Neurology Reviews

Certain reproductive factors are associated with greater or lower risk of dementia, according to researchers who conducted a large population-based study with UK Biobank data.

Jessica Gong, a PhD candidate at the George Institute for Global Health at University of New South Wales in Australia, and coauthors found a greater dementia risk in women with early and late menarche, women who were younger when they first gave birth, and those who had had a hysterectomy, especially those who had a hysterectomy without concomitant oophorectomy or with a previous oophorectomy.

After controlling for key confounders, the researchers found lower risk of all-cause dementia if women had ever been pregnant, ever had an abortion, had a longer reproductive span, or had later menopause.

Use of oral contraceptive pills was associated with a lower dementia risk, they found.

In this study, there was no evidence that hormone therapy (HT) was associated with dementia risk (hazard ratio, 0.99, 95% confidence interval [0.90-1.09], P =.0828).

The analysis, published online April 5 in PLOS Medicine, comprised 273,240 women and 228,957 men without prevalent dementia.

The authors noted that dementia rates are increasing. Globally, 50 million people live with dementia, and the number is expected to triple by 2050, according to Alzheimer’s Disease International.

“Our study identified certain reproductive factors related to shorter exposure to endogenous estrogen were associated with increased risk of dementia, highlighting the susceptibility in dementia risk pertaining to women,” Ms. Gong told this publication.
 

Risk comparison of men and women

Men were included in this study to compare the association between number of children fathered and the risk of all-cause dementia, with the association in their female counterparts.

The U-shaped associations between the number of children and dementia risk were similar for both sexes, suggesting that the risk difference in women may not be associated with factors associated with childbearing

“It may be more related to social and behavioral factors in parenthood, rather than biological factors involved in childbearing,” Ms. Gong said.

Compared with those with two children, for those without children, the multiple adjusted HR (95% CI) was 1.18 (1.04, 1.33) (P = .027) for women and 1.10 (0.98-1.23) P = .164) for men.

For those with four or more children, the HR was 1.14 (0.98, 1.33) (P = .132) for women and 1.26 (1.10-1.45) (P = .003) for men.

Rachel Buckley, PhD, assistant professor of neurology with a dual appointment at Brigham and Women’s and Massachusetts General hospitals in Boston, told this publication she found the comparison of dementia risk with number of children in men and women “fascinating.”

She said the argument usually is that if women have had more births, then they have had more estrogen through their body because women get a huge injection of hormones in pregnancy.

“The idea is that the more pregnancies you have the more protected you are. But this study put that on its head, because if men and women are showing increased [dementia] risk in the number of children they have, it suggests there must be something about having the children – not necessarily the circulating hormones – that might be having an impact,” Dr. Buckley said.

“I had never thought to compare the number of children in men. I do find that very interesting,” she said.

As for the lack of a link between HT and dementia risk, in this study she said, she wouldn’t shut the door on that discussion just yet.

She noted the long history of controversy in the field about whether there is a protective factor against dementia for estrogen or whether exposure to estrogen leads to increased risk.

Before the landmark Women’s Health Initiative (WHI) study in the 1990s, she pointed out, there was evidence in many observational studies that women who had longer exposure to estrogen – whether that was earlier age at first period and later age at menopause combined or women had taken hormone therapy at some point, had less risk for dementia.

Dr. Buckley said that in a secondary outcome of WHI, however, “there was increased risk for progression to dementia in women who were taking hormone therapy which essentially flipped the field on its ahead because until that point everybody thought that estrogen was a protective factor.”

She said although this study found no association with dementia, she still thinks HT has a role to play and that it may just need to be better tailored to individuals.

“If you think about it, we have our tailored cocktail of hormones in our body and who’s to say that my hormones are going to be the same as yours? Why should you and I be put on the same hormone therapy and assume that will give us the same outcome? I think we could do a lot better with customization and calibration of hormones to aid in women’s health.”
 

Lifetime approach to dementia

Ms. Gong says future dementia risk-reduction strategies should consider sex-specific risk, and consider the reproductive events that took place in women’s lifespans as well as their entire hormone history when assessing dementia risk, to ensure that the strategies are sex sensitive.

Dr. Buckley agrees: “I don’t think we should ever think about dementia in terms of 65 onwards. We know this disease is insidious and it starts very, very early.”

Regarding limitations, the authors noted that it was a retrospective study that included self-reported measures of reproductive factors, which may be inherently subject to recall bias.

A coauthor does consultant work for Amgen, Freeline, and Kirin outside the submitted work. There were no other relevant financial disclosures.

Certain reproductive factors are associated with greater or lower risk of dementia, according to researchers who conducted a large population-based study with UK Biobank data.

Jessica Gong, a PhD candidate at the George Institute for Global Health at University of New South Wales in Australia, and coauthors found a greater dementia risk in women with early and late menarche, women who were younger when they first gave birth, and those who had had a hysterectomy, especially those who had a hysterectomy without concomitant oophorectomy or with a previous oophorectomy.

After controlling for key confounders, the researchers found lower risk of all-cause dementia if women had ever been pregnant, ever had an abortion, had a longer reproductive span, or had later menopause.

Use of oral contraceptive pills was associated with a lower dementia risk, they found.

In this study, there was no evidence that hormone therapy (HT) was associated with dementia risk (hazard ratio, 0.99, 95% confidence interval [0.90-1.09], P =.0828).

The analysis, published online April 5 in PLOS Medicine, comprised 273,240 women and 228,957 men without prevalent dementia.

The authors noted that dementia rates are increasing. Globally, 50 million people live with dementia, and the number is expected to triple by 2050, according to Alzheimer’s Disease International.

“Our study identified certain reproductive factors related to shorter exposure to endogenous estrogen were associated with increased risk of dementia, highlighting the susceptibility in dementia risk pertaining to women,” Ms. Gong told this publication.
 

Risk comparison of men and women

Men were included in this study to compare the association between number of children fathered and the risk of all-cause dementia, with the association in their female counterparts.

The U-shaped associations between the number of children and dementia risk were similar for both sexes, suggesting that the risk difference in women may not be associated with factors associated with childbearing

“It may be more related to social and behavioral factors in parenthood, rather than biological factors involved in childbearing,” Ms. Gong said.

Compared with those with two children, for those without children, the multiple adjusted HR (95% CI) was 1.18 (1.04, 1.33) (P = .027) for women and 1.10 (0.98-1.23) P = .164) for men.

For those with four or more children, the HR was 1.14 (0.98, 1.33) (P = .132) for women and 1.26 (1.10-1.45) (P = .003) for men.

Rachel Buckley, PhD, assistant professor of neurology with a dual appointment at Brigham and Women’s and Massachusetts General hospitals in Boston, told this publication she found the comparison of dementia risk with number of children in men and women “fascinating.”

She said the argument usually is that if women have had more births, then they have had more estrogen through their body because women get a huge injection of hormones in pregnancy.

“The idea is that the more pregnancies you have the more protected you are. But this study put that on its head, because if men and women are showing increased [dementia] risk in the number of children they have, it suggests there must be something about having the children – not necessarily the circulating hormones – that might be having an impact,” Dr. Buckley said.

“I had never thought to compare the number of children in men. I do find that very interesting,” she said.

As for the lack of a link between HT and dementia risk, in this study she said, she wouldn’t shut the door on that discussion just yet.

She noted the long history of controversy in the field about whether there is a protective factor against dementia for estrogen or whether exposure to estrogen leads to increased risk.

Before the landmark Women’s Health Initiative (WHI) study in the 1990s, she pointed out, there was evidence in many observational studies that women who had longer exposure to estrogen – whether that was earlier age at first period and later age at menopause combined or women had taken hormone therapy at some point, had less risk for dementia.

Dr. Buckley said that in a secondary outcome of WHI, however, “there was increased risk for progression to dementia in women who were taking hormone therapy which essentially flipped the field on its ahead because until that point everybody thought that estrogen was a protective factor.”

She said although this study found no association with dementia, she still thinks HT has a role to play and that it may just need to be better tailored to individuals.

“If you think about it, we have our tailored cocktail of hormones in our body and who’s to say that my hormones are going to be the same as yours? Why should you and I be put on the same hormone therapy and assume that will give us the same outcome? I think we could do a lot better with customization and calibration of hormones to aid in women’s health.”
 

Lifetime approach to dementia

Ms. Gong says future dementia risk-reduction strategies should consider sex-specific risk, and consider the reproductive events that took place in women’s lifespans as well as their entire hormone history when assessing dementia risk, to ensure that the strategies are sex sensitive.

Dr. Buckley agrees: “I don’t think we should ever think about dementia in terms of 65 onwards. We know this disease is insidious and it starts very, very early.”

