, and we were interested in how it may manifest in a disease like Parkinson’s disease.

That was the framework going to meetings. As we wrote this paper and were in various editing stages, there was a beautiful paper that came out by Nadine Burke Harris and team that really was a call to action for neurologists and caring about trauma.

Dr. LaFaver: I couldn’t agree more. It’s really an underrecognized issue. With my own background, being very interested in functional movement disorders, psychosomatic disorders, and so on, it becomes much more evident how common a trauma background is, not only for people we were traditionally asking about.

Why don’t you summarize your findings for us?
 

Adverse childhood events

Dr. Subramanian: This is a web-based survey, so obviously, these are patient self-reports of their disease. We have a large cohort of people that we’ve been following over 7 years. I’m looking at modifiable variables and what really impacts Parkinson’s disease. Some of our previous papers have looked at diet, exercise, and loneliness. This is the same cohort.

We ended up putting the ACEs questionnaire, which is 10 questions looking at whether you were exposed to certain things in your household below the age of 18. This is a relatively standard questionnaire that’s administered one time, and you get a score out of 10. This is something that has been pushed, at least in the state of California, as something that we should be checking more in all people coming in.

We introduced the survey, and we didn’t force everyone to take it. Unfortunately, there was 20% or so of our patients who chose not to answer these questions. One has to ask, who are those people that didn’t answer the questions? Are they the ones that may have had trauma and these questions were triggering? It was a gap. We didn’t add extra questions to explore why people didn’t answer those questions.

We have to also put this in context. We have a patient population that’s largely quite affluent, who are able to access web-based surveys through their computer, and largely Caucasian; there are not many minoritized populations in our cohort. We want to do better with that. We actually were able to gather a decent number of women. We represent women quite well in our survey. I think that’s because of this online approach and some of the things that we’re studying.

In our survey, we broke it down into people who had no ACEs, one to three ACEs, or four or more ACEs. This is a standard way to break down ACEs so that we’re able to categorize what to do with these patient populations.

What we saw – and it’s preliminary evidence – is that people who had higher ACE scores seemed to have more symptom severity when we controlled for things like years since diagnosis, age, and gender. They also seem to have a worse quality of life. There was some indication that there were more nonmotor issues in those populations, as you might expect, such as anxiety, depression, and things that presumably ACEs can affect separately.

There are some confounders, but I think we really want to use this as the first piece of evidence to hopefully pave the way for caring about trauma in Parkinson’s disease moving forward.

Dr. LaFaver: Thank you so much for that summary. You already mentioned the main methodology you used.

What is the next step for you? How do you see these findings informing our clinical care? Do you have suggestions for all of the neurologists listening in this regard?


 

PD not yet considered ACE-related

Dr. Subramanian: Dr. Burke Harris was the former surgeon general in California. She’s a woman of color and a brilliant speaker, and she had worked in inner cities, I think in San Francisco, with pediatric populations, seeing these effects of adversity in that time frame.

You see this population at risk, and then you’re following this cohort, which we knew from the Kaiser cohort determines earlier morbidity and mortality across a number of disease states. We’re seeing things like more heart attacks, more diabetes, and all kinds of things in these populations. This is not new news; we just have not been focusing on this.

In her paper, this call to action, they had talked about some ACE-related conditions that currently do not include Parkinson’s disease. There are three ACE-related neurologic conditions that people should be aware of. One is in the headache/pain universe. Another is in the stroke universe, and that’s understandable, given cardiovascular risk factors . Then the third is in this dementia risk category. I think Parkinson’s disease, as we know, can be associated with dementia. A large percentage of our patients get dementia, but we don’t have Parkinson’s disease called out in this framework.

What people are talking about is if you have no ACEs or are in this middle category of one to three ACEs and you don’t have an ACE-related diagnosis – which Parkinson’s disease is not currently – we just give some basic counseling about the importance of lifestyle. I think we would love to see that anyway. They’re talking about things like exercise, diet, sleep, social connection, getting out in nature, things like that, so just general counseling on the importance of that.

Then if you’re in this higher-risk category, and so with these ACE-related neurologic conditions, including dementia, headache, and stroke, if you had this middle range of one to three ACEs, they’re getting additional resources. Some of them may be referred for social work help or mental health support and things like that.

I’d really love to see that happening in Parkinson’s disease, because I think we have so many needs in our population. I’m always hoping to advocate for more mental health needs that are scarce and resources in the social support realm because I believe that social connection and social support is a huge buffer for this trauma.

ACEs are just one type of trauma. I take care of veterans in the Veterans [Affairs Department]. We have some information now coming out about posttraumatic stress disorder, predisposing to certain things in Parkinson’s disease, possibly head injury, and things like that. I think we have populations at risk that we can hopefully screen at intake, and I’m really pushing for that.

Maybe it’s not the neurologist that does this intake. It might be someone else on the team that can spend some time doing these questionnaires and understand if your patient has a high ACE score. Unless you ask, many patients don’t necessarily come forward to talk about this. I really am pushing for trying to screen and trying to advocate for more research in this area so that we can classify Parkinson’s disease as an ACE-related condition and thus give more resources from the mental health world, and also the social support world, to our patients.

Dr. LaFaver: Thank you. There are many important points, and I think it’s a very important thing to recognize that it may not be only trauma in childhood but also throughout life, as you said, and might really influence nonmotor symptoms of Parkinson’s disease in particular, including anxiety and pain, which are often difficult to treat.

I think there’s much more to do in research, advocacy, and education. We’re going to educate patients about this, and also educate other neurologists and providers. I think you mentioned that trauma-informed care is getting its spotlight in primary care and other specialties. I think we have catching up to do in neurology, and I think this is a really important work toward that goal.

Thank you so much for your work and for taking the time to share your thoughts. I hope to talk to you again soon.

Dr. Subramanian: Thank you so much, Kathrin.
 

Dr. LaFaver has disclosed no relevant financial relationships. Dr. Subramanian disclosed ties with Acorda Therapeutics.

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

This transcript has been edited for clarity.

Kathrin LaFaver, MD: Hello. I’m happy to talk today to Dr. Indu Subramanian, clinical professor at University of California, Los Angeles, and director of the Parkinson’s Disease Research, Education and Clinical Center in Los Angeles. I am a neurologist in Saratoga Springs, New York, and we will be talking today about Indu’s new paper on childhood trauma and Parkinson’s disease. Welcome and thanks for taking the time.

Indu Subramanian, MD: Thank you so much for letting us highlight this important topic.

Dr. LaFaver: There are many papers published every month on Parkinson’s disease, but this topic stands out because it’s not a thing that has been commonly looked at. What gave you the idea to study this?
 

Neurology behind other specialties

Dr. Subramanian: Kathrin, you and I have been looking at things that can inform us about our patients – the person who’s standing in front of us when they come in and we’re giving them this diagnosis. I think that so much of what we’ve done [in the past] is a cookie cutter approach to giving everybody the standard treatment. [We’ve been assuming that] It doesn’t matter if they’re a man or woman. It doesn’t matter if they’re a veteran. It doesn’t matter if they may be from a minoritized population.

Customization is so key, and we’re realizing that we have missed the boat often through the pandemic and in health care in general.

We’ve also been interested in approaches that are outside the box, right? We have this integrative medicine and lifestyle medicine background. I’ve been going to those meetings and really been struck by the mounting evidence on the importance of things like early adverse childhood events (ACEs), what zip code you live in, what your pollution index is, and how these things can affect people through their life and their health.

I think that it is high time neurologists pay attention to this. There’s been mounting evidence throughout many disease states, various types of cancers, and mental health. Cardiology is much more advanced, but we haven’t had much data in neurology. In fact, when we went to write this paper, there were just one or two papers that were looking at multiple sclerosis or general neurologic issues, but really nothing in Parkinson’s disease.

We know that Parkinson’s disease is not only a motor disease that affects mental health, but that it also affects nonmotor issues. Childhood adversity may affect how people progress or how quickly they may get a disease, and we were interested in how it may manifest in a disease like Parkinson’s disease.

That was the framework going to meetings. As we wrote this paper and were in various editing stages, there was a beautiful paper that came out by Nadine Burke Harris and team that really was a call to action for neurologists and caring about trauma.

Dr. LaFaver: I couldn’t agree more. It’s really an underrecognized issue. With my own background, being very interested in functional movement disorders, psychosomatic disorders, and so on, it becomes much more evident how common a trauma background is, not only for people we were traditionally asking about.

Why don’t you summarize your findings for us?
 

Adverse childhood events

Dr. Subramanian: This is a web-based survey, so obviously, these are patient self-reports of their disease. We have a large cohort of people that we’ve been following over 7 years. I’m looking at modifiable variables and what really impacts Parkinson’s disease. Some of our previous papers have looked at diet, exercise, and loneliness. This is the same cohort.

We ended up putting the ACEs questionnaire, which is 10 questions looking at whether you were exposed to certain things in your household below the age of 18. This is a relatively standard questionnaire that’s administered one time, and you get a score out of 10. This is something that has been pushed, at least in the state of California, as something that we should be checking more in all people coming in.

We introduced the survey, and we didn’t force everyone to take it. Unfortunately, there was 20% or so of our patients who chose not to answer these questions. One has to ask, who are those people that didn’t answer the questions? Are they the ones that may have had trauma and these questions were triggering? It was a gap. We didn’t add extra questions to explore why people didn’t answer those questions.

We have to also put this in context. We have a patient population that’s largely quite affluent, who are able to access web-based surveys through their computer, and largely Caucasian; there are not many minoritized populations in our cohort. We want to do better with that. We actually were able to gather a decent number of women. We represent women quite well in our survey. I think that’s because of this online approach and some of the things that we’re studying.

In our survey, we broke it down into people who had no ACEs, one to three ACEs, or four or more ACEs. This is a standard way to break down ACEs so that we’re able to categorize what to do with these patient populations.

What we saw – and it’s preliminary evidence – is that people who had higher ACE scores seemed to have more symptom severity when we controlled for things like years since diagnosis, age, and gender. They also seem to have a worse quality of life. There was some indication that there were more nonmotor issues in those populations, as you might expect, such as anxiety, depression, and things that presumably ACEs can affect separately.

There are some confounders, but I think we really want to use this as the first piece of evidence to hopefully pave the way for caring about trauma in Parkinson’s disease moving forward.

Dr. LaFaver: Thank you so much for that summary. You already mentioned the main methodology you used.

What is the next step for you? How do you see these findings informing our clinical care? Do you have suggestions for all of the neurologists listening in this regard?


 

PD not yet considered ACE-related

Dr. Subramanian: Dr. Burke Harris was the former surgeon general in California. She’s a woman of color and a brilliant speaker, and she had worked in inner cities, I think in San Francisco, with pediatric populations, seeing these effects of adversity in that time frame.

You see this population at risk, and then you’re following this cohort, which we knew from the Kaiser cohort determines earlier morbidity and mortality across a number of disease states. We’re seeing things like more heart attacks, more diabetes, and all kinds of things in these populations. This is not new news; we just have not been focusing on this.

In her paper, this call to action, they had talked about some ACE-related conditions that currently do not include Parkinson’s disease. There are three ACE-related neurologic conditions that people should be aware of. One is in the headache/pain universe. Another is in the stroke universe, and that’s understandable, given cardiovascular risk factors . Then the third is in this dementia risk category. I think Parkinson’s disease, as we know, can be associated with dementia. A large percentage of our patients get dementia, but we don’t have Parkinson’s disease called out in this framework.

What people are talking about is if you have no ACEs or are in this middle category of one to three ACEs and you don’t have an ACE-related diagnosis – which Parkinson’s disease is not currently – we just give some basic counseling about the importance of lifestyle. I think we would love to see that anyway. They’re talking about things like exercise, diet, sleep, social connection, getting out in nature, things like that, so just general counseling on the importance of that.

Then if you’re in this higher-risk category, and so with these ACE-related neurologic conditions, including dementia, headache, and stroke, if you had this middle range of one to three ACEs, they’re getting additional resources. Some of them may be referred for social work help or mental health support and things like that.

I’d really love to see that happening in Parkinson’s disease, because I think we have so many needs in our population. I’m always hoping to advocate for more mental health needs that are scarce and resources in the social support realm because I believe that social connection and social support is a huge buffer for this trauma.

