Neurology

Food insecurity was significantly associated with migraine prevalence in young adults, according to Jason M. Nagata, MD, of the University of California, San Francisco, and associates.

Data were collected from a cross-sectional, nationally representative set of 14,786 young adults in the United States aged 24-32 years who participated in the 2008 National Longitudinal Study of Adolescent to Adult Health, the investigators wrote in a research letter published in JAMA Neurology.

Food insecurity was assessed by self-report through the interview question, “In the past 12 months, was there a time when (you/your household were/was) worried whether food would run out before you would get money to buy more?” Migraine was assessed by a positive answer to the interview question, “Has a doctor, nurse, or other health care professional ever told you that you have or had migraine headaches?”

In all, 1,647 study participants (11%) reported food insecurity; the prevalence of migraine in this group was 23.9%, compared with a prevalence of 13.6% in participants who did not report food insecurity. The association between food insecurity and migraine was significant both before (odds ratio, 2.00; 95% confidence interval, 1.68-2.38; P less than .001) and after adjustment (adjusted OR, .58; 95% CI, 1.30-1.95; P less than .001).

“Health care clinicians caring for persons who experience migraine should consider screening for food insecurity as a potential contributor to migraine exacerbations and provide referrals to programs such as the Supplemental Nutrition Assistance Program [formerly the Food Stamp Program] when appropriate,” the investigators concluded (JAMA Neurol. 2019 Jun 24. doi: 10.1001/jamaneurol.2019.1663).

No conflicts of interest were reported. The study was supported by grants from the University of California Global Food Initiative Fellowship, the American Academy of Pediatrics, the American Pediatric Society, and the Norman Schlossberger Research Fund from the University of California.

[email protected]

Food insecurity was significantly associated with migraine prevalence in young adults, according to Jason M. Nagata, MD, of the University of California, San Francisco, and associates.

Data were collected from a cross-sectional, nationally representative set of 14,786 young adults in the United States aged 24-32 years who participated in the 2008 National Longitudinal Study of Adolescent to Adult Health, the investigators wrote in a research letter published in JAMA Neurology.

Food insecurity was assessed by self-report through the interview question, “In the past 12 months, was there a time when (you/your household were/was) worried whether food would run out before you would get money to buy more?” Migraine was assessed by a positive answer to the interview question, “Has a doctor, nurse, or other health care professional ever told you that you have or had migraine headaches?”

In all, 1,647 study participants (11%) reported food insecurity; the prevalence of migraine in this group was 23.9%, compared with a prevalence of 13.6% in participants who did not report food insecurity. The association between food insecurity and migraine was significant both before (odds ratio, 2.00; 95% confidence interval, 1.68-2.38; P less than .001) and after adjustment (adjusted OR, .58; 95% CI, 1.30-1.95; P less than .001).

“Health care clinicians caring for persons who experience migraine should consider screening for food insecurity as a potential contributor to migraine exacerbations and provide referrals to programs such as the Supplemental Nutrition Assistance Program [formerly the Food Stamp Program] when appropriate,” the investigators concluded (JAMA Neurol. 2019 Jun 24. doi: 10.1001/jamaneurol.2019.1663).

No conflicts of interest were reported. The study was supported by grants from the University of California Global Food Initiative Fellowship, the American Academy of Pediatrics, the American Pediatric Society, and the Norman Schlossberger Research Fund from the University of California.

[email protected]

Food insecurity was significantly associated with migraine prevalence in young adults, according to Jason M. Nagata, MD, of the University of California, San Francisco, and associates.

Data were collected from a cross-sectional, nationally representative set of 14,786 young adults in the United States aged 24-32 years who participated in the 2008 National Longitudinal Study of Adolescent to Adult Health, the investigators wrote in a research letter published in JAMA Neurology.

Food insecurity was assessed by self-report through the interview question, “In the past 12 months, was there a time when (you/your household were/was) worried whether food would run out before you would get money to buy more?” Migraine was assessed by a positive answer to the interview question, “Has a doctor, nurse, or other health care professional ever told you that you have or had migraine headaches?”

In all, 1,647 study participants (11%) reported food insecurity; the prevalence of migraine in this group was 23.9%, compared with a prevalence of 13.6% in participants who did not report food insecurity. The association between food insecurity and migraine was significant both before (odds ratio, 2.00; 95% confidence interval, 1.68-2.38; P less than .001) and after adjustment (adjusted OR, .58; 95% CI, 1.30-1.95; P less than .001).

“Health care clinicians caring for persons who experience migraine should consider screening for food insecurity as a potential contributor to migraine exacerbations and provide referrals to programs such as the Supplemental Nutrition Assistance Program [formerly the Food Stamp Program] when appropriate,” the investigators concluded (JAMA Neurol. 2019 Jun 24. doi: 10.1001/jamaneurol.2019.1663).

No conflicts of interest were reported. The study was supported by grants from the University of California Global Food Initiative Fellowship, the American Academy of Pediatrics, the American Pediatric Society, and the Norman Schlossberger Research Fund from the University of California.

[email protected]

SAN ANTONIO – Episodic migraine patients benefit from mindfulness-based stress reduction training, according to new research. The intervention reduced headache frequency, slightly increased whole-brain gray matter volume, and reduced symptoms of anxiety, depression, and stress.

stockdevil/Thinkstock

The gray matter findings may indicate opportunities for therapeutic targets, while the psychosocial findings are important in understanding migraine burden, treatment response, and personalized medicine opportunities, Shana Burrowes, PhD, a postdoctoral associate at Boston University, said at the annual meeting of the College on Problems of Drug Dependence.

In a session focused on exploring alternatives to opioids for pain treatment, Dr. Burrowes described interim results of a randomized, controlled trial testing the effectiveness of mindfulness-based stress reduction (MBSR) training for managing migraine.

In discussing the rationale for study endpoints, she explained a three-pronged model for understanding migraine. Those elements include the symptoms themselves – unilateral throbbing pain, nausea, and photophobia – and the psychosocial symptoms and comorbidities, including anxiety, depression, stress, and catastrophizing. Up to 30%* of migraine patients have comorbid depression.

Those two prongs have a bidirectional relationship, since each increases the risk of the other. For example, frequent migraine can leave people feeling anxious about when their next migraine will occur, and that anxiety can increase the risk of it occurring.

Both elements lead to the third prong, which is change in gray matter volume. “If you’re a patient with migraine, an MRI on your brain is going to look different from somebody who does not have migraine,” Dr. Burrowes said. “With all these things going on in a patient, a migraine patient is actually pretty difficult to treat.”

Therefore, the researchers focused on outcomes from each of these three domains: gray matter volume in MRI; headache frequency as a clinical outcome; and the psychosocial comorbidities of anxiety, stress, and depression.

Study participants included 98 patients with episodic migraine, defined as fewer than 15 headache days a month, and 27 controls* matched by demographics to the patients and without any chronic pain conditions. The groups were 92% female and had similar ratios of whites (75% and 77%) and college graduates (95% and 96%).

Only the patients were randomized to the two interventions, one a training on MBSR and the other focusing on stress management for headache (SMH).

The MBSR training involved group sessions, eight 2.5-hour meditation sessions, at-home practice, a half-day retreat, and then an additional four biweekly sessions. The mindfulness training specifically focused on intentionally paying attention in the moment without judgment. The SMH arm focused on education for managing headache symptoms, stress, sleep hygiene, and diet, but it did not involve any specific skills training, such as relaxation training.

All participants, including healthy controls, underwent clinical assessment and baseline MRI and psychosocial questionnaires, followed by MRI and psychosocial questionnaire follow-ups at 3 and 6 months. MRI imaging focused on the whole brain and on the bilateral insula, dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus. Patients also kept headache diaries throughout the trial.

Both intervention groups showed an increase in gray matter volume over 6 months, compared with healthy controls: 1.3% in the whole brain for SMH participants and 1.01% in the MBSR patients, compared with –1.37% in healthy participants. In the right superior frontal gyrus, gray matter volume also increased 2.62% in SMH participants and 1.25% in MBSR patients but decreased 0.19% in healthy participants.

Dr. Burrowes said she could not share specific findings on headache frequency and psychosocial outcomes because her team’s research is currently under review. Overall, however, headache frequency declined more than 50% post intervention, and 39% of migraine patients responded to the therapy.

In addition, anxiety, stress, and depression symptoms all saw improvements from MBSR and slightly but significantly mediated the effect of MBSR on migraine reduction.

Dr. Burrowes reported having no disclosures.

*The story was updated 6/20/2019.

SAN ANTONIO – Episodic migraine patients benefit from mindfulness-based stress reduction training, according to new research. The intervention reduced headache frequency, slightly increased whole-brain gray matter volume, and reduced symptoms of anxiety, depression, and stress.

stockdevil/Thinkstock

The gray matter findings may indicate opportunities for therapeutic targets, while the psychosocial findings are important in understanding migraine burden, treatment response, and personalized medicine opportunities, Shana Burrowes, PhD, a postdoctoral associate at Boston University, said at the annual meeting of the College on Problems of Drug Dependence.

In a session focused on exploring alternatives to opioids for pain treatment, Dr. Burrowes described interim results of a randomized, controlled trial testing the effectiveness of mindfulness-based stress reduction (MBSR) training for managing migraine.