Regarding limitations, the authors noted that it was a retrospective study that included self-reported measures of reproductive factors, which may be inherently subject to recall bias.

A coauthor does consultant work for Amgen, Freeline, and Kirin outside the submitted work. There were no other relevant financial disclosures.

Certain reproductive factors are associated with greater or lower risk of dementia, according to researchers who conducted a large population-based study with UK Biobank data.

Jessica Gong, a PhD candidate at the George Institute for Global Health at University of New South Wales in Australia, and coauthors found a greater dementia risk in women with early and late menarche, women who were younger when they first gave birth, and those who had had a hysterectomy, especially those who had a hysterectomy without concomitant oophorectomy or with a previous oophorectomy.

After controlling for key confounders, the researchers found lower risk of all-cause dementia if women had ever been pregnant, ever had an abortion, had a longer reproductive span, or had later menopause.

Use of oral contraceptive pills was associated with a lower dementia risk, they found.

In this study, there was no evidence that hormone therapy (HT) was associated with dementia risk (hazard ratio, 0.99, 95% confidence interval [0.90-1.09], P =.0828).

The analysis, published online April 5 in PLOS Medicine, comprised 273,240 women and 228,957 men without prevalent dementia.

The authors noted that dementia rates are increasing. Globally, 50 million people live with dementia, and the number is expected to triple by 2050, according to Alzheimer’s Disease International.

“Our study identified certain reproductive factors related to shorter exposure to endogenous estrogen were associated with increased risk of dementia, highlighting the susceptibility in dementia risk pertaining to women,” Ms. Gong told this publication.
 

Risk comparison of men and women

Men were included in this study to compare the association between number of children fathered and the risk of all-cause dementia, with the association in their female counterparts.

The U-shaped associations between the number of children and dementia risk were similar for both sexes, suggesting that the risk difference in women may not be associated with factors associated with childbearing

“It may be more related to social and behavioral factors in parenthood, rather than biological factors involved in childbearing,” Ms. Gong said.

Compared with those with two children, for those without children, the multiple adjusted HR (95% CI) was 1.18 (1.04, 1.33) (P = .027) for women and 1.10 (0.98-1.23) P = .164) for men.

For those with four or more children, the HR was 1.14 (0.98, 1.33) (P = .132) for women and 1.26 (1.10-1.45) (P = .003) for men.

Rachel Buckley, PhD, assistant professor of neurology with a dual appointment at Brigham and Women’s and Massachusetts General hospitals in Boston, told this publication she found the comparison of dementia risk with number of children in men and women “fascinating.”

She said the argument usually is that if women have had more births, then they have had more estrogen through their body because women get a huge injection of hormones in pregnancy.

“The idea is that the more pregnancies you have the more protected you are. But this study put that on its head, because if men and women are showing increased [dementia] risk in the number of children they have, it suggests there must be something about having the children – not necessarily the circulating hormones – that might be having an impact,” Dr. Buckley said.

“I had never thought to compare the number of children in men. I do find that very interesting,” she said.

As for the lack of a link between HT and dementia risk, in this study she said, she wouldn’t shut the door on that discussion just yet.

She noted the long history of controversy in the field about whether there is a protective factor against dementia for estrogen or whether exposure to estrogen leads to increased risk.

Before the landmark Women’s Health Initiative (WHI) study in the 1990s, she pointed out, there was evidence in many observational studies that women who had longer exposure to estrogen – whether that was earlier age at first period and later age at menopause combined or women had taken hormone therapy at some point, had less risk for dementia.

Dr. Buckley said that in a secondary outcome of WHI, however, “there was increased risk for progression to dementia in women who were taking hormone therapy which essentially flipped the field on its ahead because until that point everybody thought that estrogen was a protective factor.”

She said although this study found no association with dementia, she still thinks HT has a role to play and that it may just need to be better tailored to individuals.

“If you think about it, we have our tailored cocktail of hormones in our body and who’s to say that my hormones are going to be the same as yours? Why should you and I be put on the same hormone therapy and assume that will give us the same outcome? I think we could do a lot better with customization and calibration of hormones to aid in women’s health.”
 

Lifetime approach to dementia

Ms. Gong says future dementia risk-reduction strategies should consider sex-specific risk, and consider the reproductive events that took place in women’s lifespans as well as their entire hormone history when assessing dementia risk, to ensure that the strategies are sex sensitive.

Dr. Buckley agrees: “I don’t think we should ever think about dementia in terms of 65 onwards. We know this disease is insidious and it starts very, very early.”

Regarding limitations, the authors noted that it was a retrospective study that included self-reported measures of reproductive factors, which may be inherently subject to recall bias.

A coauthor does consultant work for Amgen, Freeline, and Kirin outside the submitted work. There were no other relevant financial disclosures.

The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.

“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.

Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.

But she was propelled into quite a different role when her mother was admitted to the hospital.

Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.

“She needed someone to translate what was going on because she didn’t feel well,” she added.

Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”

Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”

“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.

The experience prompted Dr. Kunz to share several “communication pearls” via Twitter. Her thread has since garnered thousands of “likes” and scores of comments and retweets.

She began the Twitter thread explaining what prompted her comments:

“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”

“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’

2.  End your patient visit with a summary of the plan for the day.

3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.

4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).

5. Many older [patients] get confused in the hospital. Repetition is a good thing.

6. Speak to a family member at least once per day to relay the plan.

7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’

8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).

9.  When possible, sit at eye level with your patient (I love these stools from @YNHH).

10. Take time to listen.”

Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”

Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”

Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.

“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.

Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”

@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”

Patients also shared experiences and offered suggestions.

“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”

Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”

Dr. Kunz said she was taken aback but pleased by the response to her Tweet.

“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”

Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.

“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”

In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.

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

The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.

“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.

Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.

But she was propelled into quite a different role when her mother was admitted to the hospital.

Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.

“She needed someone to translate what was going on because she didn’t feel well,” she added.

Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”

Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”

“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.

The experience prompted Dr. Kunz to share several “communication pearls” via Twitter. Her thread has since garnered thousands of “likes” and scores of comments and retweets.

She began the Twitter thread explaining what prompted her comments:

“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”

“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’

2.  End your patient visit with a summary of the plan for the day.

3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.

4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).

5. Many older [patients] get confused in the hospital. Repetition is a good thing.

6. Speak to a family member at least once per day to relay the plan.

7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’

8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).

9.  When possible, sit at eye level with your patient (I love these stools from @YNHH).

10. Take time to listen.”

Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”

Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”

Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.

“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.

Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”

@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”

Patients also shared experiences and offered suggestions.

“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”

Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”

Dr. Kunz said she was taken aback but pleased by the response to her Tweet.

“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”

Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.

“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”

In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.

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

The 5 days that she spent at her mother’s bedside were eye-opening for an oncologist used to being on the other side of the clinician–patient relationship.

“As a physician, I thought I had a unique perspective of things that were done well – and things that were not,” commented Pamela Kunz, MD.

Dr. Kunz, who was named the 2021 Woman Oncologist of the Year, is director of the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and of the Yale Cancer Center, New Haven, Conn.

But she was propelled into quite a different role when her mother was admitted to the hospital.

Her mom, who has trouble hearing, was easily confused by jargon and by “all of the people coming in and out with no introductions,” she explained.

“She needed someone to translate what was going on because she didn’t feel well,” she added.

Seeing inpatient care through her mother’s eyes was enlightening, and at times it was “shocking to be on the other side.”

Physicians get used to “checking boxes, getting through the day,” she said. “It’s easy to forget the human side.”

“Seeing a loved one sick, [struggling] through this – I just wished I had seen things done differently,” added Dr. Kunz.

The experience prompted Dr. Kunz to share several “communication pearls” via Twitter. Her thread has since garnered thousands of “likes” and scores of comments and retweets.

She began the Twitter thread explaining what prompted her comments:

“I spent many hours last week observing the practice of medicine while sitting at my mom’s hospital bedside and was reminded of some important communication pearls. Some musings ...”

“1. Introduce yourself by full name, role, and team and have ID badges visible. It can get very confusing for [patients] and family members with the number of people in and out of rooms. E.g. ‘My name is Dr. X. I’m the intern on the primary internal medicine team.’

2.  End your patient visit with a summary of the plan for the day.

3. Avoid medical jargon & speak slowly, clearly, and logically. Remember you are a teacher for your [patients] and their family.

4. Masks make it harder to hear, especially for [patients] with hearing loss (and they no longer have the aid of lip reading).

5. Many older [patients] get confused in the hospital. Repetition is a good thing.

6. Speak to a family member at least once per day to relay the plan.

7. Try to avoid last minute or surprise discharges – they make [patients] and family members anxious. Talk about discharge planning from day 1 and what milestones must occur prior to a safe discharge. ‘In order for you to leave the hospital, X, Y, X must happen.’