ACEs are just one type of trauma. I take care of veterans in the Veterans [Affairs Department]. We have some information now coming out about posttraumatic stress disorder, predisposing to certain things in Parkinson’s disease, possibly head injury, and things like that. I think we have populations at risk that we can hopefully screen at intake, and I’m really pushing for that.

Maybe it’s not the neurologist that does this intake. It might be someone else on the team that can spend some time doing these questionnaires and understand if your patient has a high ACE score. Unless you ask, many patients don’t necessarily come forward to talk about this. I really am pushing for trying to screen and trying to advocate for more research in this area so that we can classify Parkinson’s disease as an ACE-related condition and thus give more resources from the mental health world, and also the social support world, to our patients.

Dr. LaFaver: Thank you. There are many important points, and I think it’s a very important thing to recognize that it may not be only trauma in childhood but also throughout life, as you said, and might really influence nonmotor symptoms of Parkinson’s disease in particular, including anxiety and pain, which are often difficult to treat.

I think there’s much more to do in research, advocacy, and education. We’re going to educate patients about this, and also educate other neurologists and providers. I think you mentioned that trauma-informed care is getting its spotlight in primary care and other specialties. I think we have catching up to do in neurology, and I think this is a really important work toward that goal.

Thank you so much for your work and for taking the time to share your thoughts. I hope to talk to you again soon.

Dr. Subramanian: Thank you so much, Kathrin.
 

Dr. LaFaver has disclosed no relevant financial relationships. Dr. Subramanian disclosed ties with Acorda Therapeutics.

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

A magnesium-rich diet has been linked to better brain health, an outcome that may help lower dementia risk, new research suggests.

Investigators studied more than 6,000 cognitively healthy individuals, aged 40-73, and found that those who consumed more than 550 mg of magnesium daily had a brain age approximately 1 year younger by age 55 years, compared with a person who consumed a normal magnesium intake (~360 mg per day).

“This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health,” lead author Khawlah Alateeq, a PhD candidate in neuroscience at Australian National University’s National Centre for Epidemiology and Population Health, said in an interview.

Clinicians “can use [the findings] to counsel patients on the benefits of increasing magnesium intake through a healthy diet and monitoring magnesium levels to prevent deficiencies,” she stated.

The study was published online  in the European Journal of Nutrition.
 

Promising target

The researchers were motivated to conduct the study because of “the growing concern over the increasing prevalence of dementia,” Ms. Alateeq said.

“Since there is no cure for dementia, and the development of pharmacological treatment for dementia has been unsuccessful over the last 30 years, prevention has been suggested as an effective approach to address the issue,” she added.

Nutrition, Ms. Alateeq said, is a “modifiable risk factor that can influence brain health and is highly amenable to scalable and cost-effective interventions.” It represents “a promising target” for risk reduction at a population level.

Previous research shows individuals with lower magnesium levels are at higher risk for AD, while those with higher dietary magnesium intake may be at lower risk of progressing from normal aging to cognitive impairment.

Most previous studies, however, included participants older than age 60 years, and it’s “unclear when the neuroprotective effects of dietary magnesium become detectable,” the researchers note.

Moreover, dietary patterns change and fluctuate, potentially leading to changes in magnesium intake over time. These changes may have as much impact as absolute magnesium at any point in time.

In light of the “current lack of understanding of when and to what extent dietary magnesium exerts its protective effects on the brain,” the researchers examined the association between magnesium trajectories over time, brain matter, and white matter lesions.

They also examined the association between magnesium and several different blood pressure measures (mean arterial pressure, systolic blood pressure, diastolic blood pressure, and pulse pressure).

Since cardiovascular health, neurodegeneration, and brain shrinkage patterns differ between men and women, the researchers stratified their analyses by sex.
 

Brain volume differences

The researchers analyzed the dietary magnesium intake of 6,001 individuals (mean age, 55.3 years) selected from the UK Biobank – a prospective cohort study of participants aged 37-73 at baseline, who were assessed between 2005 and 2023.

For the current study, only participants with baseline DBP and SBP measurements and structural MRI scans were included. Participants were also required to be free of neurologic disorders and to have an available record of dietary magnesium intake.

Covariates included age, sex, education, health conditions, smoking status, body mass index, amount of physical activity, smoking status, and alcohol intake.

Over a 16-month period, participants completed an online questionnaire five times. Their responses were used to calculate daily magnesium intake. Foods of particular interest included leafy green vegetables, legumes, nuts, seeds, and whole grains, all of which are magnesium rich.

They used latent class analysis (LCA) to “identify mutually exclusive subgroup (classes) of magnesium intake trajectory separately for men and women.”

Men had a slightly higher prevalence of BP medication and diabetes, compared with women, and postmenopausal women had a higher prevalence of BP medication and diabetes, compared with premenopausal women.

Compared with lower baseline magnesium intake, higher baseline dietary intake of magnesium was associated with larger brain volumes in several regions in both men and women.

The latent class analysis identified three classes of magnesium intake:

Association, not causation

Yuko Hara, PhD, director of Aging and Prevention, Alzheimer’s Drug Discovery Foundation, noted that the study is observational and therefore shows an association, not causation.

“People eating a high-magnesium diet may also be eating a brain-healthy diet and getting high levels of nutrients/minerals other than magnesium alone,” suggested Dr. Hara, who was not involved with the study.

She noted that many foods are good sources of magnesium, including spinach, almonds, cashews, legumes, yogurt, brown rice, and avocados.

“Eating a brain-healthy diet (for example, the Mediterranean diet) is one of the Seven Steps to Protect Your Cognitive Vitality that ADDF’s Cognitive Vitality promotes,” she said.

Open Access funding was enabled and organized by the Council of Australian University Librarians and its Member Institutions. Ms. Alateeq, her co-authors, and Dr. Hara declare no relevant financial relationships.

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

A magnesium-rich diet has been linked to better brain health, an outcome that may help lower dementia risk, new research suggests.

Investigators studied more than 6,000 cognitively healthy individuals, aged 40-73, and found that those who consumed more than 550 mg of magnesium daily had a brain age approximately 1 year younger by age 55 years, compared with a person who consumed a normal magnesium intake (~360 mg per day).

“This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health,” lead author Khawlah Alateeq, a PhD candidate in neuroscience at Australian National University’s National Centre for Epidemiology and Population Health, said in an interview.

Clinicians “can use [the findings] to counsel patients on the benefits of increasing magnesium intake through a healthy diet and monitoring magnesium levels to prevent deficiencies,” she stated.

The study was published online  in the European Journal of Nutrition.
 

Promising target

The researchers were motivated to conduct the study because of “the growing concern over the increasing prevalence of dementia,” Ms. Alateeq said.

“Since there is no cure for dementia, and the development of pharmacological treatment for dementia has been unsuccessful over the last 30 years, prevention has been suggested as an effective approach to address the issue,” she added.

Nutrition, Ms. Alateeq said, is a “modifiable risk factor that can influence brain health and is highly amenable to scalable and cost-effective interventions.” It represents “a promising target” for risk reduction at a population level.

Previous research shows individuals with lower magnesium levels are at higher risk for AD, while those with higher dietary magnesium intake may be at lower risk of progressing from normal aging to cognitive impairment.

Most previous studies, however, included participants older than age 60 years, and it’s “unclear when the neuroprotective effects of dietary magnesium become detectable,” the researchers note.

Moreover, dietary patterns change and fluctuate, potentially leading to changes in magnesium intake over time. These changes may have as much impact as absolute magnesium at any point in time.

In light of the “current lack of understanding of when and to what extent dietary magnesium exerts its protective effects on the brain,” the researchers examined the association between magnesium trajectories over time, brain matter, and white matter lesions.

They also examined the association between magnesium and several different blood pressure measures (mean arterial pressure, systolic blood pressure, diastolic blood pressure, and pulse pressure).

Since cardiovascular health, neurodegeneration, and brain shrinkage patterns differ between men and women, the researchers stratified their analyses by sex.
 

Brain volume differences

The researchers analyzed the dietary magnesium intake of 6,001 individuals (mean age, 55.3 years) selected from the UK Biobank – a prospective cohort study of participants aged 37-73 at baseline, who were assessed between 2005 and 2023.

For the current study, only participants with baseline DBP and SBP measurements and structural MRI scans were included. Participants were also required to be free of neurologic disorders and to have an available record of dietary magnesium intake.

Covariates included age, sex, education, health conditions, smoking status, body mass index, amount of physical activity, smoking status, and alcohol intake.

Over a 16-month period, participants completed an online questionnaire five times. Their responses were used to calculate daily magnesium intake. Foods of particular interest included leafy green vegetables, legumes, nuts, seeds, and whole grains, all of which are magnesium rich.

They used latent class analysis (LCA) to “identify mutually exclusive subgroup (classes) of magnesium intake trajectory separately for men and women.”

Men had a slightly higher prevalence of BP medication and diabetes, compared with women, and postmenopausal women had a higher prevalence of BP medication and diabetes, compared with premenopausal women.

Compared with lower baseline magnesium intake, higher baseline dietary intake of magnesium was associated with larger brain volumes in several regions in both men and women.

The latent class analysis identified three classes of magnesium intake:

Association, not causation

Yuko Hara, PhD, director of Aging and Prevention, Alzheimer’s Drug Discovery Foundation, noted that the study is observational and therefore shows an association, not causation.

“People eating a high-magnesium diet may also be eating a brain-healthy diet and getting high levels of nutrients/minerals other than magnesium alone,” suggested Dr. Hara, who was not involved with the study.

She noted that many foods are good sources of magnesium, including spinach, almonds, cashews, legumes, yogurt, brown rice, and avocados.

“Eating a brain-healthy diet (for example, the Mediterranean diet) is one of the Seven Steps to Protect Your Cognitive Vitality that ADDF’s Cognitive Vitality promotes,” she said.

Open Access funding was enabled and organized by the Council of Australian University Librarians and its Member Institutions. Ms. Alateeq, her co-authors, and Dr. Hara declare no relevant financial relationships.

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

A magnesium-rich diet has been linked to better brain health, an outcome that may help lower dementia risk, new research suggests.

Investigators studied more than 6,000 cognitively healthy individuals, aged 40-73, and found that those who consumed more than 550 mg of magnesium daily had a brain age approximately 1 year younger by age 55 years, compared with a person who consumed a normal magnesium intake (~360 mg per day).

“This research highlights the potential benefits of a diet high in magnesium and the role it plays in promoting good brain health,” lead author Khawlah Alateeq, a PhD candidate in neuroscience at Australian National University’s National Centre for Epidemiology and Population Health, said in an interview.

Clinicians “can use [the findings] to counsel patients on the benefits of increasing magnesium intake through a healthy diet and monitoring magnesium levels to prevent deficiencies,” she stated.

The study was published online  in the European Journal of Nutrition.
 

Promising target

The researchers were motivated to conduct the study because of “the growing concern over the increasing prevalence of dementia,” Ms. Alateeq said.

“Since there is no cure for dementia, and the development of pharmacological treatment for dementia has been unsuccessful over the last 30 years, prevention has been suggested as an effective approach to address the issue,” she added.

Nutrition, Ms. Alateeq said, is a “modifiable risk factor that can influence brain health and is highly amenable to scalable and cost-effective interventions.” It represents “a promising target” for risk reduction at a population level.

Previous research shows individuals with lower magnesium levels are at higher risk for AD, while those with higher dietary magnesium intake may be at lower risk of progressing from normal aging to cognitive impairment.

Most previous studies, however, included participants older than age 60 years, and it’s “unclear when the neuroprotective effects of dietary magnesium become detectable,” the researchers note.

Moreover, dietary patterns change and fluctuate, potentially leading to changes in magnesium intake over time. These changes may have as much impact as absolute magnesium at any point in time.

In light of the “current lack of understanding of when and to what extent dietary magnesium exerts its protective effects on the brain,” the researchers examined the association between magnesium trajectories over time, brain matter, and white matter lesions.

They also examined the association between magnesium and several different blood pressure measures (mean arterial pressure, systolic blood pressure, diastolic blood pressure, and pulse pressure).

Since cardiovascular health, neurodegeneration, and brain shrinkage patterns differ between men and women, the researchers stratified their analyses by sex.
 

Brain volume differences

The researchers analyzed the dietary magnesium intake of 6,001 individuals (mean age, 55.3 years) selected from the UK Biobank – a prospective cohort study of participants aged 37-73 at baseline, who were assessed between 2005 and 2023.