In discussing the rationale for study endpoints, she explained a three-pronged model for understanding migraine. Those elements include the symptoms themselves – unilateral throbbing pain, nausea, and photophobia – and the psychosocial symptoms and comorbidities, including anxiety, depression, stress, and catastrophizing. Up to 30%* of migraine patients have comorbid depression.

Those two prongs have a bidirectional relationship, since each increases the risk of the other. For example, frequent migraine can leave people feeling anxious about when their next migraine will occur, and that anxiety can increase the risk of it occurring.

Both elements lead to the third prong, which is change in gray matter volume. “If you’re a patient with migraine, an MRI on your brain is going to look different from somebody who does not have migraine,” Dr. Burrowes said. “With all these things going on in a patient, a migraine patient is actually pretty difficult to treat.”

Therefore, the researchers focused on outcomes from each of these three domains: gray matter volume in MRI; headache frequency as a clinical outcome; and the psychosocial comorbidities of anxiety, stress, and depression.

Study participants included 98 patients with episodic migraine, defined as fewer than 15 headache days a month, and 27 controls* matched by demographics to the patients and without any chronic pain conditions. The groups were 92% female and had similar ratios of whites (75% and 77%) and college graduates (95% and 96%).

Only the patients were randomized to the two interventions, one a training on MBSR and the other focusing on stress management for headache (SMH).

The MBSR training involved group sessions, eight 2.5-hour meditation sessions, at-home practice, a half-day retreat, and then an additional four biweekly sessions. The mindfulness training specifically focused on intentionally paying attention in the moment without judgment. The SMH arm focused on education for managing headache symptoms, stress, sleep hygiene, and diet, but it did not involve any specific skills training, such as relaxation training.

All participants, including healthy controls, underwent clinical assessment and baseline MRI and psychosocial questionnaires, followed by MRI and psychosocial questionnaire follow-ups at 3 and 6 months. MRI imaging focused on the whole brain and on the bilateral insula, dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus. Patients also kept headache diaries throughout the trial.

Both intervention groups showed an increase in gray matter volume over 6 months, compared with healthy controls: 1.3% in the whole brain for SMH participants and 1.01% in the MBSR patients, compared with –1.37% in healthy participants. In the right superior frontal gyrus, gray matter volume also increased 2.62% in SMH participants and 1.25% in MBSR patients but decreased 0.19% in healthy participants.

Dr. Burrowes said she could not share specific findings on headache frequency and psychosocial outcomes because her team’s research is currently under review. Overall, however, headache frequency declined more than 50% post intervention, and 39% of migraine patients responded to the therapy.

In addition, anxiety, stress, and depression symptoms all saw improvements from MBSR and slightly but significantly mediated the effect of MBSR on migraine reduction.

Dr. Burrowes reported having no disclosures.

*The story was updated 6/20/2019.

SAN ANTONIO – Episodic migraine patients benefit from mindfulness-based stress reduction training, according to new research. The intervention reduced headache frequency, slightly increased whole-brain gray matter volume, and reduced symptoms of anxiety, depression, and stress.

stockdevil/Thinkstock

The gray matter findings may indicate opportunities for therapeutic targets, while the psychosocial findings are important in understanding migraine burden, treatment response, and personalized medicine opportunities, Shana Burrowes, PhD, a postdoctoral associate at Boston University, said at the annual meeting of the College on Problems of Drug Dependence.

In a session focused on exploring alternatives to opioids for pain treatment, Dr. Burrowes described interim results of a randomized, controlled trial testing the effectiveness of mindfulness-based stress reduction (MBSR) training for managing migraine.

In discussing the rationale for study endpoints, she explained a three-pronged model for understanding migraine. Those elements include the symptoms themselves – unilateral throbbing pain, nausea, and photophobia – and the psychosocial symptoms and comorbidities, including anxiety, depression, stress, and catastrophizing. Up to 30%* of migraine patients have comorbid depression.

Those two prongs have a bidirectional relationship, since each increases the risk of the other. For example, frequent migraine can leave people feeling anxious about when their next migraine will occur, and that anxiety can increase the risk of it occurring.

Both elements lead to the third prong, which is change in gray matter volume. “If you’re a patient with migraine, an MRI on your brain is going to look different from somebody who does not have migraine,” Dr. Burrowes said. “With all these things going on in a patient, a migraine patient is actually pretty difficult to treat.”

Therefore, the researchers focused on outcomes from each of these three domains: gray matter volume in MRI; headache frequency as a clinical outcome; and the psychosocial comorbidities of anxiety, stress, and depression.

Study participants included 98 patients with episodic migraine, defined as fewer than 15 headache days a month, and 27 controls* matched by demographics to the patients and without any chronic pain conditions. The groups were 92% female and had similar ratios of whites (75% and 77%) and college graduates (95% and 96%).

Only the patients were randomized to the two interventions, one a training on MBSR and the other focusing on stress management for headache (SMH).

The MBSR training involved group sessions, eight 2.5-hour meditation sessions, at-home practice, a half-day retreat, and then an additional four biweekly sessions. The mindfulness training specifically focused on intentionally paying attention in the moment without judgment. The SMH arm focused on education for managing headache symptoms, stress, sleep hygiene, and diet, but it did not involve any specific skills training, such as relaxation training.

All participants, including healthy controls, underwent clinical assessment and baseline MRI and psychosocial questionnaires, followed by MRI and psychosocial questionnaire follow-ups at 3 and 6 months. MRI imaging focused on the whole brain and on the bilateral insula, dorsolateral prefrontal cortex, anterior cingulate cortex, and superior frontal gyrus. Patients also kept headache diaries throughout the trial.

Both intervention groups showed an increase in gray matter volume over 6 months, compared with healthy controls: 1.3% in the whole brain for SMH participants and 1.01% in the MBSR patients, compared with –1.37% in healthy participants. In the right superior frontal gyrus, gray matter volume also increased 2.62% in SMH participants and 1.25% in MBSR patients but decreased 0.19% in healthy participants.

Dr. Burrowes said she could not share specific findings on headache frequency and psychosocial outcomes because her team’s research is currently under review. Overall, however, headache frequency declined more than 50% post intervention, and 39% of migraine patients responded to the therapy.

In addition, anxiety, stress, and depression symptoms all saw improvements from MBSR and slightly but significantly mediated the effect of MBSR on migraine reduction.

Dr. Burrowes reported having no disclosures.

*The story was updated 6/20/2019.

SAN ANTONIO – Prescription opioid abuse has continued declining since 2011, but opioids remain far more commonly abused than other prescription drugs, including gabapentin and pregabalin, new research shows.

“Both gabapentin and pregabalin are abused but at rates that are 6-56 times less frequent than for opioid analgesics,” wrote Kofi Asomaning, DSci, of Pfizer, and associates at Pfizer and Denver Health’s Rocky Mountain Poison and Drug Center.

“Gabapentin is generally more frequently abused than pregabalin,” they reported in a research poster at the annual meeting of the College on Problems of Drug Dependence.

The researchers analyzed data from the RADARS System Survey of Non-Medical Use of Prescription Drugs Program (NMURx), the RADARS System Treatment Center Programs Combined, and the American Association of Poison Control Centers National Poison Data System (NPDS).

All those use self-reported data. The first is a confidential, anonymous web-based survey used to estimate population-level prevalence, and the second surveys patients with opioid use disorder entering treatment. The NPDS tracks all cases reported to poison control centers nationally.


Analysis of the NMURx data revealed similar lifetime abuse prevalence rates for gabapentin and pregabalin at 0.4%, several magnitudes lower than the 5.3% rate identified with opioids.

Gabapentin, however, had higher rates of abuse in the past month in the Treatment Center Programs Combined. For the third to fourth quarter of 2017, 0.12 per 100,000 population reportedly abused gabapentin, compared with 0.01 per 100,000 for pregabalin. The rate for past-month abuse of opioids was 0.79 per 100,000.

A similar pattern for the same quarter emerged from the NPDS data: Rate of gabapentin abuse was 0.06 per 100,000, rate for pregabalin was 0.01 per 100,000, and rate for opioids was 0.40 per 100,000.

Both pregabalin and opioids were predominantly ingested, though a very small amount of each was inhaled and a similarly small amount of opioids was injected. Data on exposure route for gabapentin were not provided, though it was used more frequently than pregabalin.

The research was funded by Pfizer. The RADARS system is owned by Denver Health and Hospital Authority under the Colorado state government. RADARS receives some funding from pharmaceutical industry subscriptions. Dr. Asomaning and Diane L. Martire, MD, MPH, are Pfizer employees who have financial interests with Pfizer.

SAN ANTONIO – Prescription opioid abuse has continued declining since 2011, but opioids remain far more commonly abused than other prescription drugs, including gabapentin and pregabalin, new research shows.

“Both gabapentin and pregabalin are abused but at rates that are 6-56 times less frequent than for opioid analgesics,” wrote Kofi Asomaning, DSci, of Pfizer, and associates at Pfizer and Denver Health’s Rocky Mountain Poison and Drug Center.

“Gabapentin is generally more frequently abused than pregabalin,” they reported in a research poster at the annual meeting of the College on Problems of Drug Dependence.

The researchers analyzed data from the RADARS System Survey of Non-Medical Use of Prescription Drugs Program (NMURx), the RADARS System Treatment Center Programs Combined, and the American Association of Poison Control Centers National Poison Data System (NPDS).

All those use self-reported data. The first is a confidential, anonymous web-based survey used to estimate population-level prevalence, and the second surveys patients with opioid use disorder entering treatment. The NPDS tracks all cases reported to poison control centers nationally.