8. Talk with your [patients] about something other than what brought them to the hospital (a tip I once learned from a wise mentor).

9.  When possible, sit at eye level with your patient (I love these stools from @YNHH).

10. Take time to listen.”

Dr. Kunz closed with her golden rule: “Lastly, treat your patients how you would want your own family member treated.”

Twitter user @BrunaPellini replied: “I love this, especially ‘Treat your patients how you would want your own family member treated.’ My mom and grandma always said that to me since I was a med student, and this is definitely one of my core values.”

Other clinicians shared similar experiences, and some added to Dr. Kunz’s list.

“Agree entirely, love the list – and while none of us can always practice perfectly, my experiences with my own mother’s illness taught me an enormous amount about communication,” @hoperugo responded.

Twitter user @mariejacork added: “Everyone in health care please read ... if you are lucky enough to not have had a loved one unwell in hospital, these may get forgotten. Having sat with my dad for a few days before he died a few years ago, I felt a lot of these, and it changed my practice forever.”

@bjcohenmd provided additional advice: “And use the dry erase board that should be in every room. Never start a medication without explaining it. Many docs will see the patient and then go to the computer, decide to order a med, but never go back to explain it.”

Patients also shared experiences and offered suggestions.

“As a chronic pain patient I’d add – we know it’s frustrating you can’t cure us but PLEASE do not SIGH if we say something didn’t work or [tell] us to be more positive. Just say ‘I know this is very hard, I’m here to listen.’ We don’t expect a cure, we do expect to be believed,” said @ppenguinsmt. “It makes me feel like I’m causing distress to you if I say the pain has been unrelenting. I leave feeling worse. ...You may have heard 10 [people] in pain before me but this is MY only [appointment].”

Twitter user @KatieCahoots added: “These are perfect. I wish doctors would do this not only in the hospital but in the doctor’s office, as well. I would add one caveat: When you try not to use medical jargon, don’t dumb it down as though I don’t know anything about science or haven’t done any of my own research.”

Dr. Kunz said she was taken aback but pleased by the response to her Tweet.

“It’s an example of the human side of medicine, so it resonates with physicians and with patients,” she commented. Seeing through her mom’s eyes how care was provided made her realize that medical training should include more emphasis on communication, including “real-time feedback to interns, residents, fellows, and students.”

Yes, it takes time, and “we don’t all have a lot of extra time,” she acknowledged.

“But some of these elements don’t take that much more time to do. They can help build trust and can, in the long run, actually save time if patients understand and family members feel engaged and like they are participants,” she said. “I think a little time investment will go a long way.”

In her case, she very much appreciated the one trainee who tried to call her and update her about her mother’s care each afternoon. “I really valued that,” she said.

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

There is a two-lane bridge in my town. It is quaint and picturesque, and when we first moved here, I would gaze out at the water as I drove, letting my mind wander along with the seagulls drifting alongside the car. Until one day, crossing back over, I passed a school bus stopped in the other lane, and instead of waving back, the driver gave me such a fierce look of disapproval I felt like I’d been to the principal’s office. What had I done?

I started paying more attention to the pattern of the other cars on the bridge. Although it appeared to be a standard two-lane width, the lanes weren’t quite wide enough if a school bus or large truck needed to cross at the same time as a car coming from the opposite direction. They had to wait until the other lane was clear. It was an unwritten rule of the town that if you saw a school bus on the other side, you stopped your car and yielded the bridge to the bus. It took me weeks to figure this out. When I did, I felt like I finally belonged in the community. Before, I’d been an outsider.

This got me thinking about culture. Every place has its unwritten rules, whether a community or a workplace. But how do we know the culture of a place? It’s pretty much impossible until we experience it for ourselves.

When I did figure out the bridge, I had a little bit of anger, to be honest. How was I supposed to know about the lanes? There weren’t any signs. Geez.

Now, when I approach the bridge, I don’t even think about it. I know what to do if I see a bus coming.

But sometimes I remember that time of confusion before I deciphered the unwritten rule. I still have a twinge of guilt for having done something wrong, even though it hadn’t been my fault.

It reminded me of a memory from medical training. I was an MS4, and my ER rotation was in a busy county hospital with a level I trauma center. To say that the place was chaotic would be an understatement.

On the first morning, I was shown the chart rack (yes, this was back in the day of paper charts). Charts were placed in the order that patients arrived. Med students and residents were to take a chart in chronological order, go triage and assess the patient, and then find an attending. Once finished, you put the chart back on the rack and picked up the next one. This was the extent of my orientation to the ER.

The days and weeks of the rotation flew by. It was a busy and exciting time. By the end of the month, I’d come to feel a part of the team.

Until one day, after finishing discharging a patient, an attending asked me, “Where’s the billing sheet?”

I had no idea what she was talking about. No one had ever shown me a billing sheet. But by this point, as an MS4, I knew well that if an attending asked you something you didn’t know the answer to, you shouldn’t just say that you didn’t know. You should try to figure out if you could at least approximate an answer first.

As I scrambled in my mind to figure out what she was asking me, she took one look at the apprehension in my eyes and asked again, raising her voice, “You haven’t been doing the billing sheets?”

I thought back to the first day of the rotation. The cursory 30-second orientation. Chart rack. Take one. See the patient. Put it back. See the next patient. Nothing about billing sheets.

“No,” I said. “No one ever told me about – ”

But the attending didn’t care that I hadn’t been instructed on the billing sheets. She ripped into me, yelling about how she couldn’t believe I’d been working there the entire month and was not doing the billing sheets. She showed me what they were and where they were supposed to be going and, in front of the whole staff, treated me like not only the biggest idiot she’d ever worked with but that the hospital had ever seen.

As she berated me, I thought about all the patients I’d seen that month. All the billing sheets I hadn’t placed in the pile. All the attendings who hadn’t gotten credit for the patients they’d staffed with me.

But how could I have known? I wanted to ask. How could I have known if nobody showed me or told me?

It was like the bridge. I was in a new environment and somehow expected to know the rules without anyone telling me; and when I didn’t know, people treated me like I’d done it the wrong way on purpose.

I didn’t end up saying anything more to that attending. What could I have said? She had already unleashed a mountain of her pent-up anger at me.

What I did decide in that moment was that I would never be an attending like that.

Like the bridge, this memory years later can still make me feel guilt and shame for doing something wrong. Even though it wasn’t my fault.

I was thinking about this recently with the Match. Thousands of freshly graduated medical students embarking on their new positions as interns in teaching hospitals across the country.

For anyone who, like me, struggled with the unwritten rules of the medical culture with each new rotation, remember to be kind to yourself. If someone treats you poorly for not knowing something, you are not an idiot. You’ve worked incredibly hard to get where you are, and you deserve to be there.

For attendings and more senior trainees, remember what it was like to be starting in a new place. We all make mistakes, and often it’s simply because of a lack of information.

Trainees shouldn’t have to suffer and be made to feel like outsiders until they figure out the unwritten rules of the place. They belong.
 

Dr. Lycette is medical director of Providence Oncology and Hematology Care Clinic, Seaside, Ore. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

There is a two-lane bridge in my town. It is quaint and picturesque, and when we first moved here, I would gaze out at the water as I drove, letting my mind wander along with the seagulls drifting alongside the car. Until one day, crossing back over, I passed a school bus stopped in the other lane, and instead of waving back, the driver gave me such a fierce look of disapproval I felt like I’d been to the principal’s office. What had I done?

I started paying more attention to the pattern of the other cars on the bridge. Although it appeared to be a standard two-lane width, the lanes weren’t quite wide enough if a school bus or large truck needed to cross at the same time as a car coming from the opposite direction. They had to wait until the other lane was clear. It was an unwritten rule of the town that if you saw a school bus on the other side, you stopped your car and yielded the bridge to the bus. It took me weeks to figure this out. When I did, I felt like I finally belonged in the community. Before, I’d been an outsider.

This got me thinking about culture. Every place has its unwritten rules, whether a community or a workplace. But how do we know the culture of a place? It’s pretty much impossible until we experience it for ourselves.

When I did figure out the bridge, I had a little bit of anger, to be honest. How was I supposed to know about the lanes? There weren’t any signs. Geez.

Now, when I approach the bridge, I don’t even think about it. I know what to do if I see a bus coming.

But sometimes I remember that time of confusion before I deciphered the unwritten rule. I still have a twinge of guilt for having done something wrong, even though it hadn’t been my fault.

It reminded me of a memory from medical training. I was an MS4, and my ER rotation was in a busy county hospital with a level I trauma center. To say that the place was chaotic would be an understatement.