For the current study, only participants with baseline DBP and SBP measurements and structural MRI scans were included. Participants were also required to be free of neurologic disorders and to have an available record of dietary magnesium intake.

Covariates included age, sex, education, health conditions, smoking status, body mass index, amount of physical activity, smoking status, and alcohol intake.

Over a 16-month period, participants completed an online questionnaire five times. Their responses were used to calculate daily magnesium intake. Foods of particular interest included leafy green vegetables, legumes, nuts, seeds, and whole grains, all of which are magnesium rich.

They used latent class analysis (LCA) to “identify mutually exclusive subgroup (classes) of magnesium intake trajectory separately for men and women.”

Men had a slightly higher prevalence of BP medication and diabetes, compared with women, and postmenopausal women had a higher prevalence of BP medication and diabetes, compared with premenopausal women.

Compared with lower baseline magnesium intake, higher baseline dietary intake of magnesium was associated with larger brain volumes in several regions in both men and women.

The latent class analysis identified three classes of magnesium intake:

Association, not causation

Yuko Hara, PhD, director of Aging and Prevention, Alzheimer’s Drug Discovery Foundation, noted that the study is observational and therefore shows an association, not causation.

“People eating a high-magnesium diet may also be eating a brain-healthy diet and getting high levels of nutrients/minerals other than magnesium alone,” suggested Dr. Hara, who was not involved with the study.

She noted that many foods are good sources of magnesium, including spinach, almonds, cashews, legumes, yogurt, brown rice, and avocados.

“Eating a brain-healthy diet (for example, the Mediterranean diet) is one of the Seven Steps to Protect Your Cognitive Vitality that ADDF’s Cognitive Vitality promotes,” she said.

Open Access funding was enabled and organized by the Council of Australian University Librarians and its Member Institutions. Ms. Alateeq, her co-authors, and Dr. Hara declare no relevant financial relationships.

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

This transcript has been edited for clarity.

Few diseases have stymied explanation like autism spectrum disorder (ASD). We know that the prevalence has been increasing dramatically, but we aren’t quite sure whether that is because of more screening and awareness or more fundamental changes. We know that much of the risk appears to be genetic, but there may be 1,000 genes involved in the syndrome. We know that certain environmental exposures, like pollution, might increase the risk – perhaps on a susceptible genetic background – but we’re not really sure which exposures are most harmful.

So, the search continues, across all domains of inquiry from cell culture to large epidemiologic analyses. And this week, a new player enters the field, and, as they say, it’s something in the water.

Does exposure to lithium in groundwater cause autism?

We’re talking about this paper, by Zeyan Liew and colleagues, appearing in JAMA Pediatrics.

Using the incredibly robust health data infrastructure in Denmark, the researchers were able to identify 8,842 children born between 2000 and 2013 with ASD and matched each one to five control kids of the same sex and age without autism.

They then mapped the location the mothers of these kids lived while they were pregnant – down to 5 meters resolution, actually – to groundwater lithium levels.

International Journal of Environmental Research and Public Health

JAMA Pediatrics

Dr. F. Perry Wilson

U.S. Geological Survey

Global Burden of Disease Collaborative Network

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. He has disclosed no relevant financial relationships. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his new book, “How Medicine Works and When It Doesn’t”, is available now.

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

This transcript has been edited for clarity.

Few diseases have stymied explanation like autism spectrum disorder (ASD). We know that the prevalence has been increasing dramatically, but we aren’t quite sure whether that is because of more screening and awareness or more fundamental changes. We know that much of the risk appears to be genetic, but there may be 1,000 genes involved in the syndrome. We know that certain environmental exposures, like pollution, might increase the risk – perhaps on a susceptible genetic background – but we’re not really sure which exposures are most harmful.

So, the search continues, across all domains of inquiry from cell culture to large epidemiologic analyses. And this week, a new player enters the field, and, as they say, it’s something in the water.

Does exposure to lithium in groundwater cause autism?

We’re talking about this paper, by Zeyan Liew and colleagues, appearing in JAMA Pediatrics.

Using the incredibly robust health data infrastructure in Denmark, the researchers were able to identify 8,842 children born between 2000 and 2013 with ASD and matched each one to five control kids of the same sex and age without autism.

They then mapped the location the mothers of these kids lived while they were pregnant – down to 5 meters resolution, actually – to groundwater lithium levels.

International Journal of Environmental Research and Public Health

JAMA Pediatrics

Dr. F. Perry Wilson

U.S. Geological Survey

Global Burden of Disease Collaborative Network

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. He has disclosed no relevant financial relationships. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his new book, “How Medicine Works and When It Doesn’t”, is available now.

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

This transcript has been edited for clarity.

Few diseases have stymied explanation like autism spectrum disorder (ASD). We know that the prevalence has been increasing dramatically, but we aren’t quite sure whether that is because of more screening and awareness or more fundamental changes. We know that much of the risk appears to be genetic, but there may be 1,000 genes involved in the syndrome. We know that certain environmental exposures, like pollution, might increase the risk – perhaps on a susceptible genetic background – but we’re not really sure which exposures are most harmful.

So, the search continues, across all domains of inquiry from cell culture to large epidemiologic analyses. And this week, a new player enters the field, and, as they say, it’s something in the water.

Does exposure to lithium in groundwater cause autism?

We’re talking about this paper, by Zeyan Liew and colleagues, appearing in JAMA Pediatrics.

Using the incredibly robust health data infrastructure in Denmark, the researchers were able to identify 8,842 children born between 2000 and 2013 with ASD and matched each one to five control kids of the same sex and age without autism.

They then mapped the location the mothers of these kids lived while they were pregnant – down to 5 meters resolution, actually – to groundwater lithium levels.

International Journal of Environmental Research and Public Health

JAMA Pediatrics

Dr. F. Perry Wilson

U.S. Geological Survey

Global Burden of Disease Collaborative Network

F. Perry Wilson, MD, MSCE, is an associate professor of medicine and director of Yale’s Clinical and Translational Research Accelerator. He has disclosed no relevant financial relationships. His science communication work can be found in the Huffington Post, on NPR, and here on Medscape. He tweets @fperrywilson and his new book, “How Medicine Works and When It Doesn’t”, is available now.

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

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy

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

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy

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

Researchers have identified specific regions of the brain that appear to be damaged by high blood pressure. The finding may explain the link between hypertension and cognitive impairment.

They used genetic information from genome-wide association studies (GWASs) and MRI scans of the brain to study the relationship between hypertension, changes in brain structures, and cognitive impairment. Using Mendelian randomization techniques, they identified nine brain structures related to cognitive impairment that are affected by blood pressure.

Dr Lorenzo Carnevale, IRCCS INM Neuromed, Pozzilli, Italy

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

Younger people who experience stroke or intracerebral hemorrhage have about a three- to fivefold increased risk of being diagnosed with cancer in the next few years, new research shows.

In young people, stroke might be the first manifestation of an underlying cancer, according to the investigators, led by Jamie Verhoeven, MD, PhD, with the department of neurology, Radboud University Medical Centre, Nijmegen, the Netherlands.

The new study can be viewed as a “stepping stone for future studies investigating the usefulness of screening for cancer after stroke,” the researchers say.

The study was published online in JAMA Network Open.

Currently, the diagnostic workup for young people with stroke includes searching for rare clotting disorders, although screening for cancer is not regularly performed.

Some research suggests that stroke and cancer are linked, but the literature is limited. In prior studies among people of all ages, cancer incidence after stroke has been variable – from 1% to 5% at 1 year and from 11% to 30% after 10 years.

To the team’s knowledge, only two studies have described the incidence of cancer after stroke among younger patients. One put the risk at 0.5% for people aged 18-50 years in the first year after stroke; the other described a cumulative risk of 17.3% in the 10 years after stroke for patients aged 18-55 years.

Using Dutch data, Dr. Verhoeven and colleagues identified 27,616 young stroke patients (age, 15-49 years; median age, 45 years) and 362,782 older stroke patients (median age, 76 years).

The cumulative incidence of any new cancer at 10 years was 3.7% among the younger stroke patients and 8.5% among the older stroke patients.

The incidence of a new cancer after stroke among younger patients was higher among women than men, while the opposite was true for older stroke patients.

Compared with the general population, younger stroke patients had a more than 2.5-fold greater likelihood of being diagnosed with a new cancer in the first year after ischemic stroke (standardized incidence ratio, 2.6). The risk was highest for lung cancer (SIR, 6.9), followed by hematologic cancers (SIR, 5.2).

Compared with the general population, younger stroke patients had nearly a 5.5-fold greater likelihood of being diagnosed with a new cancer in the first year after intracerebral hemorrhage (SIR, 5.4), and the risk was highest for hematologic cancers (SIR, 14.2).

In younger patients, the cumulative incidence of any cancer decreased over the years but remained significantly higher for 8 years following a stroke.

For patients aged 50 years or older, the 1-year risk for any new cancer after either ischemic stroke or intracerebral hemorrhage was 1.2 times higher, compared with the general population.

“We typically think of occult cancer as being a cause of stroke in an older population, given that the incidence of cancer increases over time [but] what this study shows is that we probably do need to consider occult cancer as an underlying cause of stroke even in a younger population,” said Laura Gioia, MD, stroke neurologist at the University of Montreal, who was not involved in the research.

Dr. Verhoeven and colleagues conclude that their finding supports the hypothesis of a causal link between cancer and stroke. Given the timing between stroke and cancer diagnosis, cancer may have been present when the stroke occurred and possibly played a role in causing it, the authors note. However, conclusions on causal mechanisms cannot be drawn from the current study.

The question of whether young stroke patients should be screened for cancer is a tough one, Dr. Gioia noted. “Cancer represents a small percentage of causes of stroke. That means you would have to screen a lot of people with a benefit that is still uncertain for the moment,” Dr. Gioia said in an interview.

“I think we need to keep cancer in mind as a cause of stroke in our young patients, and that should probably guide our history-taking with the patient and consider imaging when it’s appropriate and when we think that there could be an underlying occult cancer,” Dr. Gioia suggested.

The study was funded in part through unrestricted funding by Stryker, Medtronic, and Cerenovus. Dr. Verhoeven and Dr. Gioia have disclosed no relevant financial relationships.

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

Younger people who experience stroke or intracerebral hemorrhage have about a three- to fivefold increased risk of being diagnosed with cancer in the next few years, new research shows.

In young people, stroke might be the first manifestation of an underlying cancer, according to the investigators, led by Jamie Verhoeven, MD, PhD, with the department of neurology, Radboud University Medical Centre, Nijmegen, the Netherlands.

The new study can be viewed as a “stepping stone for future studies investigating the usefulness of screening for cancer after stroke,” the researchers say.

The study was published online in JAMA Network Open.

Currently, the diagnostic workup for young people with stroke includes searching for rare clotting disorders, although screening for cancer is not regularly performed.

Some research suggests that stroke and cancer are linked, but the literature is limited. In prior studies among people of all ages, cancer incidence after stroke has been variable – from 1% to 5% at 1 year and from 11% to 30% after 10 years.

To the team’s knowledge, only two studies have described the incidence of cancer after stroke among younger patients. One put the risk at 0.5% for people aged 18-50 years in the first year after stroke; the other described a cumulative risk of 17.3% in the 10 years after stroke for patients aged 18-55 years.

Using Dutch data, Dr. Verhoeven and colleagues identified 27,616 young stroke patients (age, 15-49 years; median age, 45 years) and 362,782 older stroke patients (median age, 76 years).

The cumulative incidence of any new cancer at 10 years was 3.7% among the younger stroke patients and 8.5% among the older stroke patients.

The incidence of a new cancer after stroke among younger patients was higher among women than men, while the opposite was true for older stroke patients.

Compared with the general population, younger stroke patients had a more than 2.5-fold greater likelihood of being diagnosed with a new cancer in the first year after ischemic stroke (standardized incidence ratio, 2.6). The risk was highest for lung cancer (SIR, 6.9), followed by hematologic cancers (SIR, 5.2).

Compared with the general population, younger stroke patients had nearly a 5.5-fold greater likelihood of being diagnosed with a new cancer in the first year after intracerebral hemorrhage (SIR, 5.4), and the risk was highest for hematologic cancers (SIR, 14.2).

In younger patients, the cumulative incidence of any cancer decreased over the years but remained significantly higher for 8 years following a stroke.

For patients aged 50 years or older, the 1-year risk for any new cancer after either ischemic stroke or intracerebral hemorrhage was 1.2 times higher, compared with the general population.