Analysis of the NMURx data revealed similar lifetime abuse prevalence rates for gabapentin and pregabalin at 0.4%, several magnitudes lower than the 5.3% rate identified with opioids.

Gabapentin, however, had higher rates of abuse in the past month in the Treatment Center Programs Combined. For the third to fourth quarter of 2017, 0.12 per 100,000 population reportedly abused gabapentin, compared with 0.01 per 100,000 for pregabalin. The rate for past-month abuse of opioids was 0.79 per 100,000.

A similar pattern for the same quarter emerged from the NPDS data: Rate of gabapentin abuse was 0.06 per 100,000, rate for pregabalin was 0.01 per 100,000, and rate for opioids was 0.40 per 100,000.

Both pregabalin and opioids were predominantly ingested, though a very small amount of each was inhaled and a similarly small amount of opioids was injected. Data on exposure route for gabapentin were not provided, though it was used more frequently than pregabalin.

The research was funded by Pfizer. The RADARS system is owned by Denver Health and Hospital Authority under the Colorado state government. RADARS receives some funding from pharmaceutical industry subscriptions. Dr. Asomaning and Diane L. Martire, MD, MPH, are Pfizer employees who have financial interests with Pfizer.

SAN ANTONIO – Prescription opioid abuse has continued declining since 2011, but opioids remain far more commonly abused than other prescription drugs, including gabapentin and pregabalin, new research shows.

“Both gabapentin and pregabalin are abused but at rates that are 6-56 times less frequent than for opioid analgesics,” wrote Kofi Asomaning, DSci, of Pfizer, and associates at Pfizer and Denver Health’s Rocky Mountain Poison and Drug Center.

“Gabapentin is generally more frequently abused than pregabalin,” they reported in a research poster at the annual meeting of the College on Problems of Drug Dependence.

The researchers analyzed data from the RADARS System Survey of Non-Medical Use of Prescription Drugs Program (NMURx), the RADARS System Treatment Center Programs Combined, and the American Association of Poison Control Centers National Poison Data System (NPDS).

All those use self-reported data. The first is a confidential, anonymous web-based survey used to estimate population-level prevalence, and the second surveys patients with opioid use disorder entering treatment. The NPDS tracks all cases reported to poison control centers nationally.


Analysis of the NMURx data revealed similar lifetime abuse prevalence rates for gabapentin and pregabalin at 0.4%, several magnitudes lower than the 5.3% rate identified with opioids.

Gabapentin, however, had higher rates of abuse in the past month in the Treatment Center Programs Combined. For the third to fourth quarter of 2017, 0.12 per 100,000 population reportedly abused gabapentin, compared with 0.01 per 100,000 for pregabalin. The rate for past-month abuse of opioids was 0.79 per 100,000.

A similar pattern for the same quarter emerged from the NPDS data: Rate of gabapentin abuse was 0.06 per 100,000, rate for pregabalin was 0.01 per 100,000, and rate for opioids was 0.40 per 100,000.

Both pregabalin and opioids were predominantly ingested, though a very small amount of each was inhaled and a similarly small amount of opioids was injected. Data on exposure route for gabapentin were not provided, though it was used more frequently than pregabalin.

The research was funded by Pfizer. The RADARS system is owned by Denver Health and Hospital Authority under the Colorado state government. RADARS receives some funding from pharmaceutical industry subscriptions. Dr. Asomaning and Diane L. Martire, MD, MPH, are Pfizer employees who have financial interests with Pfizer.

Adding the amyloid/tau/neurodegeneration (A/T/N) model of dementia to a clinical model may give an incremental but still significantly increased ability to predict cognitive decline over nearly 5 years, according to findings from a longitudinal cohort study of patients without dementia at baseline.

Courtesy Mayo Clinic

Although the A/T/N model is still intended only for research purposes, the study came to another important conclusion: About 50% of the memory change associated with normal aging was, in fact, caused by changes associated with Alzheimer’s disease, Clifford R. Jack Jr., MD, and colleagues wrote in JAMA.

The three groups with the fastest rates of memory decline all had abnormal amyloid and either abnormal tau and/or imaging signs of neurodegeneration. “This illustrated a dominant association of memory decline with amyloidosis but only when present in combination with tauopathy, neurodegeneration, or both,” Dr. Jack of the Mayo Clinic, Rochester, Minn., and coauthors wrote.

A/T/N, also known as the National Institute on Aging and Alzheimer’s Association Research Framework, is based on objective amyloid and tau biomarkers and imaging markers of neurodegeneration and is intended to more accurately differentiate Alzheimer’s from other dementias and, potentially, to stage the disease and predict and track decline. It generates eight clinical profiles that can identify Alzheimer’s, rule it out, or include it as a possible diagnosis.

The study comprised 480 elderly individuals enrolled in the Mayo Clinic Study on Aging. Median age of the participants ranged from 67 years in one of the eight clinical profiles (A–/T–/N–) to 83 years in another (A+/T+/N+). Most (92%) were cognitively normal; the remainder had mild cognitive impairment (MCI). They were followed for a median of 4.8 years.

Both amyloid and tau were measured with PET imaging; neuropathology was represented by MRI scans of cortical thickness. Most (n = 140) were negative for all biomarkers (A–/T–/N–). The group positive for all markers (A+/T+/N+) had the largest proportion of MCI subjects (30%). The apolipoprotein E epsilon 4 (APOE4) genotype was more common among the A+ groups than it was among the A– groups (40% vs. 21%).

The individual cognitive decline trajectories varied considerably by age and within each classification group. Only 7% of the A–/T–/N– group were 80 years or older, and only 2% of the A+/N+/T+ group were younger than 70 years.

In a clinical model, age and APOE4 status were significantly associated with faster rates of memory decline. Sex, education, and a cardiovascular/metabolic model were not, however.

“The estimated rate of memory decline in a 75-year-old individual who was an APOE4 noncarrier was –0.04 z-score units per year,” the authors wrote. “An 85-year-old individual who was also an APOE4 noncarrier could be expected to have a decline of –0.08 units per year, while a 75-year-old E4 carrier could be expected to have a decline of –0.08 units per year.”

Every 10 years of additional age was associated with a significant median worsening of 0.4 on z score for memory. A 4-year difference in education was associated with a 0.6-unit higher memory score, while APOE4 carriers had a 0.3-unit lower memory score.

The addition of the A/T/N model significantly improved the prediction of cognitive decline and memory score, although the rates of decline were still considerably variable. All of the A+ groups had the fastest decline rates.

“To place the predictive utility of biomarkers in clinical context, the decline in rates of memory for A+/T+/N–, A+/T–/N+, A+/T+/N+ [abnormal amyloid plus tau or neurodegeneration] were of similar magnitude to a 20-year increase in age and were twice that associated with APOE4 carriership,” they wrote.

A total of 88 participants had a second imaging visit at a median of 15 months. Most (n = 72) had no change in the A/T/N classification. A and T classifications were more stable (98% and 97%, respectively) than was N classification (84%).

A secondary analysis compared this model with generally accepted clinical and biomarker characteristics. Prior research has shown that prevalence of abnormal A/T/N biomarker groups increased with age in the Mayo Clinic Study on Aging. The mean annual memory z-score in this cohort at 60 years was 0.02, which dropped to 0.11 by age 90.

“Forty-six percent of this increase in decline rate [–0.06] was partitioned to the increasing prevalence of abnormal A/T/N profiles, while the remaining decline [–0.07] was partitioned to age,” the investigators reported.

While A+ subjects were most likely to decline, the A+/T–/N+ group presents a conundrum, the team wrote. “A possible explanation is that these individuals have early Alzheimer’s disease [denoted by A+T–] plus neurodegeneration due to comorbid non–Alzheimer’s disease neuropathic changes.”

This is an important point because the cognitive decline of Alzheimer’s is thought to be largely associated with tauopathy, not amyloidosis. “One possible explanation is an effect of subthreshold tau in A+/T–/N+ individuals, but this is speculative. Clearer understanding of the neuropathologic bases for the A+/T–/N+ group, as well as other A/T/N groups, awaits future biomarker-autopsy correlation studies.”

[email protected]

SOURCE: Jack CR et al. JAMA 2019;321:2316-25.

Adding the amyloid/tau/neurodegeneration (A/T/N) model of dementia to a clinical model may give an incremental but still significantly increased ability to predict cognitive decline over nearly 5 years, according to findings from a longitudinal cohort study of patients without dementia at baseline.

Courtesy Mayo Clinic

Although the A/T/N model is still intended only for research purposes, the study came to another important conclusion: About 50% of the memory change associated with normal aging was, in fact, caused by changes associated with Alzheimer’s disease, Clifford R. Jack Jr., MD, and colleagues wrote in JAMA.

The three groups with the fastest rates of memory decline all had abnormal amyloid and either abnormal tau and/or imaging signs of neurodegeneration. “This illustrated a dominant association of memory decline with amyloidosis but only when present in combination with tauopathy, neurodegeneration, or both,” Dr. Jack of the Mayo Clinic, Rochester, Minn., and coauthors wrote.

A/T/N, also known as the National Institute on Aging and Alzheimer’s Association Research Framework, is based on objective amyloid and tau biomarkers and imaging markers of neurodegeneration and is intended to more accurately differentiate Alzheimer’s from other dementias and, potentially, to stage the disease and predict and track decline. It generates eight clinical profiles that can identify Alzheimer’s, rule it out, or include it as a possible diagnosis.