On the first morning, I was shown the chart rack (yes, this was back in the day of paper charts). Charts were placed in the order that patients arrived. Med students and residents were to take a chart in chronological order, go triage and assess the patient, and then find an attending. Once finished, you put the chart back on the rack and picked up the next one. This was the extent of my orientation to the ER.

The days and weeks of the rotation flew by. It was a busy and exciting time. By the end of the month, I’d come to feel a part of the team.

Until one day, after finishing discharging a patient, an attending asked me, “Where’s the billing sheet?”

I had no idea what she was talking about. No one had ever shown me a billing sheet. But by this point, as an MS4, I knew well that if an attending asked you something you didn’t know the answer to, you shouldn’t just say that you didn’t know. You should try to figure out if you could at least approximate an answer first.

As I scrambled in my mind to figure out what she was asking me, she took one look at the apprehension in my eyes and asked again, raising her voice, “You haven’t been doing the billing sheets?”

I thought back to the first day of the rotation. The cursory 30-second orientation. Chart rack. Take one. See the patient. Put it back. See the next patient. Nothing about billing sheets.

“No,” I said. “No one ever told me about – ”

But the attending didn’t care that I hadn’t been instructed on the billing sheets. She ripped into me, yelling about how she couldn’t believe I’d been working there the entire month and was not doing the billing sheets. She showed me what they were and where they were supposed to be going and, in front of the whole staff, treated me like not only the biggest idiot she’d ever worked with but that the hospital had ever seen.

As she berated me, I thought about all the patients I’d seen that month. All the billing sheets I hadn’t placed in the pile. All the attendings who hadn’t gotten credit for the patients they’d staffed with me.

But how could I have known? I wanted to ask. How could I have known if nobody showed me or told me?

It was like the bridge. I was in a new environment and somehow expected to know the rules without anyone telling me; and when I didn’t know, people treated me like I’d done it the wrong way on purpose.

I didn’t end up saying anything more to that attending. What could I have said? She had already unleashed a mountain of her pent-up anger at me.

What I did decide in that moment was that I would never be an attending like that.

Like the bridge, this memory years later can still make me feel guilt and shame for doing something wrong. Even though it wasn’t my fault.

I was thinking about this recently with the Match. Thousands of freshly graduated medical students embarking on their new positions as interns in teaching hospitals across the country.

For anyone who, like me, struggled with the unwritten rules of the medical culture with each new rotation, remember to be kind to yourself. If someone treats you poorly for not knowing something, you are not an idiot. You’ve worked incredibly hard to get where you are, and you deserve to be there.

For attendings and more senior trainees, remember what it was like to be starting in a new place. We all make mistakes, and often it’s simply because of a lack of information.

Trainees shouldn’t have to suffer and be made to feel like outsiders until they figure out the unwritten rules of the place. They belong.
 

Dr. Lycette is medical director of Providence Oncology and Hematology Care Clinic, Seaside, Ore. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

There is a two-lane bridge in my town. It is quaint and picturesque, and when we first moved here, I would gaze out at the water as I drove, letting my mind wander along with the seagulls drifting alongside the car. Until one day, crossing back over, I passed a school bus stopped in the other lane, and instead of waving back, the driver gave me such a fierce look of disapproval I felt like I’d been to the principal’s office. What had I done?

I started paying more attention to the pattern of the other cars on the bridge. Although it appeared to be a standard two-lane width, the lanes weren’t quite wide enough if a school bus or large truck needed to cross at the same time as a car coming from the opposite direction. They had to wait until the other lane was clear. It was an unwritten rule of the town that if you saw a school bus on the other side, you stopped your car and yielded the bridge to the bus. It took me weeks to figure this out. When I did, I felt like I finally belonged in the community. Before, I’d been an outsider.

This got me thinking about culture. Every place has its unwritten rules, whether a community or a workplace. But how do we know the culture of a place? It’s pretty much impossible until we experience it for ourselves.

When I did figure out the bridge, I had a little bit of anger, to be honest. How was I supposed to know about the lanes? There weren’t any signs. Geez.

Now, when I approach the bridge, I don’t even think about it. I know what to do if I see a bus coming.

But sometimes I remember that time of confusion before I deciphered the unwritten rule. I still have a twinge of guilt for having done something wrong, even though it hadn’t been my fault.

It reminded me of a memory from medical training. I was an MS4, and my ER rotation was in a busy county hospital with a level I trauma center. To say that the place was chaotic would be an understatement.

On the first morning, I was shown the chart rack (yes, this was back in the day of paper charts). Charts were placed in the order that patients arrived. Med students and residents were to take a chart in chronological order, go triage and assess the patient, and then find an attending. Once finished, you put the chart back on the rack and picked up the next one. This was the extent of my orientation to the ER.

The days and weeks of the rotation flew by. It was a busy and exciting time. By the end of the month, I’d come to feel a part of the team.

Until one day, after finishing discharging a patient, an attending asked me, “Where’s the billing sheet?”

I had no idea what she was talking about. No one had ever shown me a billing sheet. But by this point, as an MS4, I knew well that if an attending asked you something you didn’t know the answer to, you shouldn’t just say that you didn’t know. You should try to figure out if you could at least approximate an answer first.

As I scrambled in my mind to figure out what she was asking me, she took one look at the apprehension in my eyes and asked again, raising her voice, “You haven’t been doing the billing sheets?”

I thought back to the first day of the rotation. The cursory 30-second orientation. Chart rack. Take one. See the patient. Put it back. See the next patient. Nothing about billing sheets.

“No,” I said. “No one ever told me about – ”

But the attending didn’t care that I hadn’t been instructed on the billing sheets. She ripped into me, yelling about how she couldn’t believe I’d been working there the entire month and was not doing the billing sheets. She showed me what they were and where they were supposed to be going and, in front of the whole staff, treated me like not only the biggest idiot she’d ever worked with but that the hospital had ever seen.

As she berated me, I thought about all the patients I’d seen that month. All the billing sheets I hadn’t placed in the pile. All the attendings who hadn’t gotten credit for the patients they’d staffed with me.

But how could I have known? I wanted to ask. How could I have known if nobody showed me or told me?

It was like the bridge. I was in a new environment and somehow expected to know the rules without anyone telling me; and when I didn’t know, people treated me like I’d done it the wrong way on purpose.

I didn’t end up saying anything more to that attending. What could I have said? She had already unleashed a mountain of her pent-up anger at me.

What I did decide in that moment was that I would never be an attending like that.

Like the bridge, this memory years later can still make me feel guilt and shame for doing something wrong. Even though it wasn’t my fault.

I was thinking about this recently with the Match. Thousands of freshly graduated medical students embarking on their new positions as interns in teaching hospitals across the country.

For anyone who, like me, struggled with the unwritten rules of the medical culture with each new rotation, remember to be kind to yourself. If someone treats you poorly for not knowing something, you are not an idiot. You’ve worked incredibly hard to get where you are, and you deserve to be there.

For attendings and more senior trainees, remember what it was like to be starting in a new place. We all make mistakes, and often it’s simply because of a lack of information.

Trainees shouldn’t have to suffer and be made to feel like outsiders until they figure out the unwritten rules of the place. They belong.
 

Dr. Lycette is medical director of Providence Oncology and Hematology Care Clinic, Seaside, Ore. She disclosed no relevant conflicts of interest. A version of this article first appeared on Medscape.com.

Early results from a small trial of an investigative drug suggests it is safe and may improve executive function in patients with mild cognitive impairment (MCI) and mild dementia associated with Alzheimer’s disease. Patients performed better in cognitive testing after just 2 weeks, especially in areas of executive functioning. Clinicians involved in the study also reported improvements in patients’ ability to complete daily activities, especially in complex tasks such as using a computer, carrying out household chores, and managing their medications.

“It’s pretty incredible to see improvement over the course of a week to a week and a half,” said study investigator Aaron Koenig, MD, vice president of Early Clinical Development at Sage Therapeutics in Cambridge, Mass. “Not only are we seeing objective improvement, we’re also seeing a subjective benefit.”

The drug, SAGE-718, is also under study for MCI in patients with Huntington’s disease, the drug’s primary indication, and Parkinson’s disease.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Improved executive function

SAGE-718 is in a new class of drugs called positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors, which are thought to improve neuroplasticity.

For the phase 2a open-label LUMINARY trial, researchers enrolled 26 patients ages 50-80 years with Alzheimer’s disease who had MCI. Patients completed a battery of cognitive tests at the study outset, again at the end of treatment, and again after 28 days.

Participants received SAGE-718 daily for 2 weeks and were followed for another 2 weeks.

The study’s primary outcome was safety. Seven patients (26.9%) reported mild or moderate treatment-emergent adverse events (AEs), and there were no serious AEs or deaths.