“We typically think of occult cancer as being a cause of stroke in an older population, given that the incidence of cancer increases over time [but] what this study shows is that we probably do need to consider occult cancer as an underlying cause of stroke even in a younger population,” said Laura Gioia, MD, stroke neurologist at the University of Montreal, who was not involved in the research.

Dr. Verhoeven and colleagues conclude that their finding supports the hypothesis of a causal link between cancer and stroke. Given the timing between stroke and cancer diagnosis, cancer may have been present when the stroke occurred and possibly played a role in causing it, the authors note. However, conclusions on causal mechanisms cannot be drawn from the current study.

The question of whether young stroke patients should be screened for cancer is a tough one, Dr. Gioia noted. “Cancer represents a small percentage of causes of stroke. That means you would have to screen a lot of people with a benefit that is still uncertain for the moment,” Dr. Gioia said in an interview.

“I think we need to keep cancer in mind as a cause of stroke in our young patients, and that should probably guide our history-taking with the patient and consider imaging when it’s appropriate and when we think that there could be an underlying occult cancer,” Dr. Gioia suggested.

The study was funded in part through unrestricted funding by Stryker, Medtronic, and Cerenovus. Dr. Verhoeven and Dr. Gioia have disclosed no relevant financial relationships.

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

Younger people who experience stroke or intracerebral hemorrhage have about a three- to fivefold increased risk of being diagnosed with cancer in the next few years, new research shows.

In young people, stroke might be the first manifestation of an underlying cancer, according to the investigators, led by Jamie Verhoeven, MD, PhD, with the department of neurology, Radboud University Medical Centre, Nijmegen, the Netherlands.

The new study can be viewed as a “stepping stone for future studies investigating the usefulness of screening for cancer after stroke,” the researchers say.

The study was published online in JAMA Network Open.

Currently, the diagnostic workup for young people with stroke includes searching for rare clotting disorders, although screening for cancer is not regularly performed.

Some research suggests that stroke and cancer are linked, but the literature is limited. In prior studies among people of all ages, cancer incidence after stroke has been variable – from 1% to 5% at 1 year and from 11% to 30% after 10 years.

To the team’s knowledge, only two studies have described the incidence of cancer after stroke among younger patients. One put the risk at 0.5% for people aged 18-50 years in the first year after stroke; the other described a cumulative risk of 17.3% in the 10 years after stroke for patients aged 18-55 years.

Using Dutch data, Dr. Verhoeven and colleagues identified 27,616 young stroke patients (age, 15-49 years; median age, 45 years) and 362,782 older stroke patients (median age, 76 years).

The cumulative incidence of any new cancer at 10 years was 3.7% among the younger stroke patients and 8.5% among the older stroke patients.

The incidence of a new cancer after stroke among younger patients was higher among women than men, while the opposite was true for older stroke patients.

Compared with the general population, younger stroke patients had a more than 2.5-fold greater likelihood of being diagnosed with a new cancer in the first year after ischemic stroke (standardized incidence ratio, 2.6). The risk was highest for lung cancer (SIR, 6.9), followed by hematologic cancers (SIR, 5.2).

Compared with the general population, younger stroke patients had nearly a 5.5-fold greater likelihood of being diagnosed with a new cancer in the first year after intracerebral hemorrhage (SIR, 5.4), and the risk was highest for hematologic cancers (SIR, 14.2).

In younger patients, the cumulative incidence of any cancer decreased over the years but remained significantly higher for 8 years following a stroke.

For patients aged 50 years or older, the 1-year risk for any new cancer after either ischemic stroke or intracerebral hemorrhage was 1.2 times higher, compared with the general population.

“We typically think of occult cancer as being a cause of stroke in an older population, given that the incidence of cancer increases over time [but] what this study shows is that we probably do need to consider occult cancer as an underlying cause of stroke even in a younger population,” said Laura Gioia, MD, stroke neurologist at the University of Montreal, who was not involved in the research.

Dr. Verhoeven and colleagues conclude that their finding supports the hypothesis of a causal link between cancer and stroke. Given the timing between stroke and cancer diagnosis, cancer may have been present when the stroke occurred and possibly played a role in causing it, the authors note. However, conclusions on causal mechanisms cannot be drawn from the current study.

The question of whether young stroke patients should be screened for cancer is a tough one, Dr. Gioia noted. “Cancer represents a small percentage of causes of stroke. That means you would have to screen a lot of people with a benefit that is still uncertain for the moment,” Dr. Gioia said in an interview.

“I think we need to keep cancer in mind as a cause of stroke in our young patients, and that should probably guide our history-taking with the patient and consider imaging when it’s appropriate and when we think that there could be an underlying occult cancer,” Dr. Gioia suggested.

The study was funded in part through unrestricted funding by Stryker, Medtronic, and Cerenovus. Dr. Verhoeven and Dr. Gioia have disclosed no relevant financial relationships.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Cluster headache and migraine have strong ties to the circadian system at multiple levels, say new findings that could have significant treatment implications.

A meta-analysis of 16 studies showed a circadian pattern in 71% of cluster headache attacks (3,490 of 4,953), with a clear circadian peak between 9:00 p.m. and 3:00 a.m.

Migraine was also associated with a circadian pattern in 50% of cases (2,698 of 5,385) across eight studies, with a clear circadian trough between 11:00 p.m. and 7:00 a.m.

Seasonal peaks were also evident for cluster headache (spring and autumn) and migraine (April to October).

“In the short term, these findings help us explain the timing to patients – for example, it is possible that a headache at 8 a.m. is due to their internal body clock instead of their pillow, or breakfast food, or morning medications,” lead investigator Mark Burish, MD, PhD, associate professor, department of neurosurgery, at University of Texas Health Houston, told this news organization.

“In the long term, these findings do suggest that medications that target the circadian system could be effective in migraine and headache patients,” Dr. Burish added.

The study was published online in Neurology.


 

Treatment implications?

Across studies, chronotype was “highly variable” for both cluster headache and migraine, the investigators report.

Cluster headache was associated with lower melatonin and higher cortisol levels, compared with non–cluster headache controls.

On a genetic level, cluster headache was associated with two core circadian genes (CLOCK and REV-ERB–alpha), and five of the nine genes that increase the likelihood of having cluster headache are genes with a circadian pattern of expression.

Migraine headache was associated with lower urinary melatonin levels and with the core circadian genes, CK1-delta and ROR-alpha, and 110 of the 168 genes associated with migraine were clock-controlled genes.

“The data suggest that both of these headache disorders are highly circadian at multiple levels, especially cluster headache,” Dr. Burish said in a release.

“This reinforces the importance of the hypothalamus – the area of the brain that houses the primary biological clock – and its role in cluster headache and migraine. It also raises the question of the genetics of triggers such as sleep changes that are known triggers for migraine and are cues for the body’s circadian rhythm,” Dr. Burish said.

“We hope that future research will look into circadian medications as a new treatment option for migraine and cluster headache patients,” Dr. Burish told this news organization.
 

Importance of sleep regulation

The authors of an accompanying editorial note that even though the study doesn’t have immediate clinical implications, it offers a better understanding of the way chronobiologic factors may influence treatment.

“At a minimum, interventions known to regulate and improve sleep (e.g., melatonin, cognitive behavioral therapy), and which are safe and straightforward to introduce, may be useful in some individuals susceptible to circadian misalignment or sleep disorders,” write Heidi Sutherland, PhD, and Lyn Griffiths, PhD, with Queensland University of Technology, Brisbane, Australia.

“Treatment of comorbidities (e.g., insomnia) that result in sleep disturbances may also help headache management. Furthermore, chronobiological aspects of any pharmacological interventions should be considered, as some frequently used headache and migraine drugs can modulate circadian cycles and influence the expression of circadian genes (e.g., verapamil), or have sleep-related side effects,” they add.

A limitation of the study was the lack of information on factors that could influence the circadian cycle, such as medications; other disorders, such as bipolar disorder; or circadian rhythm issues, such as night-shift work.

The study was supported by grants from the Japan Society for the Promotion of Science, the National Institutes of Health, The Welch Foundation, and The Will Erwin Headache Research Foundation. Dr. Burish is an unpaid member of the medical advisory board of Clusterbusters, and a site investigator for a cluster headache clinical trial funded by Lundbeck. Dr. Sutherland has received grant funding from the U.S. Migraine Research Foundation, and received institute support from Queensland University of Technology for genetics research. Dr. Griffiths has received grant funding from the Australian NHMRC, U.S. Department of Defense, and the U.S. Migraine Research Foundation, and consultancy funding from TEVA.

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

Ms. A, age 48, is a physician’s assistant with no psychiatric history. She presents to the emergency department (ED) with her partner and daughter due to a 15-minute episode of acute-onset memory loss and concern for stroke. In the ED, Ms. A is confused and repeatedly asks, “Where are we?” “How did we get here?” and “What day is it?” Her partner denies Ms. A has focal neurologic deficits or seizures.

Ms. A had only slept 4 hours the night before she came to the ED because she had just learned that her daughter works in the sex industry. According to her daughter, Ms. A was raped by a soldier many years ago. At that time, her perpetrator told Ms. A that he would kill her entire family if she ever told anyone. As a result, she never pursued any psychological or psychiatric treatment.

During the evaluation, Ms. A shares details regarding her social and medical history; however, she does not recall receiving bad news the night before. She asks the interviewer several times how she got to the hospital, and when a cranial nerve exam is performed, she states, “I am not the patient!”

Ms. A’s vital signs and physical exam are unremarkable. Urinalysis is significant for a ketones level of 20 mmol/L (reference range: negative for ketones), and a urine human chorionic gonadotropin test is negative. A neurologic exam does not identify any focal deficits. No imaging is performed.

Transient global amnesia (TGA) describes an episode of anterograde, and possibly retrograde, amnesia that lasts up to 24 hours. On presentation, patients experiencing TGA repeatedly ask, “Where am I?” “What day is it?” and “How did I get here?” However, semantic memory—such as knowledge of the world and autobiographical information—is preserved.¹ The first case of TGA was described in 1956, and its diagnostic criteria were most recently modified in 1990 (Table²).

Though TGA is the most common cause of acute-onset amnesia, it is rare, affecting approximately 3 to 10 individuals per 100,000. The average age of onset is 61 to 63, with most cases occurring after age 50. TGA is generally thought to affect males and females equally, though some studies suggest a female predominance.³ In most cases (approximately 90%), there is a precipitating event such as physical or emotional stress, change in temperature, or sexual intercourse.⁴

In this article, we provide an overview of the classification, presentation, differential diagnosis, workup, and treatment of TGA. While TGA is a neurologic diagnosis, in a subset of patients it can present with psychiatric features resembling conversion disorder. For such patients, we argue that TGA can be considered a neuropsychiatric condition (Box 1^5-12). This classification may empower emergency psychiatry clinicians and psychotherapists to identify and treat the condition, which is not described by the current psychiatric diagnostic system.

Box 1

Continue to: Differential diagnosis and workup

The differential diagnosis for acute-onset memory loss in the absence of other neurologic or psychiatric features is broad. It includes:

• dissociative amnesia
• ischemic amnesia
• transient epileptic amnesia
• toxic and metabolic amnesia
• posttraumatic amnesia.

Dissociative amnesia (DA), otherwise known as psychogenic amnesia, is “an inability to recall important autobiographical information, usually of a traumatic or stressful nature, that is inconsistent with ordinary forgetting.”¹³ According to this definition, DA features only retro­grade amnesia, as opposed to TGA, which features anterograde amnesia, with possible retrograde amnesia. A subtype of DA—specifically, “continuous amnesia” or “anterograde dissociative amnesia”— is in DSM-5.¹³ However, the diagnostic criteria are unclear, and no cases have been identified in the literature since 1903, before TGA became a diagnostic entity.^5,14 Moreover, patients with DA cannot recall autobiographical information, which is not a feature of TGA. Within DSM-5, TGA is an exclusion criterion for DA.¹³ Thus, an episode of anterograde amnesia with acute onset best meets criteria for TGA, even if there are substantial psychiatric risk factors.