The study comprised 480 elderly individuals enrolled in the Mayo Clinic Study on Aging. Median age of the participants ranged from 67 years in one of the eight clinical profiles (A–/T–/N–) to 83 years in another (A+/T+/N+). Most (92%) were cognitively normal; the remainder had mild cognitive impairment (MCI). They were followed for a median of 4.8 years.

Both amyloid and tau were measured with PET imaging; neuropathology was represented by MRI scans of cortical thickness. Most (n = 140) were negative for all biomarkers (A–/T–/N–). The group positive for all markers (A+/T+/N+) had the largest proportion of MCI subjects (30%). The apolipoprotein E epsilon 4 (APOE4) genotype was more common among the A+ groups than it was among the A– groups (40% vs. 21%).

The individual cognitive decline trajectories varied considerably by age and within each classification group. Only 7% of the A–/T–/N– group were 80 years or older, and only 2% of the A+/N+/T+ group were younger than 70 years.

In a clinical model, age and APOE4 status were significantly associated with faster rates of memory decline. Sex, education, and a cardiovascular/metabolic model were not, however.

“The estimated rate of memory decline in a 75-year-old individual who was an APOE4 noncarrier was –0.04 z-score units per year,” the authors wrote. “An 85-year-old individual who was also an APOE4 noncarrier could be expected to have a decline of –0.08 units per year, while a 75-year-old E4 carrier could be expected to have a decline of –0.08 units per year.”

Every 10 years of additional age was associated with a significant median worsening of 0.4 on z score for memory. A 4-year difference in education was associated with a 0.6-unit higher memory score, while APOE4 carriers had a 0.3-unit lower memory score.

The addition of the A/T/N model significantly improved the prediction of cognitive decline and memory score, although the rates of decline were still considerably variable. All of the A+ groups had the fastest decline rates.

“To place the predictive utility of biomarkers in clinical context, the decline in rates of memory for A+/T+/N–, A+/T–/N+, A+/T+/N+ [abnormal amyloid plus tau or neurodegeneration] were of similar magnitude to a 20-year increase in age and were twice that associated with APOE4 carriership,” they wrote.

A total of 88 participants had a second imaging visit at a median of 15 months. Most (n = 72) had no change in the A/T/N classification. A and T classifications were more stable (98% and 97%, respectively) than was N classification (84%).

A secondary analysis compared this model with generally accepted clinical and biomarker characteristics. Prior research has shown that prevalence of abnormal A/T/N biomarker groups increased with age in the Mayo Clinic Study on Aging. The mean annual memory z-score in this cohort at 60 years was 0.02, which dropped to 0.11 by age 90.

“Forty-six percent of this increase in decline rate [–0.06] was partitioned to the increasing prevalence of abnormal A/T/N profiles, while the remaining decline [–0.07] was partitioned to age,” the investigators reported.

While A+ subjects were most likely to decline, the A+/T–/N+ group presents a conundrum, the team wrote. “A possible explanation is that these individuals have early Alzheimer’s disease [denoted by A+T–] plus neurodegeneration due to comorbid non–Alzheimer’s disease neuropathic changes.”

This is an important point because the cognitive decline of Alzheimer’s is thought to be largely associated with tauopathy, not amyloidosis. “One possible explanation is an effect of subthreshold tau in A+/T–/N+ individuals, but this is speculative. Clearer understanding of the neuropathologic bases for the A+/T–/N+ group, as well as other A/T/N groups, awaits future biomarker-autopsy correlation studies.”

[email protected]

SOURCE: Jack CR et al. JAMA 2019;321:2316-25.

Adding the amyloid/tau/neurodegeneration (A/T/N) model of dementia to a clinical model may give an incremental but still significantly increased ability to predict cognitive decline over nearly 5 years, according to findings from a longitudinal cohort study of patients without dementia at baseline.

Courtesy Mayo Clinic

Although the A/T/N model is still intended only for research purposes, the study came to another important conclusion: About 50% of the memory change associated with normal aging was, in fact, caused by changes associated with Alzheimer’s disease, Clifford R. Jack Jr., MD, and colleagues wrote in JAMA.

The three groups with the fastest rates of memory decline all had abnormal amyloid and either abnormal tau and/or imaging signs of neurodegeneration. “This illustrated a dominant association of memory decline with amyloidosis but only when present in combination with tauopathy, neurodegeneration, or both,” Dr. Jack of the Mayo Clinic, Rochester, Minn., and coauthors wrote.

A/T/N, also known as the National Institute on Aging and Alzheimer’s Association Research Framework, is based on objective amyloid and tau biomarkers and imaging markers of neurodegeneration and is intended to more accurately differentiate Alzheimer’s from other dementias and, potentially, to stage the disease and predict and track decline. It generates eight clinical profiles that can identify Alzheimer’s, rule it out, or include it as a possible diagnosis.

The study comprised 480 elderly individuals enrolled in the Mayo Clinic Study on Aging. Median age of the participants ranged from 67 years in one of the eight clinical profiles (A–/T–/N–) to 83 years in another (A+/T+/N+). Most (92%) were cognitively normal; the remainder had mild cognitive impairment (MCI). They were followed for a median of 4.8 years.

Both amyloid and tau were measured with PET imaging; neuropathology was represented by MRI scans of cortical thickness. Most (n = 140) were negative for all biomarkers (A–/T–/N–). The group positive for all markers (A+/T+/N+) had the largest proportion of MCI subjects (30%). The apolipoprotein E epsilon 4 (APOE4) genotype was more common among the A+ groups than it was among the A– groups (40% vs. 21%).

The individual cognitive decline trajectories varied considerably by age and within each classification group. Only 7% of the A–/T–/N– group were 80 years or older, and only 2% of the A+/N+/T+ group were younger than 70 years.

In a clinical model, age and APOE4 status were significantly associated with faster rates of memory decline. Sex, education, and a cardiovascular/metabolic model were not, however.

“The estimated rate of memory decline in a 75-year-old individual who was an APOE4 noncarrier was –0.04 z-score units per year,” the authors wrote. “An 85-year-old individual who was also an APOE4 noncarrier could be expected to have a decline of –0.08 units per year, while a 75-year-old E4 carrier could be expected to have a decline of –0.08 units per year.”

Every 10 years of additional age was associated with a significant median worsening of 0.4 on z score for memory. A 4-year difference in education was associated with a 0.6-unit higher memory score, while APOE4 carriers had a 0.3-unit lower memory score.

The addition of the A/T/N model significantly improved the prediction of cognitive decline and memory score, although the rates of decline were still considerably variable. All of the A+ groups had the fastest decline rates.

“To place the predictive utility of biomarkers in clinical context, the decline in rates of memory for A+/T+/N–, A+/T–/N+, A+/T+/N+ [abnormal amyloid plus tau or neurodegeneration] were of similar magnitude to a 20-year increase in age and were twice that associated with APOE4 carriership,” they wrote.

A total of 88 participants had a second imaging visit at a median of 15 months. Most (n = 72) had no change in the A/T/N classification. A and T classifications were more stable (98% and 97%, respectively) than was N classification (84%).

A secondary analysis compared this model with generally accepted clinical and biomarker characteristics. Prior research has shown that prevalence of abnormal A/T/N biomarker groups increased with age in the Mayo Clinic Study on Aging. The mean annual memory z-score in this cohort at 60 years was 0.02, which dropped to 0.11 by age 90.

“Forty-six percent of this increase in decline rate [–0.06] was partitioned to the increasing prevalence of abnormal A/T/N profiles, while the remaining decline [–0.07] was partitioned to age,” the investigators reported.

While A+ subjects were most likely to decline, the A+/T–/N+ group presents a conundrum, the team wrote. “A possible explanation is that these individuals have early Alzheimer’s disease [denoted by A+T–] plus neurodegeneration due to comorbid non–Alzheimer’s disease neuropathic changes.”

This is an important point because the cognitive decline of Alzheimer’s is thought to be largely associated with tauopathy, not amyloidosis. “One possible explanation is an effect of subthreshold tau in A+/T–/N+ individuals, but this is speculative. Clearer understanding of the neuropathologic bases for the A+/T–/N+ group, as well as other A/T/N groups, awaits future biomarker-autopsy correlation studies.”

[email protected]

SOURCE: Jack CR et al. JAMA 2019;321:2316-25.

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

SEATTLE – Preliminary findings from a registry questionnaire reveal that 77% of patients with multiple sclerosis (MS) are employed either full or part time, with the rest being unemployed.

“MS seems to prevent people with MS from realizing their full potential at work or home,” said study coauthor Kottil Rammohan, MD, who summarized the study results in a video interview. Dr. Rammohan is professor of clinical neurology, director of the MS center of excellence, and chief of the multiple sclerosis division at the University of Miami. The study findings were presented at the annual meeting of the Consortium of Multiple Sclerosis Centers.

The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) prospectively collects information about the health care economics of patients with MS and its effects on daily life. In 2017, NARCRMS established the health care economics outcomes research (HEOR) advisory group. NARCRMS developed a Health-Related Productivity Questionnaire and Health Resource Utilization Questionnaire. The questionnaires were incorporated into the existing case report forms that are completed by patients at enrollment, annual, and exacerbation visits.