However, after 14 days, researchers also noted improvements from baseline on multiple tests of executive functioning, learning, and memory. And at 28 days, participants demonstrated significantly better Montreal Cognitive Assessment scores, compared with baseline (+2.3 points; P < .05), suggesting improvement in global cognition.

“We know that in Alzheimer’s and other neurodegenerative conditions there is a change in cognition, the ability to think, the ability to do things,” Dr. Koenig said. “What we’ve seen with SAGE-718 to date, all the way back to our phase 1 studies, is a cognitively beneficial effect, but more specifically an improvement in executive functioning.”
 

Intentional small study design

Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement for the Alzheimer’s Association, said that because of the small study size, short follow-up, and limited data available in the conference abstract, “we cannot speculate about the efficacy of this investigational therapy.”

“Bigger picture, the real-world clinical meaningfulness of research results that are generated in highly controlled circumstances is an important question that is being discussed right now throughout the Alzheimer’s field,” he added.

However, Dr. Koenig countered that the small study design was intentional. “Over the course of a year, we can get to the answer in different patient populations rather than running these rather large and arduous trials that may pan out to not be positive,” he said.

“The purpose here is to say, directionally, are we seeing improvement that warrants further investigation? If you don’t see an effect in a small number of patients, if you don’t see that effect rather quickly, and if you don’t see an effect that should translate into something meaningful, we at SAGE believe that you may not have a drug there,” he added.

Sage Therapeutics plans to launch a phase 2b placebo-controlled trial later this year to study SAGE-718 in more Alzheimer’s patients over a longer period of time.

The study was funded by SAGE Therapeutics. Dr. Koenig is an employee of SAGE and reports no other conflicts. Dr. Griffin has disclosed no relevant financial relationships.  

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

Early results from a small trial of an investigative drug suggests it is safe and may improve executive function in patients with mild cognitive impairment (MCI) and mild dementia associated with Alzheimer’s disease. Patients performed better in cognitive testing after just 2 weeks, especially in areas of executive functioning. Clinicians involved in the study also reported improvements in patients’ ability to complete daily activities, especially in complex tasks such as using a computer, carrying out household chores, and managing their medications.

“It’s pretty incredible to see improvement over the course of a week to a week and a half,” said study investigator Aaron Koenig, MD, vice president of Early Clinical Development at Sage Therapeutics in Cambridge, Mass. “Not only are we seeing objective improvement, we’re also seeing a subjective benefit.”

The drug, SAGE-718, is also under study for MCI in patients with Huntington’s disease, the drug’s primary indication, and Parkinson’s disease.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Improved executive function

SAGE-718 is in a new class of drugs called positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors, which are thought to improve neuroplasticity.

For the phase 2a open-label LUMINARY trial, researchers enrolled 26 patients ages 50-80 years with Alzheimer’s disease who had MCI. Patients completed a battery of cognitive tests at the study outset, again at the end of treatment, and again after 28 days.

Participants received SAGE-718 daily for 2 weeks and were followed for another 2 weeks.

The study’s primary outcome was safety. Seven patients (26.9%) reported mild or moderate treatment-emergent adverse events (AEs), and there were no serious AEs or deaths.

However, after 14 days, researchers also noted improvements from baseline on multiple tests of executive functioning, learning, and memory. And at 28 days, participants demonstrated significantly better Montreal Cognitive Assessment scores, compared with baseline (+2.3 points; P < .05), suggesting improvement in global cognition.

“We know that in Alzheimer’s and other neurodegenerative conditions there is a change in cognition, the ability to think, the ability to do things,” Dr. Koenig said. “What we’ve seen with SAGE-718 to date, all the way back to our phase 1 studies, is a cognitively beneficial effect, but more specifically an improvement in executive functioning.”
 

Intentional small study design

Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement for the Alzheimer’s Association, said that because of the small study size, short follow-up, and limited data available in the conference abstract, “we cannot speculate about the efficacy of this investigational therapy.”

“Bigger picture, the real-world clinical meaningfulness of research results that are generated in highly controlled circumstances is an important question that is being discussed right now throughout the Alzheimer’s field,” he added.

However, Dr. Koenig countered that the small study design was intentional. “Over the course of a year, we can get to the answer in different patient populations rather than running these rather large and arduous trials that may pan out to not be positive,” he said.

“The purpose here is to say, directionally, are we seeing improvement that warrants further investigation? If you don’t see an effect in a small number of patients, if you don’t see that effect rather quickly, and if you don’t see an effect that should translate into something meaningful, we at SAGE believe that you may not have a drug there,” he added.

Sage Therapeutics plans to launch a phase 2b placebo-controlled trial later this year to study SAGE-718 in more Alzheimer’s patients over a longer period of time.

The study was funded by SAGE Therapeutics. Dr. Koenig is an employee of SAGE and reports no other conflicts. Dr. Griffin has disclosed no relevant financial relationships.  

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

Early results from a small trial of an investigative drug suggests it is safe and may improve executive function in patients with mild cognitive impairment (MCI) and mild dementia associated with Alzheimer’s disease. Patients performed better in cognitive testing after just 2 weeks, especially in areas of executive functioning. Clinicians involved in the study also reported improvements in patients’ ability to complete daily activities, especially in complex tasks such as using a computer, carrying out household chores, and managing their medications.

“It’s pretty incredible to see improvement over the course of a week to a week and a half,” said study investigator Aaron Koenig, MD, vice president of Early Clinical Development at Sage Therapeutics in Cambridge, Mass. “Not only are we seeing objective improvement, we’re also seeing a subjective benefit.”

The drug, SAGE-718, is also under study for MCI in patients with Huntington’s disease, the drug’s primary indication, and Parkinson’s disease.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Improved executive function

SAGE-718 is in a new class of drugs called positive allosteric modulator of N-methyl-D-aspartate (NMDA) receptors, which are thought to improve neuroplasticity.

For the phase 2a open-label LUMINARY trial, researchers enrolled 26 patients ages 50-80 years with Alzheimer’s disease who had MCI. Patients completed a battery of cognitive tests at the study outset, again at the end of treatment, and again after 28 days.

Participants received SAGE-718 daily for 2 weeks and were followed for another 2 weeks.

The study’s primary outcome was safety. Seven patients (26.9%) reported mild or moderate treatment-emergent adverse events (AEs), and there were no serious AEs or deaths.

However, after 14 days, researchers also noted improvements from baseline on multiple tests of executive functioning, learning, and memory. And at 28 days, participants demonstrated significantly better Montreal Cognitive Assessment scores, compared with baseline (+2.3 points; P < .05), suggesting improvement in global cognition.

“We know that in Alzheimer’s and other neurodegenerative conditions there is a change in cognition, the ability to think, the ability to do things,” Dr. Koenig said. “What we’ve seen with SAGE-718 to date, all the way back to our phase 1 studies, is a cognitively beneficial effect, but more specifically an improvement in executive functioning.”
 

Intentional small study design

Commenting on the findings, Percy Griffin, PhD, MSc, director of scientific engagement for the Alzheimer’s Association, said that because of the small study size, short follow-up, and limited data available in the conference abstract, “we cannot speculate about the efficacy of this investigational therapy.”

“Bigger picture, the real-world clinical meaningfulness of research results that are generated in highly controlled circumstances is an important question that is being discussed right now throughout the Alzheimer’s field,” he added.

However, Dr. Koenig countered that the small study design was intentional. “Over the course of a year, we can get to the answer in different patient populations rather than running these rather large and arduous trials that may pan out to not be positive,” he said.

“The purpose here is to say, directionally, are we seeing improvement that warrants further investigation? If you don’t see an effect in a small number of patients, if you don’t see that effect rather quickly, and if you don’t see an effect that should translate into something meaningful, we at SAGE believe that you may not have a drug there,” he added.

Sage Therapeutics plans to launch a phase 2b placebo-controlled trial later this year to study SAGE-718 in more Alzheimer’s patients over a longer period of time.

The study was funded by SAGE Therapeutics. Dr. Koenig is an employee of SAGE and reports no other conflicts. Dr. Griffin has disclosed no relevant financial relationships.  

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

An investigational drug that blocks the dopamine-1 (D1) receptor reduces tics and is safe and well tolerated in children with Tourette syndrome, a new study shows.

Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia, compared with placebo – a factor that may lead to better adherence.

For clinicians treating children with Tourette syndrome, the results suggest “help is on the way,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children’s Hospital Medical Center.

“There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects,” Dr. Gilbert said.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

First-in-class agent

Tourette syndrome is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.

“There’s a risk of injury, such as to the neck, with tics in childhood, so it’s good to have something that makes tics less severe and less socially impairing in junior high,” said Dr. Gilbert.