Ischemic amnesia—including stroke and transient ischemic attack (TIA)—is often the primary concern of patients with TGA and their families upon initial presentation, as was the case with Ms. A.^6,15 TIA presenting with isolated, acute-onset amnesia would be highly unusual, because these attacks usually present with focal symptoms including motor deficits, sensory deficits, visual field deficits, and aphasia or dysarthria. A patient with amnesia experiencing a TIA would likely have symptoms lasting from seconds to minutes, which is much shorter than a typical TGA episode.¹⁶

Amnesia secondary to stroke may be transient or permanent.⁷ Amnesia is present in approximately 1% of all strokes and in approximately 19.3% of posterior cerebral artery strokes.^7,17 Unlike TIA and TGA, ischemic amnesia would present with MRI findings detectable at symptom onset. TGA does reveal MRI findings, particularly punctate lesions in the CA1 area of the hippocampus; however, these lesions are typically much smaller than those found in stroke, and are not detectable until 12 to 48 hours after episode onset.^1,17 MRI findings in ischemic amnesia are typically associated with extrahippocampal lesions.¹⁷ Finally, the presence of vascular risk factors such as hyperlipidemia, smoking, diabetes, and hypertension may also favor a diagnosis of stroke or TIA as opposed to TGA, which is not associated with these risk factors.¹⁸ Though ischemic amnesia and TGA usually can be differentiated based on history and presentation, MRI with fluid-attenuated inversion recovery and diffusion-weighted imaging may be performed to definitively distinguish stroke from TGA.⁷

Transient epileptic amnesia (TEA), a focal form of epilepsy within the temporal lobe, should also be considered in patients who present with acute-onset amnesia. Like TGA, TEA may present with simultaneous anterograde and retrograde amnesia accompanied by repetitive questioning.¹⁹ Amnesia can be the sole symptom of TEA in up to 24% of cases. However, several key features distinguish TEA from TGA. TEA most often presents with other clinical signs of seizures, such as oral automatisms and/or olfactory hallucinations.²⁰ There is also a significant difference in episode length; TEA episodes last an average of 30 to 60 minutes and tend to occur upon wakening, whereas TGA episodes last an average of 4 to 6 hours and do not preferentially occur at any particular time.^1,21 In the interictal period—between seizures—patients with TEA may also experience accelerated long-term forgetting, autobiographical amnesia, and topographical amnesia.^19,20 Finally, a diagnosis of TEA also requires recurrent episodes. Recurrence can happen with TGA, but is less frequent.²¹ Generally, history and presentation can distinguish TEA from TGA. Though there is no formal protocol for TEA workup, Lanzone et al²¹ recommend 24-hour EEG or EEG sleep monitoring in patients who present with amnesia as well as other clinical manifestations of epileptic phenomenon.

Continue to: Toxic and metabolic

Toxic and metabolic etiologies of amnesia include opioid and cocaine use, general anesthetics,²² and hypoglycemia.^7,23 Toxic and metabolic causes of amnesia may mirror TGA in their acute onset as well as anterograde nature. However, these patients will likely present with fluctuating consciousness and/or other neuropsychiatric features, such as pressured speech, delusions, and/or distractability.²³ Obtaining a patient’s medical history, including substance use, medication use, and the presence of diabetes,²⁴ is typically sufficient to rule out toxic and metabolic causes.⁷

Posttraumatic amnesia (PTA) describes transient memory loss that occurs after a traumatic brain injury. Anterograde amnesia is most common, though approximately 20% of patients may also experience retro­grade amnesia pertaining to the events near the date of their injury. Unlike TGA, which typically resolves within 24 hours, the recovery time of amnestic symptoms in PTA ranges from minutes to years.⁷ A distinguishing feature of PTA is the presence of confusion, which often resembles a state of delirium.²⁵ The presentation of PTA can vary immensely with regards to agitation, psychotic symptoms, and the time to resolution of the amnesia. Though TGA can be distinguished from PTA based on a lack of clouding of consciousness, a case of anterograde amnesia warrants inquiry into a potential history of head injuries to rule out a traumatic cause.²⁶

Box 2^1,3,23,27-33 outlines current theories of the etiology and pathogenesis of TGA.

Box 2

Transient global ischemia: Psychiatric features

Several studies have demonstrated psychiatric precipitants, features, and comorbidities associated with TGA. Of the TGA cases associated with precipitating events, 29% to 50% are associated with an emotional stressor.^3,4 Examples of emotional stressors include a quarrel,⁴ the announcement of a birth or suicide, and a nightmare.¹⁵ For Ms. A, learning her daughter worked in the sex industry was an emotional stressor.²

During its acute phase, TGA has been shown to present with mood and anxiety symptoms.³⁴ Moreover, during episodes, patients often demonstrate features of panic attacks, such as dizziness, fainting, choking, palpitations, and paresthesia.^3,35

Continue to: Finally, patients with TGA...

Finally, patients with TGA are more likely to have psychiatric comorbidities than those without the condition. In a study of 25 patients who experienced TGA triggered by a precipitant, Inzitari et al⁴ found a strong association of TGA with phobic personality traits, including agoraphobia and simple phobic attitudes (ie, fear of traveling far from home or the sight of blood). Pantoni et al³⁵ replicated these results in 2005 and found that in comparison to patients with TIA, patients with TGA are more likely to have personal and family histories of psychiatric disease. A 2014 study by Dohring et al³⁶ found that compared to healthy controls, patients with TGA are more likely to have maladaptive coping strategies and stress responses. Patients with TGA tended to exhibit increased feelings of guilt, take more medication, and exhibit more anxiety compared to healthy controls.³⁶

Treatment: Benzodiazepines

There are no published treatment guidelines for TGA. However, in case reports, benzodiazepines (specifically lorazepam³⁷) have been shown to have utility in diagnosing and treating DA. The success of benzodiazepines is attributed to its gamma-aminobutyric acid mechanism, which involves inhibiting activity of the N-methyl-D-aspartate (NMDA) receptor, thereby reversing amnesia.³⁷ The NMDA receptor is also implicated in the stress theory of TGA. Though TGA typically resolves on its own within 24 hours, given the distressing nature of this disorder, benzodiazepines may be a suitable option to hasten memory improvement, particularly in patients with psychiatric risk factors.

However, the benzodiazepine midazolam has been identified as a precipitant of TGA. In a case report, Rinehart et al²² identified flumazenil—a benzodiazepine antagonist used primarily to treat retrograde postoperative amnesia—as an antidote. The potentially paradoxical role of benzodiazepines in both the precipitation and treatment of TGA may relate back to the heterogeneity of the etiologies of TGA. Further research comparing the treatment of TGA in patients with stress-induced TGA vs postoperative TGA is needed to better understand the neurochemical basis of TGA and work toward establishing optimal treatment options for different patient demographics.

A generally favorable prognosis

TGA carries a low risk of recurrence. In studies with 3- to 7-year follow-up periods, the recurrence rates ranged from 1.4% to 23.8%.^23,35,38

Memory impairments may be present for 5 to 6 months following a TGA episode. The severity of these impairments may range from clinically unnoticeable to the patient meeting the criteria for mild cognitive impairment.^23,39 The risk is higher in patients who have had recurrent TGA compared to those patients who have experienced only a single episode.²³

Continue to: TGA does not increase...

TGA does not increase the risk of cerebrovascular events. There is controversy regarding a potentially increased risk for dementia as well as epilepsy, though there is insufficient evidence to support these findings.^23,40

CASE CONTINUED

Five hours after the onset of Ms. A’s symptoms, the treatment team initiates oral lorazepam 1 mg. One hour after taking lorazepam, Ms. A’s anterograde and retrograde amnesia improve. She cannot recall why she was brought to the hospital but does remember the date and location, which she was not able to do on initial presentation. She feels safe, states a clear plan for self-care, and is discharged in the care of her partner. Though Ms. A’s memory improved soon after she received lorazepam, this improvement also could be attributed to the natural course of time, as TGA tends to resolve on its own within 24 hours.

Bottom Line

Transient global amnesia (TGA) is an episode of anterograde, and possibly retrograde, amnesia that lasts up to 24 hours. It represents an interesting diagnosis at the intersection of psychiatry and neurology. TGA has many established psychiatric risk factors and features—some of which may resemble conversion disorder—but these may only apply to a particular subset of patients, which reflects the heterogeneity of the condition.

Related Resources

• Sparaco M, Pascarella R, Muccio CF, et al. Forgetting the unforgettable: transient global amnesia part I: pathophysiology and etiology. J Clin Med. 2022;11(12): 3373. doi:10.3390/jcm1112337
• Sparaco M, Pascarella R, Muccio CF, et al. Forgetting the unforgettable: transient global amnesia part II: a clinical road map. J Clin Med. 2022;11(14):3940. doi:10.3390/ jcm11143940

Drug Brand Names

Flumazenil • Romazicon
Lorazepam • Ativan
Midazolam • Versed

Ms. A, age 48, is a physician’s assistant with no psychiatric history. She presents to the emergency department (ED) with her partner and daughter due to a 15-minute episode of acute-onset memory loss and concern for stroke. In the ED, Ms. A is confused and repeatedly asks, “Where are we?” “How did we get here?” and “What day is it?” Her partner denies Ms. A has focal neurologic deficits or seizures.

Ms. A had only slept 4 hours the night before she came to the ED because she had just learned that her daughter works in the sex industry. According to her daughter, Ms. A was raped by a soldier many years ago. At that time, her perpetrator told Ms. A that he would kill her entire family if she ever told anyone. As a result, she never pursued any psychological or psychiatric treatment.

During the evaluation, Ms. A shares details regarding her social and medical history; however, she does not recall receiving bad news the night before. She asks the interviewer several times how she got to the hospital, and when a cranial nerve exam is performed, she states, “I am not the patient!”

Ms. A’s vital signs and physical exam are unremarkable. Urinalysis is significant for a ketones level of 20 mmol/L (reference range: negative for ketones), and a urine human chorionic gonadotropin test is negative. A neurologic exam does not identify any focal deficits. No imaging is performed.

Transient global amnesia (TGA) describes an episode of anterograde, and possibly retrograde, amnesia that lasts up to 24 hours. On presentation, patients experiencing TGA repeatedly ask, “Where am I?” “What day is it?” and “How did I get here?” However, semantic memory—such as knowledge of the world and autobiographical information—is preserved.¹ The first case of TGA was described in 1956, and its diagnostic criteria were most recently modified in 1990 (Table²).

Though TGA is the most common cause of acute-onset amnesia, it is rare, affecting approximately 3 to 10 individuals per 100,000. The average age of onset is 61 to 63, with most cases occurring after age 50. TGA is generally thought to affect males and females equally, though some studies suggest a female predominance.³ In most cases (approximately 90%), there is a precipitating event such as physical or emotional stress, change in temperature, or sexual intercourse.⁴

In this article, we provide an overview of the classification, presentation, differential diagnosis, workup, and treatment of TGA. While TGA is a neurologic diagnosis, in a subset of patients it can present with psychiatric features resembling conversion disorder. For such patients, we argue that TGA can be considered a neuropsychiatric condition (Box 1^5-12). This classification may empower emergency psychiatry clinicians and psychotherapists to identify and treat the condition, which is not described by the current psychiatric diagnostic system.

Box 1

Continue to: Differential diagnosis and workup

The differential diagnosis for acute-onset memory loss in the absence of other neurologic or psychiatric features is broad. It includes:

• dissociative amnesia
• ischemic amnesia
• transient epileptic amnesia
• toxic and metabolic amnesia
• posttraumatic amnesia.

Dissociative amnesia (DA), otherwise known as psychogenic amnesia, is “an inability to recall important autobiographical information, usually of a traumatic or stressful nature, that is inconsistent with ordinary forgetting.”¹³ According to this definition, DA features only retro­grade amnesia, as opposed to TGA, which features anterograde amnesia, with possible retrograde amnesia. A subtype of DA—specifically, “continuous amnesia” or “anterograde dissociative amnesia”— is in DSM-5.¹³ However, the diagnostic criteria are unclear, and no cases have been identified in the literature since 1903, before TGA became a diagnostic entity.^5,14 Moreover, patients with DA cannot recall autobiographical information, which is not a feature of TGA. Within DSM-5, TGA is an exclusion criterion for DA.¹³ Thus, an episode of anterograde amnesia with acute onset best meets criteria for TGA, even if there are substantial psychiatric risk factors.