This analysis was based on 480 patients who had completed HEOR case report forms. Among those, 77% are employed either full or part time; however, of those 15% were underemployed, meaning they wanted to work more than their current work levels. About 13% are on disability.


“What we found was there was a significant impact at home as well,” said Dr. Rammohan. Patients reported that MS kept them from completing household chores. “MS is a disease that seems to impact not only the work environment, but also the home environment.”

When polled to determine the main reason why these MS patients are not able to function, “what we found was that it was not because of gait or immobility, it was difficulty related to fatigue,” Dr. Rammohan said. The second most common impairment was related to cognition.

“These are what we call the silent or the transparent symptoms of MS.”

Dr. Rammohan disclosed consulting fees from EMD Serono, Biogen, Sanofi-Aventis, Genzyme, Novartis, Teva Neurosciences, Acorda, and Roche/Genentech.

[email protected]

Cognitive decline accelerates in the long term after patients develop coronary heart disease (CHD), according to the results of a large prospective study with a median of 12 years of follow-up.

“We found that incident CHD was significantly associated with faster post–CHD-diagnosis cognitive decline, but not pre–CHD-diagnosis or short-term cognitive decline after the event,” Wuxiang Xie, PhD, of Peking University Health Science Center, Beijing, and associates wrote in the Journal of the American College of Cardiology. Linear mixed models showed that cognitive decline sped up during the year after incident CHD.

Past research had suggested a link between accelerated cognitive decline and CHD, but the temporal pattern of the relationship was unclear. For the study, Dr. Xie and associates followed 7,888 adults from the English Longitudinal Study of Aging who were an average of 62 years old and had no history of stroke, MI, angina, or dementia (Alzheimer’s disease or otherwise). All participants underwent a baseline cognitive assessment for verbal memory, semantic fluency, and temporal orientation, plus a median of six follow-up assessments.

In all, 480 (6%) participants developed CHD during follow-up. Their rate of cognitive decline remained constant before and immediately after their CHD diagnosis, but in subsequent years, they experienced significant accelerations in loss of global cognitive function, verbal memory, and temporal orientation even after accounting for time and many demographic and clinical variables. For example, the slope representing temporal change in global cognitive score decreased by a mean of 0.039 per year, compared with the pre-CHD slope (slope difference, –0.039; 95% confidence interval, –0.063 to –0.015; P =. 002). Semantic fluency also declined faster after CHD, but the difference, compared with before CHD, did not reach statistical significance (P = .11).

Individuals without CHD showed no such accelerations in cognitive decline throughout follow-up in adjusted models, the researchers wrote. “Based on repeated cognitive measurements over a long follow-up period, this study revealed a reliable and robust trajectory of cognitive decline [after CHD]. Future studies are warranted to determine the precise mechanisms linking incident CHD to cognitive decline.”

Funders included the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and the Newton International Fellowship from the Academy of Medical Sciences. The researchers reported having no relevant financial disclosures.

SOURCE: Xie W et al. J Amer Coll Cardiol. 2019 Jun 17. doi: 10.1016/j.jacc.2019.04.019.

Cognitive decline accelerates in the long term after patients develop coronary heart disease (CHD), according to the results of a large prospective study with a median of 12 years of follow-up.

“We found that incident CHD was significantly associated with faster post–CHD-diagnosis cognitive decline, but not pre–CHD-diagnosis or short-term cognitive decline after the event,” Wuxiang Xie, PhD, of Peking University Health Science Center, Beijing, and associates wrote in the Journal of the American College of Cardiology. Linear mixed models showed that cognitive decline sped up during the year after incident CHD.

Past research had suggested a link between accelerated cognitive decline and CHD, but the temporal pattern of the relationship was unclear. For the study, Dr. Xie and associates followed 7,888 adults from the English Longitudinal Study of Aging who were an average of 62 years old and had no history of stroke, MI, angina, or dementia (Alzheimer’s disease or otherwise). All participants underwent a baseline cognitive assessment for verbal memory, semantic fluency, and temporal orientation, plus a median of six follow-up assessments.

In all, 480 (6%) participants developed CHD during follow-up. Their rate of cognitive decline remained constant before and immediately after their CHD diagnosis, but in subsequent years, they experienced significant accelerations in loss of global cognitive function, verbal memory, and temporal orientation even after accounting for time and many demographic and clinical variables. For example, the slope representing temporal change in global cognitive score decreased by a mean of 0.039 per year, compared with the pre-CHD slope (slope difference, –0.039; 95% confidence interval, –0.063 to –0.015; P =. 002). Semantic fluency also declined faster after CHD, but the difference, compared with before CHD, did not reach statistical significance (P = .11).

Individuals without CHD showed no such accelerations in cognitive decline throughout follow-up in adjusted models, the researchers wrote. “Based on repeated cognitive measurements over a long follow-up period, this study revealed a reliable and robust trajectory of cognitive decline [after CHD]. Future studies are warranted to determine the precise mechanisms linking incident CHD to cognitive decline.”

Funders included the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and the Newton International Fellowship from the Academy of Medical Sciences. The researchers reported having no relevant financial disclosures.

SOURCE: Xie W et al. J Amer Coll Cardiol. 2019 Jun 17. doi: 10.1016/j.jacc.2019.04.019.

Cognitive decline accelerates in the long term after patients develop coronary heart disease (CHD), according to the results of a large prospective study with a median of 12 years of follow-up.

“We found that incident CHD was significantly associated with faster post–CHD-diagnosis cognitive decline, but not pre–CHD-diagnosis or short-term cognitive decline after the event,” Wuxiang Xie, PhD, of Peking University Health Science Center, Beijing, and associates wrote in the Journal of the American College of Cardiology. Linear mixed models showed that cognitive decline sped up during the year after incident CHD.

Past research had suggested a link between accelerated cognitive decline and CHD, but the temporal pattern of the relationship was unclear. For the study, Dr. Xie and associates followed 7,888 adults from the English Longitudinal Study of Aging who were an average of 62 years old and had no history of stroke, MI, angina, or dementia (Alzheimer’s disease or otherwise). All participants underwent a baseline cognitive assessment for verbal memory, semantic fluency, and temporal orientation, plus a median of six follow-up assessments.

In all, 480 (6%) participants developed CHD during follow-up. Their rate of cognitive decline remained constant before and immediately after their CHD diagnosis, but in subsequent years, they experienced significant accelerations in loss of global cognitive function, verbal memory, and temporal orientation even after accounting for time and many demographic and clinical variables. For example, the slope representing temporal change in global cognitive score decreased by a mean of 0.039 per year, compared with the pre-CHD slope (slope difference, –0.039; 95% confidence interval, –0.063 to –0.015; P =. 002). Semantic fluency also declined faster after CHD, but the difference, compared with before CHD, did not reach statistical significance (P = .11).

Individuals without CHD showed no such accelerations in cognitive decline throughout follow-up in adjusted models, the researchers wrote. “Based on repeated cognitive measurements over a long follow-up period, this study revealed a reliable and robust trajectory of cognitive decline [after CHD]. Future studies are warranted to determine the precise mechanisms linking incident CHD to cognitive decline.”

Funders included the National Natural Science Foundation of China, the Beijing Natural Science Foundation, and the Newton International Fellowship from the Academy of Medical Sciences. The researchers reported having no relevant financial disclosures.

SOURCE: Xie W et al. J Amer Coll Cardiol. 2019 Jun 17. doi: 10.1016/j.jacc.2019.04.019.

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

Patients with pediatric-onset multiple sclerosis are more likely than those with adult-onset disease to have impairment in information processing in adulthood, independent of age or disease duration, according to a study published in JAMA Neurology.

designer491/Thinkstock

Information-processing efficiency as measured by the Symbol Digit Modalities Test (SDMT) may decrease more rapidly in patients with pediatric-onset multiple sclerosis (MS).

“Children and adolescents who develop [MS] should be monitored closely for cognitive changes and helped to manage the potential challenges that early-onset multiple sclerosis poses for cognitive abilities later in life,” Kyla A. McKay, PhD, a researcher at Karolinska Institutet in Stockholm, and colleagues wrote.

Prior research has found that an SDMT score of 55 may be a point at which a person with MS is “employed but work challenged.” In the present study, patients with pediatric-onset MS reached this threshold at about age 34 years, whereas patients with adult-onset MS reached it at approximately 50 years. These findings suggest that the groups’ different cognitive outcomes “may be meaningful,” the researchers wrote.

Onset of MS before age 18 years occurs in 2%-10% of cases, but few studies have looked at cognitive outcomes of patients with pediatric-onset MS in adulthood. Cognitive impairment is common in patients with MS and may affect quality of life, social functioning, and employment.

To compare changes in cognitive function over time in adults with pediatric-onset MS versus adults with adult-onset MS, Dr. McKay and colleagues conducted a population-based, longitudinal cohort study using data from more than 5,700 patients in the Swedish Multiple Sclerosis Registry. The registry includes information from all neurology clinics in Sweden, and the researchers examined data collected between April 2006 and April 2018.

SDMT scores range from 0 to 120, and higher scores indicate greater information-processing efficiency.

The researchers classified patients with MS onset at younger than 18 years as pediatric-onset MS. The researchers excluded patients with fewer than two SDMT scores, patients younger than 18 years or older than 55 years at the time of testing, and patients with disease duration of 30 years or more.