While tics generally diminish by adulthood, “about 10% of the patients we see as kids persist into adulthood enough to need medical interventions,” said Dr. Gilbert.

Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with Tourette syndrome. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Dr. Gilbert.

However, earlier studies in Tourette syndrome suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.

Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Dr. Gilbert.
 

Placebo-controlled trial

The new study included 149 patients with Tourette syndrome who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.

With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.

For each of the five areas, scores range from 0-5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.

Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.

The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.

Results on the YGTSS-TTS showed a significant improvement in the ecopipam group, compared with placebo groups (least square [LS] mean difference: -3.44; 95% confidence interval: -6.09 to -0.79; P = .011).

The analysis indicated a 30% reduction, with an effect size of 0.48, which is “pretty good,” said Dr. Gilbert. “The amount of change is comparable to other drugs that are marketed” to treat tics.

The drug was effective for younger as well as older children. Among those aged 6-11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).

A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Dr. Gilbert said is a more subjective measure of whether a patient’s life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points), compared with the placebo group (improvement of 0.5 points).

Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).

There were no metabolic or movement-related AEs or treatment-related serious AEs.

“This drug doesn’t cause weight gain at all,” said Dr. Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
 

Significant tic reduction

Commenting on the findings, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study “is promising” in that it demonstrates significant tic reduction, compared with placebo without significant side effects.

“Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future,” she said.

Dr. Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with Tourette syndrome during the COVID pandemic.

She noted that dopamine is an important neurotransmitter in the underlying pathophysiology of Tourette syndrome. In addition, although D2 receptor blockade can provide significant tic reduction, the “intolerable” side effects often linked to medications with this mechanism “can lead to discontinuation,” said Dr. Frey.

She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.

The study was supported by Emalex Biosciences. Dr. Gilbert and Dr. Frey report no relevant financial relationships.

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

An investigational drug that blocks the dopamine-1 (D1) receptor reduces tics and is safe and well tolerated in children with Tourette syndrome, a new study shows.

Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia, compared with placebo – a factor that may lead to better adherence.

For clinicians treating children with Tourette syndrome, the results suggest “help is on the way,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children’s Hospital Medical Center.

“There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects,” Dr. Gilbert said.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

First-in-class agent

Tourette syndrome is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.

“There’s a risk of injury, such as to the neck, with tics in childhood, so it’s good to have something that makes tics less severe and less socially impairing in junior high,” said Dr. Gilbert.

While tics generally diminish by adulthood, “about 10% of the patients we see as kids persist into adulthood enough to need medical interventions,” said Dr. Gilbert.

Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with Tourette syndrome. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Dr. Gilbert.

However, earlier studies in Tourette syndrome suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.

Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Dr. Gilbert.
 

Placebo-controlled trial

The new study included 149 patients with Tourette syndrome who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.

With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.

For each of the five areas, scores range from 0-5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.

Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.

The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.

Results on the YGTSS-TTS showed a significant improvement in the ecopipam group, compared with placebo groups (least square [LS] mean difference: -3.44; 95% confidence interval: -6.09 to -0.79; P = .011).

The analysis indicated a 30% reduction, with an effect size of 0.48, which is “pretty good,” said Dr. Gilbert. “The amount of change is comparable to other drugs that are marketed” to treat tics.

The drug was effective for younger as well as older children. Among those aged 6-11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).

A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Dr. Gilbert said is a more subjective measure of whether a patient’s life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points), compared with the placebo group (improvement of 0.5 points).

Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).

There were no metabolic or movement-related AEs or treatment-related serious AEs.

“This drug doesn’t cause weight gain at all,” said Dr. Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
 

Significant tic reduction

Commenting on the findings, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study “is promising” in that it demonstrates significant tic reduction, compared with placebo without significant side effects.

“Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future,” she said.

Dr. Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with Tourette syndrome during the COVID pandemic.

She noted that dopamine is an important neurotransmitter in the underlying pathophysiology of Tourette syndrome. In addition, although D2 receptor blockade can provide significant tic reduction, the “intolerable” side effects often linked to medications with this mechanism “can lead to discontinuation,” said Dr. Frey.

She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.

The study was supported by Emalex Biosciences. Dr. Gilbert and Dr. Frey report no relevant financial relationships.

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

An investigational drug that blocks the dopamine-1 (D1) receptor reduces tics and is safe and well tolerated in children with Tourette syndrome, a new study shows.

Importantly, unlike current medications for the disorder, ecocipam does not lead to weight gain, anxiety, depression, or tardive dyskinesia, compared with placebo – a factor that may lead to better adherence.

For clinicians treating children with Tourette syndrome, the results suggest “help is on the way,” said study investigator Donald Gilbert, MD, professor of pediatrics and neurology, University of Cincinnati Children’s Hospital Medical Center.

“There may be a drug available with a new mechanism of action that is effective to suppress tics without causing weight gain or unwanted neuropsychiatric side effects,” Dr. Gilbert said.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

First-in-class agent

Tourette syndrome is a neurologic condition that causes sudden repetitive involuntary muscle movements and sounds known as tics. These movements typically develop in childhood and worsen during adolescence.

“There’s a risk of injury, such as to the neck, with tics in childhood, so it’s good to have something that makes tics less severe and less socially impairing in junior high,” said Dr. Gilbert.

While tics generally diminish by adulthood, “about 10% of the patients we see as kids persist into adulthood enough to need medical interventions,” said Dr. Gilbert.

Ecopipam is a first-in-class selective D1 receptor antagonist in clinical development for pediatric patients with Tourette syndrome. The compound was previously tested without success in schizophrenia and in obesity, the idea being that because dopamine is linked to pleasure or reward, blocking it might result in weight loss, said Dr. Gilbert.

However, earlier studies in Tourette syndrome suggested that ecopipam reduces tics in children and adults and had low metabolic and movement-related adverse effects.

Drugs currently used to treat tics include haloperidol, pimocide, and aripiprazole. All of these agents block the dopamine-2 (D2) receptor and can cause weight gain and tardive dyskinesia, said Dr. Gilbert.
 

Placebo-controlled trial

The new study included 149 patients with Tourette syndrome who had a score of at least 20 on the Yale Global Tic Severity Total Tic Score (YGTSS-TTS). The scale measures five aspects of motor and vocal tics: the number, frequency, intensity, complexity, and interference.

With that scale, intensity assesses whether tics cause injury, complexity evaluates the number of muscle group, and interference assesses whether tics interrupt functions, such as speaking or walking.

For each of the five areas, scores range from 0-5, with higher scores indicating greater severity. The motor and vocal parts have a maximum of 25 points each, for a maximum total of 50.

Participants were randomly assigned to receive once-daily oral ecopipam or placebo. A 4-week titration period was followed by an 8-week maintenance period and then a 1-week tapering period.

The primary endpoint was mean change from baseline to week 12 in scores on the YGTSS-TTS.

Results on the YGTSS-TTS showed a significant improvement in the ecopipam group, compared with placebo groups (least square [LS] mean difference: -3.44; 95% confidence interval: -6.09 to -0.79; P = .011).

The analysis indicated a 30% reduction, with an effect size of 0.48, which is “pretty good,” said Dr. Gilbert. “The amount of change is comparable to other drugs that are marketed” to treat tics.

The drug was effective for younger as well as older children. Among those aged 6-11 years, the LS mean difference was -4.95 (95% CI: -9.99 to 0.10; P = .054), and for those aged 12 to 17 years, the LS mean difference was -3.37 (95% CI: -6.51 to -0.24; P = .035).

A key secondary endpoint was the score on the Clinical Global Impression of Tourette Syndrome Severity, which Dr. Gilbert said is a more subjective measure of whether a patient’s life has improved. Here, the mean change at week 12 was significant (P = .001) for the treated group (improvement of 0.91 points), compared with the placebo group (improvement of 0.5 points).

Researchers also assessed safety and tolerability. Treatment-related adverse events (AEs) occurred in 34% of patients taking ecopipam and in 21% of those taking placebo. The most common AEs were headache (9.2%), fatigue (6.6%), somnolence (6.6%), and restlessness (5.3%).

There were no metabolic or movement-related AEs or treatment-related serious AEs.

“This drug doesn’t cause weight gain at all,” said Dr. Gilbert. He noted that there was also no difference in the groups in terms of rates of depression, anxiety, or tardive dyskinesia.
 

Significant tic reduction

Commenting on the findings, Jessica Frey, MD, a movement disorders fellow at the University of Florida, said the new double-blind, placebo-controlled study “is promising” in that it demonstrates significant tic reduction, compared with placebo without significant side effects.

“Ecopipam could potentially expand pharmacologic treatment options for children and adolescents with Tourette syndrome in the near future,” she said.