Ischemic amnesia—including stroke and transient ischemic attack (TIA)—is often the primary concern of patients with TGA and their families upon initial presentation, as was the case with Ms. A.^6,15 TIA presenting with isolated, acute-onset amnesia would be highly unusual, because these attacks usually present with focal symptoms including motor deficits, sensory deficits, visual field deficits, and aphasia or dysarthria. A patient with amnesia experiencing a TIA would likely have symptoms lasting from seconds to minutes, which is much shorter than a typical TGA episode.¹⁶

Amnesia secondary to stroke may be transient or permanent.⁷ Amnesia is present in approximately 1% of all strokes and in approximately 19.3% of posterior cerebral artery strokes.^7,17 Unlike TIA and TGA, ischemic amnesia would present with MRI findings detectable at symptom onset. TGA does reveal MRI findings, particularly punctate lesions in the CA1 area of the hippocampus; however, these lesions are typically much smaller than those found in stroke, and are not detectable until 12 to 48 hours after episode onset.^1,17 MRI findings in ischemic amnesia are typically associated with extrahippocampal lesions.¹⁷ Finally, the presence of vascular risk factors such as hyperlipidemia, smoking, diabetes, and hypertension may also favor a diagnosis of stroke or TIA as opposed to TGA, which is not associated with these risk factors.¹⁸ Though ischemic amnesia and TGA usually can be differentiated based on history and presentation, MRI with fluid-attenuated inversion recovery and diffusion-weighted imaging may be performed to definitively distinguish stroke from TGA.⁷

Transient epileptic amnesia (TEA), a focal form of epilepsy within the temporal lobe, should also be considered in patients who present with acute-onset amnesia. Like TGA, TEA may present with simultaneous anterograde and retrograde amnesia accompanied by repetitive questioning.¹⁹ Amnesia can be the sole symptom of TEA in up to 24% of cases. However, several key features distinguish TEA from TGA. TEA most often presents with other clinical signs of seizures, such as oral automatisms and/or olfactory hallucinations.²⁰ There is also a significant difference in episode length; TEA episodes last an average of 30 to 60 minutes and tend to occur upon wakening, whereas TGA episodes last an average of 4 to 6 hours and do not preferentially occur at any particular time.^1,21 In the interictal period—between seizures—patients with TEA may also experience accelerated long-term forgetting, autobiographical amnesia, and topographical amnesia.^19,20 Finally, a diagnosis of TEA also requires recurrent episodes. Recurrence can happen with TGA, but is less frequent.²¹ Generally, history and presentation can distinguish TEA from TGA. Though there is no formal protocol for TEA workup, Lanzone et al²¹ recommend 24-hour EEG or EEG sleep monitoring in patients who present with amnesia as well as other clinical manifestations of epileptic phenomenon.

Continue to: Toxic and metabolic

Toxic and metabolic etiologies of amnesia include opioid and cocaine use, general anesthetics,²² and hypoglycemia.^7,23 Toxic and metabolic causes of amnesia may mirror TGA in their acute onset as well as anterograde nature. However, these patients will likely present with fluctuating consciousness and/or other neuropsychiatric features, such as pressured speech, delusions, and/or distractability.²³ Obtaining a patient’s medical history, including substance use, medication use, and the presence of diabetes,²⁴ is typically sufficient to rule out toxic and metabolic causes.⁷

Posttraumatic amnesia (PTA) describes transient memory loss that occurs after a traumatic brain injury. Anterograde amnesia is most common, though approximately 20% of patients may also experience retro­grade amnesia pertaining to the events near the date of their injury. Unlike TGA, which typically resolves within 24 hours, the recovery time of amnestic symptoms in PTA ranges from minutes to years.⁷ A distinguishing feature of PTA is the presence of confusion, which often resembles a state of delirium.²⁵ The presentation of PTA can vary immensely with regards to agitation, psychotic symptoms, and the time to resolution of the amnesia. Though TGA can be distinguished from PTA based on a lack of clouding of consciousness, a case of anterograde amnesia warrants inquiry into a potential history of head injuries to rule out a traumatic cause.²⁶

Box 2^1,3,23,27-33 outlines current theories of the etiology and pathogenesis of TGA.

Box 2

Transient global ischemia: Psychiatric features

Several studies have demonstrated psychiatric precipitants, features, and comorbidities associated with TGA. Of the TGA cases associated with precipitating events, 29% to 50% are associated with an emotional stressor.^3,4 Examples of emotional stressors include a quarrel,⁴ the announcement of a birth or suicide, and a nightmare.¹⁵ For Ms. A, learning her daughter worked in the sex industry was an emotional stressor.²

During its acute phase, TGA has been shown to present with mood and anxiety symptoms.³⁴ Moreover, during episodes, patients often demonstrate features of panic attacks, such as dizziness, fainting, choking, palpitations, and paresthesia.^3,35

Continue to: Finally, patients with TGA...

Finally, patients with TGA are more likely to have psychiatric comorbidities than those without the condition. In a study of 25 patients who experienced TGA triggered by a precipitant, Inzitari et al⁴ found a strong association of TGA with phobic personality traits, including agoraphobia and simple phobic attitudes (ie, fear of traveling far from home or the sight of blood). Pantoni et al³⁵ replicated these results in 2005 and found that in comparison to patients with TIA, patients with TGA are more likely to have personal and family histories of psychiatric disease. A 2014 study by Dohring et al³⁶ found that compared to healthy controls, patients with TGA are more likely to have maladaptive coping strategies and stress responses. Patients with TGA tended to exhibit increased feelings of guilt, take more medication, and exhibit more anxiety compared to healthy controls.³⁶

Treatment: Benzodiazepines

There are no published treatment guidelines for TGA. However, in case reports, benzodiazepines (specifically lorazepam³⁷) have been shown to have utility in diagnosing and treating DA. The success of benzodiazepines is attributed to its gamma-aminobutyric acid mechanism, which involves inhibiting activity of the N-methyl-D-aspartate (NMDA) receptor, thereby reversing amnesia.³⁷ The NMDA receptor is also implicated in the stress theory of TGA. Though TGA typically resolves on its own within 24 hours, given the distressing nature of this disorder, benzodiazepines may be a suitable option to hasten memory improvement, particularly in patients with psychiatric risk factors.

However, the benzodiazepine midazolam has been identified as a precipitant of TGA. In a case report, Rinehart et al²² identified flumazenil—a benzodiazepine antagonist used primarily to treat retrograde postoperative amnesia—as an antidote. The potentially paradoxical role of benzodiazepines in both the precipitation and treatment of TGA may relate back to the heterogeneity of the etiologies of TGA. Further research comparing the treatment of TGA in patients with stress-induced TGA vs postoperative TGA is needed to better understand the neurochemical basis of TGA and work toward establishing optimal treatment options for different patient demographics.

A generally favorable prognosis

TGA carries a low risk of recurrence. In studies with 3- to 7-year follow-up periods, the recurrence rates ranged from 1.4% to 23.8%.^23,35,38

Memory impairments may be present for 5 to 6 months following a TGA episode. The severity of these impairments may range from clinically unnoticeable to the patient meeting the criteria for mild cognitive impairment.^23,39 The risk is higher in patients who have had recurrent TGA compared to those patients who have experienced only a single episode.²³

Continue to: TGA does not increase...

TGA does not increase the risk of cerebrovascular events. There is controversy regarding a potentially increased risk for dementia as well as epilepsy, though there is insufficient evidence to support these findings.^23,40

CASE CONTINUED

Five hours after the onset of Ms. A’s symptoms, the treatment team initiates oral lorazepam 1 mg. One hour after taking lorazepam, Ms. A’s anterograde and retrograde amnesia improve. She cannot recall why she was brought to the hospital but does remember the date and location, which she was not able to do on initial presentation. She feels safe, states a clear plan for self-care, and is discharged in the care of her partner. Though Ms. A’s memory improved soon after she received lorazepam, this improvement also could be attributed to the natural course of time, as TGA tends to resolve on its own within 24 hours.

Bottom Line

Transient global amnesia (TGA) is an episode of anterograde, and possibly retrograde, amnesia that lasts up to 24 hours. It represents an interesting diagnosis at the intersection of psychiatry and neurology. TGA has many established psychiatric risk factors and features—some of which may resemble conversion disorder—but these may only apply to a particular subset of patients, which reflects the heterogeneity of the condition.

Related Resources

• Sparaco M, Pascarella R, Muccio CF, et al. Forgetting the unforgettable: transient global amnesia part I: pathophysiology and etiology. J Clin Med. 2022;11(12): 3373. doi:10.3390/jcm1112337
• Sparaco M, Pascarella R, Muccio CF, et al. Forgetting the unforgettable: transient global amnesia part II: a clinical road map. J Clin Med. 2022;11(14):3940. doi:10.3390/ jcm11143940

Drug Brand Names

Flumazenil • Romazicon
Lorazepam • Ativan
Midazolam • Versed

Ms. A, age 48, is a physician’s assistant with no psychiatric history. She presents to the emergency department (ED) with her partner and daughter due to a 15-minute episode of acute-onset memory loss and concern for stroke. In the ED, Ms. A is confused and repeatedly asks, “Where are we?” “How did we get here?” and “What day is it?” Her partner denies Ms. A has focal neurologic deficits or seizures.

Ms. A had only slept 4 hours the night before she came to the ED because she had just learned that her daughter works in the sex industry. According to her daughter, Ms. A was raped by a soldier many years ago. At that time, her perpetrator told Ms. A that he would kill her entire family if she ever told anyone. As a result, she never pursued any psychological or psychiatric treatment.

During the evaluation, Ms. A shares details regarding her social and medical history; however, she does not recall receiving bad news the night before. She asks the interviewer several times how she got to the hospital, and when a cranial nerve exam is performed, she states, “I am not the patient!”

Ms. A’s vital signs and physical exam are unremarkable. Urinalysis is significant for a ketones level of 20 mmol/L (reference range: negative for ketones), and a urine human chorionic gonadotropin test is negative. A neurologic exam does not identify any focal deficits. No imaging is performed.

Transient global amnesia (TGA) describes an episode of anterograde, and possibly retrograde, amnesia that lasts up to 24 hours. On presentation, patients experiencing TGA repeatedly ask, “Where am I?” “What day is it?” and “How did I get here?” However, semantic memory—such as knowledge of the world and autobiographical information—is preserved.¹ The first case of TGA was described in 1956, and its diagnostic criteria were most recently modified in 1990 (Table²).

Though TGA is the most common cause of acute-onset amnesia, it is rare, affecting approximately 3 to 10 individuals per 100,000. The average age of onset is 61 to 63, with most cases occurring after age 50. TGA is generally thought to affect males and females equally, though some studies suggest a female predominance.³ In most cases (approximately 90%), there is a precipitating event such as physical or emotional stress, change in temperature, or sexual intercourse.⁴

In this article, we provide an overview of the classification, presentation, differential diagnosis, workup, and treatment of TGA. While TGA is a neurologic diagnosis, in a subset of patients it can present with psychiatric features resembling conversion disorder. For such patients, we argue that TGA can be considered a neuropsychiatric condition (Box 1^5-12). This classification may empower emergency psychiatry clinicians and psychotherapists to identify and treat the condition, which is not described by the current psychiatric diagnostic system.

Box 1

Continue to: Differential diagnosis and workup

The differential diagnosis for acute-onset memory loss in the absence of other neurologic or psychiatric features is broad. It includes:

• dissociative amnesia
• ischemic amnesia
• transient epileptic amnesia
• toxic and metabolic amnesia
• posttraumatic amnesia.

Dissociative amnesia (DA), otherwise known as psychogenic amnesia, is “an inability to recall important autobiographical information, usually of a traumatic or stressful nature, that is inconsistent with ordinary forgetting.”¹³ According to this definition, DA features only retro­grade amnesia, as opposed to TGA, which features anterograde amnesia, with possible retrograde amnesia. A subtype of DA—specifically, “continuous amnesia” or “anterograde dissociative amnesia”— is in DSM-5.¹³ However, the diagnostic criteria are unclear, and no cases have been identified in the literature since 1903, before TGA became a diagnostic entity.^5,14 Moreover, patients with DA cannot recall autobiographical information, which is not a feature of TGA. Within DSM-5, TGA is an exclusion criterion for DA.¹³ Thus, an episode of anterograde amnesia with acute onset best meets criteria for TGA, even if there are substantial psychiatric risk factors.