The researchers included 5,704 patients, 300 of whom had pediatric-onset MS (5.3%). About 70% of the patients were female, and 98% had a relapsing-onset disease course. The pediatric-onset MS group had a younger median age at baseline than the adult-onset group did (26 years vs. 38 years). The patients had more than 46,000 SDMT scores, with an average baseline SDMT of 51; the median follow-up time was 3 years.

Patients with pediatric-onset MS had significantly lower SDMT scores (beta coefficient, –3.59), after adjusting for sex, age, disease duration, disease course, total number of SDMTs completed, oral or visual SDMT form, and exposure to disease-modifying therapy. Their scores also declined faster than those of patients with adult-onset MS (beta coefficient, –0.30; 95% confidence interval, –5.56 to –1.54), and they were more likely to ever have cognitive impairment (odds ratio, 1.44).

“At younger than 30 years, SDMT scores between the ... groups were comparable; but after 30 years of age the trajectories began to diverge,” Dr. McKay and associates wrote. At age 35 years, the mean SDMT score for patients with adult-onset MS was 61, whereas for patients with pediatric-onset MS it was 51. By age 40 years, the mean score was 58 for adult-onset MS versus 46 for pediatric-onset MS.

The study was supported by the Swedish Research Council and the Swedish Brain Foundation and by postdoctoral awards from the Canadian Institutes of Health Research to Dr. McKay and European Committee for Treatment and Research in Multiple Sclerosis to Dr. McKay. Coauthors reported receiving honoraria for speaking and serving on advisory boards for various pharmaceutical companies, as well as receiving research funding from agencies, foundations, and pharmaceutical companies.

[email protected]

SOURCE: McKay KA et al. JAMA Neurol. 2019 Jun 17. doi: 10.1001/jamaneurol.2019.1546.
 

SEATTLE – The one constant in multiple sclerosis (MS) is its lack of constancy. “As our lives are dynamic and change over time, MS is also dynamic and changes over time.” This is especially the case in women, noted Mitzi Joi Williams, MD.

bowdenimages/iStock/Getty Images

About three in four people with MS are female – about 750,000 in the United States. And the risk and incidence may be highest in African American women.

In a presentation about the unique needs of women with MS, Dr. Williams, an assistant professor of internal medicine at the Morehouse School of Medicine in Atlanta, offered these tips at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pay attention to sexual dysfunction

Patients with MS often are ashamed to talk about sexual dysfunction, Dr. Williams said, but it is on many minds. “If I have a program on intimacy in MS, people are out the door.”

She urged colleagues to understand that MS can affect sexuality through three routes: primary, secondary, and tertiary dysfunction.

In primary sexual dysfunction, brain and spinal lesions directly related to MS can cause problems such as lack of sensation or abnormal sensations, decreased libido, vaginal dryness, and difficult orgasm.

Secondary sexual dysfunction refers to problems caused by symptoms of MS such as fatigue, which can worsen as the day progresses and affect nighttime intimacy, she said. Bladder dysfunction is another sensitive area in sexuality, with patients – especially women – “concerned that they will lose control of their bladder or they have already lost control.”

Cognitive dysfunction also can disrupt sexual function. “It is important to focus, and certain things cannot happen if you do not. If you are not able to focus and concentrate, it can affect interest,” Dr. Williams said.

Additionally, medications can improve some symptoms while making others worse. For example, a drug may relieve spasticity but boost fatigue. “We have to walk this tightrope,” she said. “But if we are not asking our patients, they may not volunteer this information.”

Finally, she said, MS can spark tertiary sexual dysfunction – poor body image, depression, anxiety, and disruptive changes in familial roles. For example, one partner may become a caregiver, and “it is hard to go from caregiving to sexy time.”

“It is something we have to acknowledge and find ways to deal with,” Dr. Williams said.

To address these issues, she pointed to strategies for symptomatic relief and disease-modifying therapy (DMT) and pinpointed several treatment options.

• Fatigue – stimulants, diet, exercise.
• Spasticity – muscle relaxants, exercise.
• Bladder dysfunction – fluid restriction, medication.
• Paresthesia – antidepressants, anticonvulsants.
• Numbness – vibrators, devices to increase stimulation.

Sexual therapy, couples therapy, and pelvic floor physical therapy also can be helpful.

Be aware of special needs during prepregnancy and pregnancy

“MS itself does not have a lot of effects on fertility, pregnancy, or pregnancy outcomes,” Dr. Williams said. However, “medications cause concern about how we manage pregnancy and fertility.”

In vitro fertilization may increase the risk of relapse, she added, and patients on dimethyl fumarate who experience vomiting or diarrhea may not be able to properly absorb oral contraceptives.

Women with MS may not need to go off DMT when they are trying to conceive, she said. “If patients have very aggressive disease, they may need to be on DMT through conception, through the first trimester, and even the entire pregnancy to prevent long-term disability.”

What about pregnancy itself? “An MS diagnosis alone does not mean that a pregnancy is high risk,” she said. “There are not necessarily additional tests and ultrasounds that are recommended for our patients based on MS diagnosis alone.”

Treatment discontinuation may be warranted during pregnancy, when MS generally improves. However, some MS symptoms – fatigue, bladder dysfunction, and balance – may increase. Corticosteroids can be appropriate if relapses occur during pregnancy.

Menopause and MS symptoms may overlap

Symptoms such as hot flashes, mood changes, sleep disturbance, bladder dysfunction, and decreased energy may be signs of MS, or they could indicate menopause, Dr. Williams said. “Sometimes patients come in and they are getting worse, and we look into it and discover they are premenopausal.”

A decline in estrogen during menopause may worsen MS symptoms, she added, and hormone therapy may be appropriate. A phase 2 study found a benefit in menopausal patients with MS for estriol in conjunction with a DMT, but more studies are needed.

Dr. Williams reported no relevant financial disclosures.

SEATTLE – The one constant in multiple sclerosis (MS) is its lack of constancy. “As our lives are dynamic and change over time, MS is also dynamic and changes over time.” This is especially the case in women, noted Mitzi Joi Williams, MD.

bowdenimages/iStock/Getty Images

About three in four people with MS are female – about 750,000 in the United States. And the risk and incidence may be highest in African American women.

In a presentation about the unique needs of women with MS, Dr. Williams, an assistant professor of internal medicine at the Morehouse School of Medicine in Atlanta, offered these tips at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pay attention to sexual dysfunction

Patients with MS often are ashamed to talk about sexual dysfunction, Dr. Williams said, but it is on many minds. “If I have a program on intimacy in MS, people are out the door.”

She urged colleagues to understand that MS can affect sexuality through three routes: primary, secondary, and tertiary dysfunction.

In primary sexual dysfunction, brain and spinal lesions directly related to MS can cause problems such as lack of sensation or abnormal sensations, decreased libido, vaginal dryness, and difficult orgasm.

Secondary sexual dysfunction refers to problems caused by symptoms of MS such as fatigue, which can worsen as the day progresses and affect nighttime intimacy, she said. Bladder dysfunction is another sensitive area in sexuality, with patients – especially women – “concerned that they will lose control of their bladder or they have already lost control.”

Cognitive dysfunction also can disrupt sexual function. “It is important to focus, and certain things cannot happen if you do not. If you are not able to focus and concentrate, it can affect interest,” Dr. Williams said.

Additionally, medications can improve some symptoms while making others worse. For example, a drug may relieve spasticity but boost fatigue. “We have to walk this tightrope,” she said. “But if we are not asking our patients, they may not volunteer this information.”

Finally, she said, MS can spark tertiary sexual dysfunction – poor body image, depression, anxiety, and disruptive changes in familial roles. For example, one partner may become a caregiver, and “it is hard to go from caregiving to sexy time.”

“It is something we have to acknowledge and find ways to deal with,” Dr. Williams said.

To address these issues, she pointed to strategies for symptomatic relief and disease-modifying therapy (DMT) and pinpointed several treatment options.

• Fatigue – stimulants, diet, exercise.
• Spasticity – muscle relaxants, exercise.
• Bladder dysfunction – fluid restriction, medication.
• Paresthesia – antidepressants, anticonvulsants.
• Numbness – vibrators, devices to increase stimulation.

Sexual therapy, couples therapy, and pelvic floor physical therapy also can be helpful.

Be aware of special needs during prepregnancy and pregnancy

“MS itself does not have a lot of effects on fertility, pregnancy, or pregnancy outcomes,” Dr. Williams said. However, “medications cause concern about how we manage pregnancy and fertility.”

In vitro fertilization may increase the risk of relapse, she added, and patients on dimethyl fumarate who experience vomiting or diarrhea may not be able to properly absorb oral contraceptives.

Women with MS may not need to go off DMT when they are trying to conceive, she said. “If patients have very aggressive disease, they may need to be on DMT through conception, through the first trimester, and even the entire pregnancy to prevent long-term disability.”

What about pregnancy itself? “An MS diagnosis alone does not mean that a pregnancy is high risk,” she said. “There are not necessarily additional tests and ultrasounds that are recommended for our patients based on MS diagnosis alone.”

Treatment discontinuation may be warranted during pregnancy, when MS generally improves. However, some MS symptoms – fatigue, bladder dysfunction, and balance – may increase. Corticosteroids can be appropriate if relapses occur during pregnancy.

Menopause and MS symptoms may overlap

Symptoms such as hot flashes, mood changes, sleep disturbance, bladder dysfunction, and decreased energy may be signs of MS, or they could indicate menopause, Dr. Williams said. “Sometimes patients come in and they are getting worse, and we look into it and discover they are premenopausal.”