Dr. Frey will also be presenting results at the meeting of a study showing a significant correlation between tic severity and social media use among adolescents with Tourette syndrome during the COVID pandemic.

She noted that dopamine is an important neurotransmitter in the underlying pathophysiology of Tourette syndrome. In addition, although D2 receptor blockade can provide significant tic reduction, the “intolerable” side effects often linked to medications with this mechanism “can lead to discontinuation,” said Dr. Frey.

She also noted that ecopipam has previously been evaluated in an open-label study and a follow-up placebo-controlled study that demonstrated safety as well as significant tic reduction.

The study was supported by Emalex Biosciences. Dr. Gilbert and Dr. Frey report no relevant financial relationships.

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

Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF). Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.

The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Inflammatory response

There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.

Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.

All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.

Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.

The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.

The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).

Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.

Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.

“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
 

Moving the needle forward

Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.

“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”

Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.

“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”

Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.

“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”

The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.

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

Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF). Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.

The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Inflammatory response

There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.

Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.

All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.

Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.

The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.

The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).

Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.

Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.

“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
 

Moving the needle forward

Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.

“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”

Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.

“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”

Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.

“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”

The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.

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

Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF). Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.

The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Inflammatory response

There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.

Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.

All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.

Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.

The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.

The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).

Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.

Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.

“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
 

Moving the needle forward

Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.

“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”

Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.

“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”

Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.

“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”

The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.

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

March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.

They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.

Spare me.

I’m not looking for any of that. In fact, I really don’t care.

Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.

It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.

People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.

I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.

It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise. After 23 years the only gratitude that means anything to me is the occasional heartfelt “thank you” from a patient.

And that’s all I need.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.

They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.

Spare me.

I’m not looking for any of that. In fact, I really don’t care.

Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.

It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.

People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.

I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.

It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise. After 23 years the only gratitude that means anything to me is the occasional heartfelt “thank you” from a patient.

And that’s all I need.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

March 30 was National Doctor’s Day, which resulted in my getting all kinds of generic emails from pharmaceutical reps, market research places, insurance companies, and the two hospitals I’m on staff at.

They all had similar meaningless platitudes thanking me for what I do, reassuring me that I’m appreciated, that I make the world a better place, yadda yadda yadda. The hospital even said I could swing by the medical staff office and pick up an “appreciation bag,” which I’m told contained a T-shirt, bottle of hand sanitizer, and a few other trinkets.

Spare me.

I’m not looking for any of that. In fact, I really don’t care.

Wishing me a “Happy Doctors Day” after spending the other 364 days denying my claims, refusing to cover tests or medications for my patients who need them (I don’t order these things for the hell of it, you know), telling me that I’m bringing down your Press Ganey scores, complaining about the copay that I have no control over, yelling at my staff for doing their jobs ... is pretty damn hollow.

It’s kind of like Mother’s Day: If you’re a jackass to your mom most of the year, sending her flowers on a Sunday in May doesn’t make it all right.

People also seem to forget that, in a small practice, my awesome staff is an extension of myself. Mistreating them, then wishing me a “Happy Doctor’s Day,” is also worthless.

I still like what I do. All the hassles from insurance companies, various administrators, the occasional angry patient … after all these years, they put a dent in it, but I still have no regrets about the course I’ve chosen. They can’t take away the happiness I get from helping those who need me.

It’s a job I love that’s allowed me to support my family and work with two wonderful staff members I’d never have met otherwise. After 23 years the only gratitude that means anything to me is the occasional heartfelt “thank you” from a patient.

And that’s all I need.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

SEATTLE – The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene.

LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.

The study protocol called for injection of the therapy into one eye and a placebo into the other, using the patient as his or own placebo control. The results in the treated eye were encouraging, though modest. “This is not hitting it out of the ballpark. But for people whose vision is devastated by this disease, it certainly is a first step,” said Nancy J. Newman, MD, during a press conference held March 29 in advance of the 2022 annual meeting of the American Academy of Neurology.

Dr. Newman also noted a surprise finding: Visual improvement also occurred in the placebo-control eye. This was noted in previous studies, called RESCUE and REVERSE, and follow-up studies in monkeys found viral vector in the unaffected eye 3-6 months after an injection. “This would imply some kind of transport within retrograde up the opposite optic nerve after crossing in the chiasm to the eye, but this is going to take a fair bit of work to know exactly how that happens,” said Dr. Newman

Unfortunately, the phase 3 REFLECT study was designed before that process was understood. “This was not a case-control study by person, it was by eye. And that was a mistake, because it turns out there is a does appear to be second eye effects. We do not have naive controls here that did not receive any injection at all in any eye. That’s something that we will [do going] forward,” said Dr. Newman.

Despite the problem with placebo, the results were encouraging. “Those patients who had both eyes injected with the drug did better than in those who had one eye injected with drug and one eye injected with placebo, suggesting some sort of dose effect. There were no adverse events other than what we would expect from injecting [into] eyes. Those treated with the drug had more ocular inflammation, as would also be expected, but all were easily treated with topical medications,” said Dr. Newman.
 

What are the long-term effects?

Natalia Rost, MD, who chairs the AAN Science Committee, commented after the presentation: “We’re quite impressed with advances in gene therapy. The question is, are there early indications that this improvement in vision will have a lasting effect?”

Dr. Newman responded that ongoing data from earlier studies are also encouraging regarding the long-term effect of the treatment. At 4 years, there was a difference of 16.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters equivalent between treated patients and natural history controls (P < .01), “which [does] suggest that this effect is maintained,” said Dr. Newman, who is a professor of ophthalmology and neurology at Emory University, Atlanta.

Dr. Rost also wondered if it would be possible to capture patients earlier in their disease process, in the hopes of countering degeneration before it becomes severe enough to impact vision. Dr. Newman answered by noting another surprise from the research. Previous studies had shown that intervention while only a single eye is affected had little impact on spread of the condition to the second eye, “which was very disappointing,” said Dr. Newman. When they stratified patients by time since vision loss, they found that those who received the therapy 6 months or later after vision loss had better responses than those who were treated earlier.

The mechanism of this counter-intuitive finding remains uncertain, “but we do know that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Our hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better,” said Dr. Newman.

The study included patients at 13 sites worldwide; 48 were treated bilaterally and 50 treated unilaterally. Just under 80% were male, the mean age was 31.5 years, and the mean duration of vision loss was 8.30 months.

After 1.5 years, the improvement in best-corrected visual acuity between second-affected eyes was stronger in the treatment eye, equivalent to +3 ETDRS letters. The first-affected eye improved by 19 ETDRS letters, and the second-affected eye improved by 16 (P < .0001). Improvement in placebo eyes was +13 ETDRS letters (P < .0001).

Dr. Rost has served on a scientific advisory board or data monitoring board for Omniox. Dr. Newman has consulted for GenSight, Santhera/Chiesi, and Neurophoenix, and has received research support from GenSight and Santhera/Chiesi.

SEATTLE – The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene.

LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.

The study protocol called for injection of the therapy into one eye and a placebo into the other, using the patient as his or own placebo control. The results in the treated eye were encouraging, though modest. “This is not hitting it out of the ballpark. But for people whose vision is devastated by this disease, it certainly is a first step,” said Nancy J. Newman, MD, during a press conference held March 29 in advance of the 2022 annual meeting of the American Academy of Neurology.

Dr. Newman also noted a surprise finding: Visual improvement also occurred in the placebo-control eye. This was noted in previous studies, called RESCUE and REVERSE, and follow-up studies in monkeys found viral vector in the unaffected eye 3-6 months after an injection. “This would imply some kind of transport within retrograde up the opposite optic nerve after crossing in the chiasm to the eye, but this is going to take a fair bit of work to know exactly how that happens,” said Dr. Newman

Unfortunately, the phase 3 REFLECT study was designed before that process was understood. “This was not a case-control study by person, it was by eye. And that was a mistake, because it turns out there is a does appear to be second eye effects. We do not have naive controls here that did not receive any injection at all in any eye. That’s something that we will [do going] forward,” said Dr. Newman.

Despite the problem with placebo, the results were encouraging. “Those patients who had both eyes injected with the drug did better than in those who had one eye injected with drug and one eye injected with placebo, suggesting some sort of dose effect. There were no adverse events other than what we would expect from injecting [into] eyes. Those treated with the drug had more ocular inflammation, as would also be expected, but all were easily treated with topical medications,” said Dr. Newman.
 

What are the long-term effects?

Natalia Rost, MD, who chairs the AAN Science Committee, commented after the presentation: “We’re quite impressed with advances in gene therapy. The question is, are there early indications that this improvement in vision will have a lasting effect?”

Dr. Newman responded that ongoing data from earlier studies are also encouraging regarding the long-term effect of the treatment. At 4 years, there was a difference of 16.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters equivalent between treated patients and natural history controls (P < .01), “which [does] suggest that this effect is maintained,” said Dr. Newman, who is a professor of ophthalmology and neurology at Emory University, Atlanta.