Ischemic amnesia—including stroke and transient ischemic attack (TIA)—is often the primary concern of patients with TGA and their families upon initial presentation, as was the case with Ms. A.^6,15 TIA presenting with isolated, acute-onset amnesia would be highly unusual, because these attacks usually present with focal symptoms including motor deficits, sensory deficits, visual field deficits, and aphasia or dysarthria. A patient with amnesia experiencing a TIA would likely have symptoms lasting from seconds to minutes, which is much shorter than a typical TGA episode.¹⁶

Amnesia secondary to stroke may be transient or permanent.⁷ Amnesia is present in approximately 1% of all strokes and in approximately 19.3% of posterior cerebral artery strokes.^7,17 Unlike TIA and TGA, ischemic amnesia would present with MRI findings detectable at symptom onset. TGA does reveal MRI findings, particularly punctate lesions in the CA1 area of the hippocampus; however, these lesions are typically much smaller than those found in stroke, and are not detectable until 12 to 48 hours after episode onset.^1,17 MRI findings in ischemic amnesia are typically associated with extrahippocampal lesions.¹⁷ Finally, the presence of vascular risk factors such as hyperlipidemia, smoking, diabetes, and hypertension may also favor a diagnosis of stroke or TIA as opposed to TGA, which is not associated with these risk factors.¹⁸ Though ischemic amnesia and TGA usually can be differentiated based on history and presentation, MRI with fluid-attenuated inversion recovery and diffusion-weighted imaging may be performed to definitively distinguish stroke from TGA.⁷

Transient epileptic amnesia (TEA), a focal form of epilepsy within the temporal lobe, should also be considered in patients who present with acute-onset amnesia. Like TGA, TEA may present with simultaneous anterograde and retrograde amnesia accompanied by repetitive questioning.¹⁹ Amnesia can be the sole symptom of TEA in up to 24% of cases. However, several key features distinguish TEA from TGA. TEA most often presents with other clinical signs of seizures, such as oral automatisms and/or olfactory hallucinations.²⁰ There is also a significant difference in episode length; TEA episodes last an average of 30 to 60 minutes and tend to occur upon wakening, whereas TGA episodes last an average of 4 to 6 hours and do not preferentially occur at any particular time.^1,21 In the interictal period—between seizures—patients with TEA may also experience accelerated long-term forgetting, autobiographical amnesia, and topographical amnesia.^19,20 Finally, a diagnosis of TEA also requires recurrent episodes. Recurrence can happen with TGA, but is less frequent.²¹ Generally, history and presentation can distinguish TEA from TGA. Though there is no formal protocol for TEA workup, Lanzone et al²¹ recommend 24-hour EEG or EEG sleep monitoring in patients who present with amnesia as well as other clinical manifestations of epileptic phenomenon.

Continue to: Toxic and metabolic

Toxic and metabolic etiologies of amnesia include opioid and cocaine use, general anesthetics,²² and hypoglycemia.^7,23 Toxic and metabolic causes of amnesia may mirror TGA in their acute onset as well as anterograde nature. However, these patients will likely present with fluctuating consciousness and/or other neuropsychiatric features, such as pressured speech, delusions, and/or distractability.²³ Obtaining a patient’s medical history, including substance use, medication use, and the presence of diabetes,²⁴ is typically sufficient to rule out toxic and metabolic causes.⁷

Posttraumatic amnesia (PTA) describes transient memory loss that occurs after a traumatic brain injury. Anterograde amnesia is most common, though approximately 20% of patients may also experience retro­grade amnesia pertaining to the events near the date of their injury. Unlike TGA, which typically resolves within 24 hours, the recovery time of amnestic symptoms in PTA ranges from minutes to years.⁷ A distinguishing feature of PTA is the presence of confusion, which often resembles a state of delirium.²⁵ The presentation of PTA can vary immensely with regards to agitation, psychotic symptoms, and the time to resolution of the amnesia. Though TGA can be distinguished from PTA based on a lack of clouding of consciousness, a case of anterograde amnesia warrants inquiry into a potential history of head injuries to rule out a traumatic cause.²⁶

Box 2^1,3,23,27-33 outlines current theories of the etiology and pathogenesis of TGA.

Box 2

Transient global ischemia: Psychiatric features

Several studies have demonstrated psychiatric precipitants, features, and comorbidities associated with TGA. Of the TGA cases associated with precipitating events, 29% to 50% are associated with an emotional stressor.^3,4 Examples of emotional stressors include a quarrel,⁴ the announcement of a birth or suicide, and a nightmare.¹⁵ For Ms. A, learning her daughter worked in the sex industry was an emotional stressor.²

During its acute phase, TGA has been shown to present with mood and anxiety symptoms.³⁴ Moreover, during episodes, patients often demonstrate features of panic attacks, such as dizziness, fainting, choking, palpitations, and paresthesia.^3,35

Continue to: Finally, patients with TGA...

Finally, patients with TGA are more likely to have psychiatric comorbidities than those without the condition. In a study of 25 patients who experienced TGA triggered by a precipitant, Inzitari et al⁴ found a strong association of TGA with phobic personality traits, including agoraphobia and simple phobic attitudes (ie, fear of traveling far from home or the sight of blood). Pantoni et al³⁵ replicated these results in 2005 and found that in comparison to patients with TIA, patients with TGA are more likely to have personal and family histories of psychiatric disease. A 2014 study by Dohring et al³⁶ found that compared to healthy controls, patients with TGA are more likely to have maladaptive coping strategies and stress responses. Patients with TGA tended to exhibit increased feelings of guilt, take more medication, and exhibit more anxiety compared to healthy controls.³⁶

Treatment: Benzodiazepines

There are no published treatment guidelines for TGA. However, in case reports, benzodiazepines (specifically lorazepam³⁷) have been shown to have utility in diagnosing and treating DA. The success of benzodiazepines is attributed to its gamma-aminobutyric acid mechanism, which involves inhibiting activity of the N-methyl-D-aspartate (NMDA) receptor, thereby reversing amnesia.³⁷ The NMDA receptor is also implicated in the stress theory of TGA. Though TGA typically resolves on its own within 24 hours, given the distressing nature of this disorder, benzodiazepines may be a suitable option to hasten memory improvement, particularly in patients with psychiatric risk factors.

However, the benzodiazepine midazolam has been identified as a precipitant of TGA. In a case report, Rinehart et al²² identified flumazenil—a benzodiazepine antagonist used primarily to treat retrograde postoperative amnesia—as an antidote. The potentially paradoxical role of benzodiazepines in both the precipitation and treatment of TGA may relate back to the heterogeneity of the etiologies of TGA. Further research comparing the treatment of TGA in patients with stress-induced TGA vs postoperative TGA is needed to better understand the neurochemical basis of TGA and work toward establishing optimal treatment options for different patient demographics.

A generally favorable prognosis

TGA carries a low risk of recurrence. In studies with 3- to 7-year follow-up periods, the recurrence rates ranged from 1.4% to 23.8%.^23,35,38

Memory impairments may be present for 5 to 6 months following a TGA episode. The severity of these impairments may range from clinically unnoticeable to the patient meeting the criteria for mild cognitive impairment.^23,39 The risk is higher in patients who have had recurrent TGA compared to those patients who have experienced only a single episode.²³

Continue to: TGA does not increase...

TGA does not increase the risk of cerebrovascular events. There is controversy regarding a potentially increased risk for dementia as well as epilepsy, though there is insufficient evidence to support these findings.^23,40

CASE CONTINUED

Five hours after the onset of Ms. A’s symptoms, the treatment team initiates oral lorazepam 1 mg. One hour after taking lorazepam, Ms. A’s anterograde and retrograde amnesia improve. She cannot recall why she was brought to the hospital but does remember the date and location, which she was not able to do on initial presentation. She feels safe, states a clear plan for self-care, and is discharged in the care of her partner. Though Ms. A’s memory improved soon after she received lorazepam, this improvement also could be attributed to the natural course of time, as TGA tends to resolve on its own within 24 hours.

Bottom Line

Transient global amnesia (TGA) is an episode of anterograde, and possibly retrograde, amnesia that lasts up to 24 hours. It represents an interesting diagnosis at the intersection of psychiatry and neurology. TGA has many established psychiatric risk factors and features—some of which may resemble conversion disorder—but these may only apply to a particular subset of patients, which reflects the heterogeneity of the condition.

Related Resources

• Sparaco M, Pascarella R, Muccio CF, et al. Forgetting the unforgettable: transient global amnesia part I: pathophysiology and etiology. J Clin Med. 2022;11(12): 3373. doi:10.3390/jcm1112337
• Sparaco M, Pascarella R, Muccio CF, et al. Forgetting the unforgettable: transient global amnesia part II: a clinical road map. J Clin Med. 2022;11(14):3940. doi:10.3390/ jcm11143940

Drug Brand Names

Flumazenil • Romazicon
Lorazepam • Ativan
Midazolam • Versed

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Increasing intake of folate and vitamin B6 beyond recommended daily levels offers no protective benefit against Parkinson’s disease (PD), a new study shows.

Though there was some evidence that vitamin B12 early in life was associated with decreased PD risk, the findings were inconsistent and were observed only in people whose daily intake was 10 times the recommended level.

“The results of this large prospective study do not support the hypothesis that increasing folate or vitamin B6 intakes above the current levels would reduce PD risk in this population of mostly White U.S. health professionals,” lead investigator Mario H. Flores-Torres, MD, PhD, a research scientist in the department of nutrition at the Harvard T.H. Chan School of Public Health, Boston, said in an interview.

However, he added, the study “leaves open the possibility that in some individuals the intake of vitamin B12 contributes to PD risk – a finding that warrants further research.”

The findings were published online  in Movement Disorders.
 

Mixed findings

Previous studies have suggested B vitamins – including folate, B6 and B12 – might affect PD risk, but results have been mixed.

The new study included 80,965 women from the Nurses’ Health Study (1984-2016) and 48,837 men from the Health Professionals Follow-up Study (1986-2016). The average age at baseline was 50 years in women and 54 years in men, and participants were followed for about 30 years.

Participants completed questionnaires about diet at the beginning of the study and again every 4 years.

To account for the possibility of reverse causation due to the long prodromal phase of PD, investigators conducted lagged analyses at 8, 12, 16, and 20 years.

During the follow-up period, 1,426 incident cases of PD were diagnosed (687 in women and 739 in men).

Researchers found no link between reduced PD risk and intake of vitamin B6 or folate.

Though the total cumulative average intake of vitamin B12 was not associated with PD risk, investigators noted a modest decrease in risk between those with highest baseline of B12 and participants with the lowest baseline levels (hazard ratio, 0.80; P = .01).

Individuals in the highest quintile of B12 intake at baseline had an average intake of 21-22 mcg/d, close to 10 times the recommended daily intake of 2.4 mcg/d.

“Although some of our results suggest that a higher intake of vitamin B12 may decrease the risk of PD in a population of U.S. health professionals, the associations we observed were modest and not entirely consistent,” Dr. Flores-Torres said.

“Additional studies need to confirm our findings to better understand whether people who take higher amounts of B12 younger in life may have a protective benefit against PD,” he added.
 

The whole picture?

Commenting on the findings for this article, Rebecca Gilbert, MD, PhD, chief scientific officer of the American Parkinson Disease Association, New York, noted that checking B vitamin levels is a fairly standard practice for most clinicians. In that regard, this study highlights why this is important.

“Neurologists will often test B12 levels and recommend a supplement if your level is below the normal range,” she said. “No one is questioning the value of B12 for nerves and recommend that B12 is in the normal to high normal range.”

But understanding how B vitamins may or may not affect PD risk might require a different kind of study.

“This analysis, much like many others, is trying so hard to figure out what is it in diets that affects Parkinson’s disease risk,” Dr. Gilbert said. “But we have yet to say these are the nutrients that prevent Parkinson’s or increase the risk.”

One reason for the conflicting results in studies such as this could be that the explanation for the link between diet and PD risk may not be in specific minerals consumed but rather in the diet as a whole.

“Focusing on specific elements of a diet may not give us the answer,” Dr. Gilbert said. “We should be analyzing diet as a complete holistic picture because it’s not just the elements but how everything in what we eat works together.”

The study was funded by the National Institutes of Health and the Parkinson’s Foundation. Dr. Flores-Torres and Dr. Gilbert report no relevant conflicts.
 

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Imaging tests may miss early signs of multiple sclerosis (MS) in children who have no symptoms of the disease, according to a recent study that points to the need for a change in diagnostic criteria for the neuromuscular condition.

The findings suggest that children, unlike adults, may not need to meet the current clinical standard criteria to be considered at risk for MS.