A decline in estrogen during menopause may worsen MS symptoms, she added, and hormone therapy may be appropriate. A phase 2 study found a benefit in menopausal patients with MS for estriol in conjunction with a DMT, but more studies are needed.

Dr. Williams reported no relevant financial disclosures.

SEATTLE – The one constant in multiple sclerosis (MS) is its lack of constancy. “As our lives are dynamic and change over time, MS is also dynamic and changes over time.” This is especially the case in women, noted Mitzi Joi Williams, MD.

bowdenimages/iStock/Getty Images

About three in four people with MS are female – about 750,000 in the United States. And the risk and incidence may be highest in African American women.

In a presentation about the unique needs of women with MS, Dr. Williams, an assistant professor of internal medicine at the Morehouse School of Medicine in Atlanta, offered these tips at the annual meeting of the Consortium of Multiple Sclerosis Centers.

Pay attention to sexual dysfunction

Patients with MS often are ashamed to talk about sexual dysfunction, Dr. Williams said, but it is on many minds. “If I have a program on intimacy in MS, people are out the door.”

She urged colleagues to understand that MS can affect sexuality through three routes: primary, secondary, and tertiary dysfunction.

In primary sexual dysfunction, brain and spinal lesions directly related to MS can cause problems such as lack of sensation or abnormal sensations, decreased libido, vaginal dryness, and difficult orgasm.

Secondary sexual dysfunction refers to problems caused by symptoms of MS such as fatigue, which can worsen as the day progresses and affect nighttime intimacy, she said. Bladder dysfunction is another sensitive area in sexuality, with patients – especially women – “concerned that they will lose control of their bladder or they have already lost control.”

Cognitive dysfunction also can disrupt sexual function. “It is important to focus, and certain things cannot happen if you do not. If you are not able to focus and concentrate, it can affect interest,” Dr. Williams said.

Additionally, medications can improve some symptoms while making others worse. For example, a drug may relieve spasticity but boost fatigue. “We have to walk this tightrope,” she said. “But if we are not asking our patients, they may not volunteer this information.”

Finally, she said, MS can spark tertiary sexual dysfunction – poor body image, depression, anxiety, and disruptive changes in familial roles. For example, one partner may become a caregiver, and “it is hard to go from caregiving to sexy time.”

“It is something we have to acknowledge and find ways to deal with,” Dr. Williams said.

To address these issues, she pointed to strategies for symptomatic relief and disease-modifying therapy (DMT) and pinpointed several treatment options.

• Fatigue – stimulants, diet, exercise.
• Spasticity – muscle relaxants, exercise.
• Bladder dysfunction – fluid restriction, medication.
• Paresthesia – antidepressants, anticonvulsants.
• Numbness – vibrators, devices to increase stimulation.

Sexual therapy, couples therapy, and pelvic floor physical therapy also can be helpful.

Be aware of special needs during prepregnancy and pregnancy

“MS itself does not have a lot of effects on fertility, pregnancy, or pregnancy outcomes,” Dr. Williams said. However, “medications cause concern about how we manage pregnancy and fertility.”

In vitro fertilization may increase the risk of relapse, she added, and patients on dimethyl fumarate who experience vomiting or diarrhea may not be able to properly absorb oral contraceptives.

Women with MS may not need to go off DMT when they are trying to conceive, she said. “If patients have very aggressive disease, they may need to be on DMT through conception, through the first trimester, and even the entire pregnancy to prevent long-term disability.”

What about pregnancy itself? “An MS diagnosis alone does not mean that a pregnancy is high risk,” she said. “There are not necessarily additional tests and ultrasounds that are recommended for our patients based on MS diagnosis alone.”

Treatment discontinuation may be warranted during pregnancy, when MS generally improves. However, some MS symptoms – fatigue, bladder dysfunction, and balance – may increase. Corticosteroids can be appropriate if relapses occur during pregnancy.

Menopause and MS symptoms may overlap

Symptoms such as hot flashes, mood changes, sleep disturbance, bladder dysfunction, and decreased energy may be signs of MS, or they could indicate menopause, Dr. Williams said. “Sometimes patients come in and they are getting worse, and we look into it and discover they are premenopausal.”

A decline in estrogen during menopause may worsen MS symptoms, she added, and hormone therapy may be appropriate. A phase 2 study found a benefit in menopausal patients with MS for estriol in conjunction with a DMT, but more studies are needed.

Dr. Williams reported no relevant financial disclosures.

The other day, I saw a patient who really brought home the importance of considering culture in psychiatry. The patient’s chief complaint was that he had been hearing the voice of an “invisible man.” I noticed he had an accent I was familiar with, and it sounded like he was from Haiti. Indeed, he was born there.

Accordingly, I asked him about voodoo. He said he is not a voodoo worshiper but he believes in voodoo – and he thought that that was what was happening to him. He reported this was the second time he heard the voices – the last time was less than a year ago. He said he came to the hospital because he was trying to wash dishes when he felt some invisible force holding him down. The patient got upset, and he broke the dishes he was washing. Of course, a big melee ensued, and the police were called. They brought the patient to my hospital.

When I spoke with him, he said he was doing pretty well with his Parkinson’s disease but he was a little stiff. The patient was on carbidopa-levodopa 25-100 mg 1.5 t.i.d. for his Parkinson’s, quetiapine 50 mg b.i.d. for his psychotic symptoms, amantadine 100 mg b.i.d. to stimulate his dopamine, ropinirole 1 mg t.i.d. for restless legs, and baclofen 10 mg t.i.d. for muscle spasms.

This is a 66-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic, and he had a wide range of affect as he was able to smile, get serious, and be sad (about his problems). His speech was relevant, linear, and goal directed. His thought processes did not show any signs of loose associations, tangentiality or circumstantiality, but he did have delusions, and current auditory and visual hallucinations. His thought content was surrounding his problems, which because of the culture he is from, were attributed by him to voodoo. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was average. Despite my explaining to him that his psychotic symptoms were caused by the medication he was taking, his judgment and insight were fair as he explained to me the things that were happening to him were so tangible they had to be real. He had no suicidal or homicidal ideation.

I decided to leave his meds as is, and I gave him 25 mg loxapine at h.s.

When I saw him a few days later, I asked him how he was doing, and he reported that the invisible man and all of his shenanigans were gone. I again explained that the medication he was taking for his Parkinson’s was causing his psychotic symptoms, and now I had proof. Had the voices been tied to voodoo, the medication would not have stopped the symptoms. He looked skeptical.

This struck me as a perfect example of the importance of culture in psychiatry, and I thought it instructive to share.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of the Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), all in Chicago. He is recipient of the American Psychiatric Association’s 2019 Adolph Meyer Award for Lifetime Achievement in Psychiatric Research. Check out Dr. Bell’s new book, Fetal Alcohol Exposure in the African-American Community, at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community.

The other day, I saw a patient who really brought home the importance of considering culture in psychiatry. The patient’s chief complaint was that he had been hearing the voice of an “invisible man.” I noticed he had an accent I was familiar with, and it sounded like he was from Haiti. Indeed, he was born there.

Accordingly, I asked him about voodoo. He said he is not a voodoo worshiper but he believes in voodoo – and he thought that that was what was happening to him. He reported this was the second time he heard the voices – the last time was less than a year ago. He said he came to the hospital because he was trying to wash dishes when he felt some invisible force holding him down. The patient got upset, and he broke the dishes he was washing. Of course, a big melee ensued, and the police were called. They brought the patient to my hospital.

When I spoke with him, he said he was doing pretty well with his Parkinson’s disease but he was a little stiff. The patient was on carbidopa-levodopa 25-100 mg 1.5 t.i.d. for his Parkinson’s, quetiapine 50 mg b.i.d. for his psychotic symptoms, amantadine 100 mg b.i.d. to stimulate his dopamine, ropinirole 1 mg t.i.d. for restless legs, and baclofen 10 mg t.i.d. for muscle spasms.

This is a 66-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic, and he had a wide range of affect as he was able to smile, get serious, and be sad (about his problems). His speech was relevant, linear, and goal directed. His thought processes did not show any signs of loose associations, tangentiality or circumstantiality, but he did have delusions, and current auditory and visual hallucinations. His thought content was surrounding his problems, which because of the culture he is from, were attributed by him to voodoo. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was average. Despite my explaining to him that his psychotic symptoms were caused by the medication he was taking, his judgment and insight were fair as he explained to me the things that were happening to him were so tangible they had to be real. He had no suicidal or homicidal ideation.

I decided to leave his meds as is, and I gave him 25 mg loxapine at h.s.

When I saw him a few days later, I asked him how he was doing, and he reported that the invisible man and all of his shenanigans were gone. I again explained that the medication he was taking for his Parkinson’s was causing his psychotic symptoms, and now I had proof. Had the voices been tied to voodoo, the medication would not have stopped the symptoms. He looked skeptical.

This struck me as a perfect example of the importance of culture in psychiatry, and I thought it instructive to share.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of the Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), all in Chicago. He is recipient of the American Psychiatric Association’s 2019 Adolph Meyer Award for Lifetime Achievement in Psychiatric Research. Check out Dr. Bell’s new book, Fetal Alcohol Exposure in the African-American Community, at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community.

The other day, I saw a patient who really brought home the importance of considering culture in psychiatry. The patient’s chief complaint was that he had been hearing the voice of an “invisible man.” I noticed he had an accent I was familiar with, and it sounded like he was from Haiti. Indeed, he was born there.