Dr. Rost also wondered if it would be possible to capture patients earlier in their disease process, in the hopes of countering degeneration before it becomes severe enough to impact vision. Dr. Newman answered by noting another surprise from the research. Previous studies had shown that intervention while only a single eye is affected had little impact on spread of the condition to the second eye, “which was very disappointing,” said Dr. Newman. When they stratified patients by time since vision loss, they found that those who received the therapy 6 months or later after vision loss had better responses than those who were treated earlier.

The mechanism of this counter-intuitive finding remains uncertain, “but we do know that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Our hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better,” said Dr. Newman.

The study included patients at 13 sites worldwide; 48 were treated bilaterally and 50 treated unilaterally. Just under 80% were male, the mean age was 31.5 years, and the mean duration of vision loss was 8.30 months.

After 1.5 years, the improvement in best-corrected visual acuity between second-affected eyes was stronger in the treatment eye, equivalent to +3 ETDRS letters. The first-affected eye improved by 19 ETDRS letters, and the second-affected eye improved by 16 (P < .0001). Improvement in placebo eyes was +13 ETDRS letters (P < .0001).

Dr. Rost has served on a scientific advisory board or data monitoring board for Omniox. Dr. Newman has consulted for GenSight, Santhera/Chiesi, and Neurophoenix, and has received research support from GenSight and Santhera/Chiesi.

SEATTLE – The latest data from a phase 3 clinical trial shows that gene therapy can counter visual degeneration associated with Leber hereditary optic neuropathy (LHON). The therapy, delivered by intravitreal injection, uses an adeno-associated virus vector to deliver a corrected copy of the mutated ND4 mitochondrial gene.

LHON is a rare, maternally inherited mitochondrial mutation that can cause blindness, most commonly in young men, though it does not happen in all individuals with the mutation. The condition often starts with blindness in one eye, accompanied or followed shortly by blindness in the second eye. Researchers believe that the injected viral vector gets taken up retinal ganglion cells, where the mutated gene interferes with vision. Once synthesized, a mitochondria-targeting sequence facilitates transport of the protein to the mitochondria.

The study protocol called for injection of the therapy into one eye and a placebo into the other, using the patient as his or own placebo control. The results in the treated eye were encouraging, though modest. “This is not hitting it out of the ballpark. But for people whose vision is devastated by this disease, it certainly is a first step,” said Nancy J. Newman, MD, during a press conference held March 29 in advance of the 2022 annual meeting of the American Academy of Neurology.

Dr. Newman also noted a surprise finding: Visual improvement also occurred in the placebo-control eye. This was noted in previous studies, called RESCUE and REVERSE, and follow-up studies in monkeys found viral vector in the unaffected eye 3-6 months after an injection. “This would imply some kind of transport within retrograde up the opposite optic nerve after crossing in the chiasm to the eye, but this is going to take a fair bit of work to know exactly how that happens,” said Dr. Newman

Unfortunately, the phase 3 REFLECT study was designed before that process was understood. “This was not a case-control study by person, it was by eye. And that was a mistake, because it turns out there is a does appear to be second eye effects. We do not have naive controls here that did not receive any injection at all in any eye. That’s something that we will [do going] forward,” said Dr. Newman.

Despite the problem with placebo, the results were encouraging. “Those patients who had both eyes injected with the drug did better than in those who had one eye injected with drug and one eye injected with placebo, suggesting some sort of dose effect. There were no adverse events other than what we would expect from injecting [into] eyes. Those treated with the drug had more ocular inflammation, as would also be expected, but all were easily treated with topical medications,” said Dr. Newman.
 

What are the long-term effects?

Natalia Rost, MD, who chairs the AAN Science Committee, commented after the presentation: “We’re quite impressed with advances in gene therapy. The question is, are there early indications that this improvement in vision will have a lasting effect?”

Dr. Newman responded that ongoing data from earlier studies are also encouraging regarding the long-term effect of the treatment. At 4 years, there was a difference of 16.5 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters equivalent between treated patients and natural history controls (P < .01), “which [does] suggest that this effect is maintained,” said Dr. Newman, who is a professor of ophthalmology and neurology at Emory University, Atlanta.

Dr. Rost also wondered if it would be possible to capture patients earlier in their disease process, in the hopes of countering degeneration before it becomes severe enough to impact vision. Dr. Newman answered by noting another surprise from the research. Previous studies had shown that intervention while only a single eye is affected had little impact on spread of the condition to the second eye, “which was very disappointing,” said Dr. Newman. When they stratified patients by time since vision loss, they found that those who received the therapy 6 months or later after vision loss had better responses than those who were treated earlier.

The mechanism of this counter-intuitive finding remains uncertain, “but we do know that acutely in this disease when people are just starting to lose this vision, during the first couple of months, they get swelling of the axons from these retinal ganglion cells. Our hypothesis is that swelling may actually act as a barrier for the drug to get into the retinal ganglion cell bodies themselves and be transfected. So it turns out that earlier may not be better,” said Dr. Newman.

The study included patients at 13 sites worldwide; 48 were treated bilaterally and 50 treated unilaterally. Just under 80% were male, the mean age was 31.5 years, and the mean duration of vision loss was 8.30 months.

After 1.5 years, the improvement in best-corrected visual acuity between second-affected eyes was stronger in the treatment eye, equivalent to +3 ETDRS letters. The first-affected eye improved by 19 ETDRS letters, and the second-affected eye improved by 16 (P < .0001). Improvement in placebo eyes was +13 ETDRS letters (P < .0001).

Dr. Rost has served on a scientific advisory board or data monitoring board for Omniox. Dr. Newman has consulted for GenSight, Santhera/Chiesi, and Neurophoenix, and has received research support from GenSight and Santhera/Chiesi.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.

Atypical anxiety in adults with Parkinson’s disease ranged from 15% to 51% in a systematic review of 60 studies.

Anxiety is common in Parkinson’s disease (PD) and has been shown to increase functional disability and decrease quality of life, but atypical presentations of anxiety are underrecognized and often undertreated in PD patients, wrote Nadeeka N. Dissanayaka, PhD, of the University of Queensland, Brisbane, Australia, and colleagues.

Courtesy University of Queensland

In a study published in the American Journal of Geriatric Psychiatry , the researchers conducted a systematic review of 60 studies to better characterize atypical PD-related anxiety. Fourteen studies involved Anxiety Not Otherwise Specified (NOS), 31 included fluctuating anxiety symptoms, and 22 included Fear of Falling (FOF).

Overall, the average prevalence rate for anxiety disorders in the PD population was 31%.

Anxiety NOS, fluctuating anxiety, and FOF accounted for a weighted mean prevalence of 14.9%, 34.19%, and 51.5%, respectively.

The symptomatology of anxiety NOS included psychological distress about the PD diagnosis, insecurity about the future, fear of losing control of motor and bodily functions, and social embarrassment. Clinically, anxiety NOS was associated with a range of factors including minor depression, on-off motor symptoms, muscle cramps, poor quality of life, and gait impairment.

The symptomatology of fluctuating anxiety was assessed in 9 studies of the “on” motor state and 16 studies of both “on” and “off.” Symptoms associated with the off state included panic attacks, feeling anxious or sad, and avoiding situations, as well as palpitations, dizziness, chills, and hot flashes.

Clinically, studies showed that anxiety was more severe in the off-medication state, and symptoms were reduced in the on state. Data from some studies showed that fluctuating anxiety was more common in PD patients who were female, and who had a younger age of PD onset and longer disease duration.

The symptomatology of FOF included associations between FOF and difficulty with walking and gait: Using a walker or other device, more frequent freezing in place, hesitation when turning, and slower speed while walking. Clinically, characteristics associated with FOF included older age, needing assistance for activities of daily living, a history of falls, and reduced quality of life.

The results of the review were limited by several factors including the varying assessment techniques, and the lack of data on treatment for atypical anxiety in PD, the researchers noted. “To our knowledge there are no treatment trials focused on Anxiety NOS,” and studies on the treatment of fluctuating anxiety and FOF are preliminary, they said.

However, the results support the need for early identification and classification of PD-related anxiety to improve treatment strategies and long-term outcomes, the researchers concluded. In the absence of evidence-based treatment strategies, “Given the heterogeneity of anxiety presentations in PD, the importance of tailoring interventions to meet the specific needs and unique symptom profiles of each individual cannot be overstated,” and routine screening of PD patients for anxiety every 6-12 months is recommended, they emphasized.

Dr. Dissanayaka disclosed support from the National Health and Medical Research Boosting Dementia Research Leadership Fellowship.