“This is an important study confirming that some children who have no symptoms of demyelinating disease may nonetheless have MRI findings suggestive of demyelination detected on brain imaging,” said Naila Makhani, MD, associate professor of pediatrics and of neurology at Yale University and director of the Yale Pediatric Neuroimmunology Program, New Haven, Conn. Dr. Makhani was not affiliated with the study.

Researchers reviewed the MRI scans of 38 children aged 7-17 years who had radiologically isolated syndrome (RIS), a possible precursor to MS.

Like MS, RIS is characterized by destruction of the myelin. However, RIS is generally asymptomatic.

While RIS has been linked to MS, a diagnosis of RIS does not mean someone will be diagnosed with MS. Previous studies have shown that at least 3% of MS cases begin before age 16.

The children in the study likely received an MRI because of complaints of headaches or after having been diagnosed with a concussion, according to the researchers. The participants also did not show physical symptoms for MS, nor did they meet the McDonald or Barkohf criteria, which are clinical standards used to diagnose the condition in adults and children.

Within an average of 3 years following the imaging and RIS diagnosis, almost 36% of the children experienced a clinical attack, which led to an MS diagnosis. Almost three-fourths of the children developed additional brain and spinal cord lesions in the myelin that were evident on MRI.

MS often is diagnosed after a patient has had a clinical attack, such as vision impairment, loss of balance, inflammation, or severe fatigue. Identifying the potential for the disease earlier may allow clinicians to treat sooner, according to Leslie Benson, MD, assistant director of pediatric neuroimmunology at Massachusetts General Hospital, Boston, and one of the study authors.

“The field is leaning toward [the question of], ‘Should we treat presymptomatic MS?’ ” said Dr. Benson. “If we have the opportunity to prevent disability and improve long-term outcomes with safe medications, then we would like to do so.”

The findings were published in the journal Multiple Sclerosis and Related Disorders.

According to Dr. Benson and her colleagues, adjustments to the McDonald or Barkohf criteria for children may help in the detection of RIS and may allow earlier identification of MS.

“We don’t really know when MS first starts,” Dr. Benson said. “Unless you happen to have an MRI or symptoms, there’s no way to know how long the lesions have been evolving and how long the disease progression that led to those lesions has been there.”

MRI images showing lesions in the brain stem and spinal cord of children appeared to be different from those typically seen in adults, according to Tanuja Chitnis, MD, director of the Mass General Brigham Pediatric MS Center in Boston, who is one of the study’s coauthors.

“The concern of many practitioners is whether we should be treating at the first sign of MS,” Dr. Chitnis said. “We need to understand it better in children, and in teenagers especially, when these probably start biologically.”

Dr. Benson said current criteria for diagnosing MS in children require meeting a high threshold, which may limit diagnoses to those whose condition has progressed.

“This may miss patients at risk for MS,” Dr. Benson said. “That idea of who do you diagnose RIS and what criteria work to accurately diagnose RIS is really important.”

For now, the challenge remains of investigating characteristics of patients with RIS who will later have a clinical attack.

“We need a better understanding of what criteria do need to be met and how we can best risk-stratify our patients,” Dr. Benson said. “If it is recommended to treat presymptomatic cases, that we can best stratify those at risk and not overtreat those not at risk.”

Dr. Makhani receives funding from the National Institutes of Health, the Charles H. Hood Foundation, and the Multiple Sclerosis Society.

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

Physical exercise may improve the motor symptoms and quality of life for patients with Parkinson’s disease, new research shows. A systematic review of 156 clinical trials involving 8,000 patients with Parkinson’s disease showed dancing and aquatic exercise, in particular, were most likely to improve motor symptoms, while swimming, endurance training, and mind-body training were most likely to benefit quality of life.

“For most types of exercise we studied, we observed positive effects on both the severity of motor signs and quality of life. These results highlight the importance of exercise in general, as they suggest people with Parkinson’s disease can benefit from a variety of exercises,” said study investigator Moritz Ernst, MSc, deputy head of the working group on evidence-based medicine at the University Hospital Cologne (Germany).

University Hospital Cologne

“Clinicians and people with Parkinson’s disease may have several options of exercise programs to choose from when establishing an individual training routine,” he added, emphasizing that overall those with Parkinson’s disease should seek professional advice, including assessment of motor and nonmotor symptoms, to develop a training agenda based on their individual needs.

The study was published online in the Cochrane Database of Systematic Reviews.
 

May I have this dance?

The investigators analyzed data from randomized, controlled trials comparing different types of exercise and no exercise and the subsequent effect on Parkinson’s disease symptoms. Exercise included dance, strength-resistance training, mind-body training such as tai chi and yoga, water-based training, resistance training, gait/balance/functional training, and endurance training.

The average age of study participants ranged from 60 to 74 years, and most of the studies included patients with mild to moderate Parkinson’s disease. The mean length of the various interventions was 12 weeks.

When the researchers examined the effect of exercise on motor symptoms, they found that dance (P = .88), aqua-based training (P = .69), and gait/balance/functional training (P = .67) were most likely to reduce symptom severity.

Aqua-based training (P = .95), endurance training (P = .77), and mind-body training (P = .75) were most were most likely to benefit quality of life, although the investigators caution that these findings were at risk of bias because quality of life was self-reported.

The investigators noted other study limitations including the fact that most of the studies included in the review had small sample sizes and their study only included patients with mild to moderate versus severe Parkinson’s disease.

The authors said that future research should include larger samples, report intent-to-treat analyses, and involve participants with more advanced forms of Parkinson’s disease who may also have cognitive difficulties.
 

Prescribe exercise

“We should be giving our patients, no matter where they are in their disease stage, a ‘prescription’ to exercise,” said Mitra Afshari, MD, MPH. Dr. Afshari was not involved in the study but leads her own research on Parkinson’s disease and exercise as the site principal investigator on the National Institutes of Health–funded SPARX3 Study in Parkinson’s Disease and Exercise at Rush University in Chicago. She said that, based on her experience caring for patients with Parkinson’s disease at all disease stages, “patients who have been physically active their whole lives and can maintain that activity despite their diagnosis fare the best.”

However, she added, those who initiate physical exercise after diagnosis can also do very well and reap benefits, including improved motor symptoms.

The study was funded by University Hospital of Cologne, Faculty of Medicine and University Hospital, University of Cologne, and the German Ministry of Education and Research. The authors have disclosed no relevant financial relationships.

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

Physical exercise may improve the motor symptoms and quality of life for patients with Parkinson’s disease, new research shows. A systematic review of 156 clinical trials involving 8,000 patients with Parkinson’s disease showed dancing and aquatic exercise, in particular, were most likely to improve motor symptoms, while swimming, endurance training, and mind-body training were most likely to benefit quality of life.

“For most types of exercise we studied, we observed positive effects on both the severity of motor signs and quality of life. These results highlight the importance of exercise in general, as they suggest people with Parkinson’s disease can benefit from a variety of exercises,” said study investigator Moritz Ernst, MSc, deputy head of the working group on evidence-based medicine at the University Hospital Cologne (Germany).

University Hospital Cologne

“Clinicians and people with Parkinson’s disease may have several options of exercise programs to choose from when establishing an individual training routine,” he added, emphasizing that overall those with Parkinson’s disease should seek professional advice, including assessment of motor and nonmotor symptoms, to develop a training agenda based on their individual needs.

The study was published online in the Cochrane Database of Systematic Reviews.
 

May I have this dance?

The investigators analyzed data from randomized, controlled trials comparing different types of exercise and no exercise and the subsequent effect on Parkinson’s disease symptoms. Exercise included dance, strength-resistance training, mind-body training such as tai chi and yoga, water-based training, resistance training, gait/balance/functional training, and endurance training.

The average age of study participants ranged from 60 to 74 years, and most of the studies included patients with mild to moderate Parkinson’s disease. The mean length of the various interventions was 12 weeks.

When the researchers examined the effect of exercise on motor symptoms, they found that dance (P = .88), aqua-based training (P = .69), and gait/balance/functional training (P = .67) were most likely to reduce symptom severity.

Aqua-based training (P = .95), endurance training (P = .77), and mind-body training (P = .75) were most were most likely to benefit quality of life, although the investigators caution that these findings were at risk of bias because quality of life was self-reported.

The investigators noted other study limitations including the fact that most of the studies included in the review had small sample sizes and their study only included patients with mild to moderate versus severe Parkinson’s disease.

The authors said that future research should include larger samples, report intent-to-treat analyses, and involve participants with more advanced forms of Parkinson’s disease who may also have cognitive difficulties.
 

Prescribe exercise

“We should be giving our patients, no matter where they are in their disease stage, a ‘prescription’ to exercise,” said Mitra Afshari, MD, MPH. Dr. Afshari was not involved in the study but leads her own research on Parkinson’s disease and exercise as the site principal investigator on the National Institutes of Health–funded SPARX3 Study in Parkinson’s Disease and Exercise at Rush University in Chicago. She said that, based on her experience caring for patients with Parkinson’s disease at all disease stages, “patients who have been physically active their whole lives and can maintain that activity despite their diagnosis fare the best.”

However, she added, those who initiate physical exercise after diagnosis can also do very well and reap benefits, including improved motor symptoms.

The study was funded by University Hospital of Cologne, Faculty of Medicine and University Hospital, University of Cologne, and the German Ministry of Education and Research. The authors have disclosed no relevant financial relationships.

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

Physical exercise may improve the motor symptoms and quality of life for patients with Parkinson’s disease, new research shows. A systematic review of 156 clinical trials involving 8,000 patients with Parkinson’s disease showed dancing and aquatic exercise, in particular, were most likely to improve motor symptoms, while swimming, endurance training, and mind-body training were most likely to benefit quality of life.

“For most types of exercise we studied, we observed positive effects on both the severity of motor signs and quality of life. These results highlight the importance of exercise in general, as they suggest people with Parkinson’s disease can benefit from a variety of exercises,” said study investigator Moritz Ernst, MSc, deputy head of the working group on evidence-based medicine at the University Hospital Cologne (Germany).

University Hospital Cologne

“Clinicians and people with Parkinson’s disease may have several options of exercise programs to choose from when establishing an individual training routine,” he added, emphasizing that overall those with Parkinson’s disease should seek professional advice, including assessment of motor and nonmotor symptoms, to develop a training agenda based on their individual needs.

The study was published online in the Cochrane Database of Systematic Reviews.
 

May I have this dance?

The investigators analyzed data from randomized, controlled trials comparing different types of exercise and no exercise and the subsequent effect on Parkinson’s disease symptoms. Exercise included dance, strength-resistance training, mind-body training such as tai chi and yoga, water-based training, resistance training, gait/balance/functional training, and endurance training.

The average age of study participants ranged from 60 to 74 years, and most of the studies included patients with mild to moderate Parkinson’s disease. The mean length of the various interventions was 12 weeks.

When the researchers examined the effect of exercise on motor symptoms, they found that dance (P = .88), aqua-based training (P = .69), and gait/balance/functional training (P = .67) were most likely to reduce symptom severity.

Aqua-based training (P = .95), endurance training (P = .77), and mind-body training (P = .75) were most were most likely to benefit quality of life, although the investigators caution that these findings were at risk of bias because quality of life was self-reported.

The investigators noted other study limitations including the fact that most of the studies included in the review had small sample sizes and their study only included patients with mild to moderate versus severe Parkinson’s disease.

The authors said that future research should include larger samples, report intent-to-treat analyses, and involve participants with more advanced forms of Parkinson’s disease who may also have cognitive difficulties.
 

Prescribe exercise

“We should be giving our patients, no matter where they are in their disease stage, a ‘prescription’ to exercise,” said Mitra Afshari, MD, MPH. Dr. Afshari was not involved in the study but leads her own research on Parkinson’s disease and exercise as the site principal investigator on the National Institutes of Health–funded SPARX3 Study in Parkinson’s Disease and Exercise at Rush University in Chicago. She said that, based on her experience caring for patients with Parkinson’s disease at all disease stages, “patients who have been physically active their whole lives and can maintain that activity despite their diagnosis fare the best.”

However, she added, those who initiate physical exercise after diagnosis can also do very well and reap benefits, including improved motor symptoms.

The study was funded by University Hospital of Cologne, Faculty of Medicine and University Hospital, University of Cologne, and the German Ministry of Education and Research. The authors have disclosed no relevant financial relationships.

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