Accordingly, I asked him about voodoo. He said he is not a voodoo worshiper but he believes in voodoo – and he thought that that was what was happening to him. He reported this was the second time he heard the voices – the last time was less than a year ago. He said he came to the hospital because he was trying to wash dishes when he felt some invisible force holding him down. The patient got upset, and he broke the dishes he was washing. Of course, a big melee ensued, and the police were called. They brought the patient to my hospital.

When I spoke with him, he said he was doing pretty well with his Parkinson’s disease but he was a little stiff. The patient was on carbidopa-levodopa 25-100 mg 1.5 t.i.d. for his Parkinson’s, quetiapine 50 mg b.i.d. for his psychotic symptoms, amantadine 100 mg b.i.d. to stimulate his dopamine, ropinirole 1 mg t.i.d. for restless legs, and baclofen 10 mg t.i.d. for muscle spasms.

This is a 66-year-old male who was appropriately groomed and who was cooperative with the interview. He was not hyperactive or lethargic. His mood was euthymic, and he had a wide range of affect as he was able to smile, get serious, and be sad (about his problems). His speech was relevant, linear, and goal directed. His thought processes did not show any signs of loose associations, tangentiality or circumstantiality, but he did have delusions, and current auditory and visual hallucinations. His thought content was surrounding his problems, which because of the culture he is from, were attributed by him to voodoo. He was attentive, and his recent and remote memory were intact. Clinical estimate of his intelligence was average. Despite my explaining to him that his psychotic symptoms were caused by the medication he was taking, his judgment and insight were fair as he explained to me the things that were happening to him were so tangible they had to be real. He had no suicidal or homicidal ideation.

I decided to leave his meds as is, and I gave him 25 mg loxapine at h.s.

When I saw him a few days later, I asked him how he was doing, and he reported that the invisible man and all of his shenanigans were gone. I again explained that the medication he was taking for his Parkinson’s was causing his psychotic symptoms, and now I had proof. Had the voices been tied to voodoo, the medication would not have stopped the symptoms. He looked skeptical.

This struck me as a perfect example of the importance of culture in psychiatry, and I thought it instructive to share.

Dr. Bell is a staff psychiatrist at Jackson Park Hospital’s Medical/Surgical-Psychiatry Inpatient Unit; clinical psychiatrist emeritus in the department of psychiatry at the University of Illinois at Chicago; former president/CEO of the Community Mental Health Council; and former director of the Institute for Juvenile Research (birthplace of child psychiatry), all in Chicago. He is recipient of the American Psychiatric Association’s 2019 Adolph Meyer Award for Lifetime Achievement in Psychiatric Research. Check out Dr. Bell’s new book, Fetal Alcohol Exposure in the African-American Community, at https://thirdworldpressfoundation.org/product/pre-order-fetal-alcohol-exposure-in-the-african-american-community.

PHILADELPHIA – Mutant huntingtin and neurofilament light are valid potential biomarkers in Huntington’s disease and could be used in future clinical trials, according to an investigation presented at the annual meeting of the American Academy of Neurology. These biomarkers appear to reflect the earliest detectable changes in the natural history of Huntington’s disease, but the longitudinal prognostic value of changes in these biomarkers requires further investigation, the researchers said.

Huntington’s disease has a long prodromal phase and is associated with long survival. Investigators still need well-validated biomarkers of disease progression, prognosis, and pharmacodynamics to aid drug development, said Filipe B. Rodrigues, MD, clinical research fellow at University College London. After several years of study, Dr. Rodrigues and colleagues found mutant huntingtin and neurofilament light (NfL) to be the most promising potential biomarkers in Huntington’s disease. They sought to understand how these two biomarkers compare with each other, what their predictive ability is, and how they change longitudinally.

To this end, Dr. Rodrigues and colleagues designed the HD-CSF study, a prospective, observational, longitudinal cohort study with a 2-year follow-up. They recruited 20 healthy controls, 20 patients with premanifest Huntington’s disease, and 40 patients with manifest Huntington’s disease. All participants underwent regular clinical assessments and standardized collections of cerebrospinal fluid (CSF) and blood. They also had the option of undergoing brain MRI scans.

The investigators analyzed their data using multiple linear regression models, Pearson’s correlations, receiver operating characteristic curves, and sample size calculations. They used an event-based model to evaluate the temporal sequence of changes in Huntington’s disease-related biomarkers.

Dr. Rodrigues and colleagues first observed that all three biomarkers successfully distinguished between healthy controls, patients with premanifest Huntington’s disease, and patients with Huntington’s disease. Mutant huntingtin, the pathogenic agent in Huntington’s disease, discriminated perfectly between healthy controls and mutation carriers, as the researchers had expected. CSF and plasma levels of NfL also discriminated well between healthy controls and mutation carriers. These biomarkers had areas under the ROC curve greater than 0.9. NfL in plasma and CSF also distinguished well between patients with premanifest Huntington’s disease and those with manifest Huntington’s disease, with areas under the curve greater than 0.9. Their discriminative ability in this regard was significantly better than that of mutant huntingtin.

When the researchers examined the relationship between the three biomarkers, they found that CSF levels of NfL were strongly correlated in a linear fashion with plasma levels of NfL. CSF levels of mutant huntingtin were moderately associated with CSF levels of NfL.

Levels of all three biomarkers increased significantly as the disease progressed and were associated with all clinical scales and imaging measures. CSF and plasma levels of NfL had superior predictive ability for clinical and imaging measures, compared with mutant huntingtin. CSF and plasma NfL were associated with brain volume, but mutant huntingtin was not.

All three biomarkers were stable during a 6-week period. Dr. Rodrigues and colleagues calculated sample sizes for a two-arm interventional trial involving various hypothetical therapeutic effects. They found that the required sample sizes were small enough to be incorporated easily into ongoing and future clinical trials.

In silico modeling suggested among the markers measured in the HD-CSF study, the three biofluid biomarkers were the first factors to be altered in the course of Huntington’s disease. Alterations in the biomarkers were followed by changes in imaging markers, and then by changes in clinical markers (for example, motor and cognitive function).

Finally, Dr. Rodrigues and colleagues found preliminary evidence that levels of NfL in CSF and plasma increase over time at different rates in patients with Huntington’s disease, compared with healthy controls. NfL appears to be more useful than mutant huntingtin for evaluating the rate of disease progression than for gauging response to treatment, said Dr. Rodrigues. “If [we] can prove that we can assess response to treatment by measuring NfL, I think that would be great.”

The investigators are currently analyzing the longitudinal predictive value of changes in these biomarkers. They also have begun analyzing other markers such as tau and brain-derived neurotrophic factor.

This study was funded by the Medical Research Council UK, the CHDI Foundation, and F. Hoffmann-La Roche.
 

This article was updated 6/18/19.

[email protected]

SOURCE: Rodrigues FB et al. AAN 2019, Abstract S16.003.

PHILADELPHIA – Mutant huntingtin and neurofilament light are valid potential biomarkers in Huntington’s disease and could be used in future clinical trials, according to an investigation presented at the annual meeting of the American Academy of Neurology. These biomarkers appear to reflect the earliest detectable changes in the natural history of Huntington’s disease, but the longitudinal prognostic value of changes in these biomarkers requires further investigation, the researchers said.

Huntington’s disease has a long prodromal phase and is associated with long survival. Investigators still need well-validated biomarkers of disease progression, prognosis, and pharmacodynamics to aid drug development, said Filipe B. Rodrigues, MD, clinical research fellow at University College London. After several years of study, Dr. Rodrigues and colleagues found mutant huntingtin and neurofilament light (NfL) to be the most promising potential biomarkers in Huntington’s disease. They sought to understand how these two biomarkers compare with each other, what their predictive ability is, and how they change longitudinally.

To this end, Dr. Rodrigues and colleagues designed the HD-CSF study, a prospective, observational, longitudinal cohort study with a 2-year follow-up. They recruited 20 healthy controls, 20 patients with premanifest Huntington’s disease, and 40 patients with manifest Huntington’s disease. All participants underwent regular clinical assessments and standardized collections of cerebrospinal fluid (CSF) and blood. They also had the option of undergoing brain MRI scans.

The investigators analyzed their data using multiple linear regression models, Pearson’s correlations, receiver operating characteristic curves, and sample size calculations. They used an event-based model to evaluate the temporal sequence of changes in Huntington’s disease-related biomarkers.

Dr. Rodrigues and colleagues first observed that all three biomarkers successfully distinguished between healthy controls, patients with premanifest Huntington’s disease, and patients with Huntington’s disease. Mutant huntingtin, the pathogenic agent in Huntington’s disease, discriminated perfectly between healthy controls and mutation carriers, as the researchers had expected. CSF and plasma levels of NfL also discriminated well between healthy controls and mutation carriers. These biomarkers had areas under the ROC curve greater than 0.9. NfL in plasma and CSF also distinguished well between patients with premanifest Huntington’s disease and those with manifest Huntington’s disease, with areas under the curve greater than 0.9. Their discriminative ability in this regard was significantly better than that of mutant huntingtin.

When the researchers examined the relationship between the three biomarkers, they found that CSF levels of NfL were strongly correlated in a linear fashion with plasma levels of NfL. CSF levels of mutant huntingtin were moderately associated with CSF levels of NfL.

Levels of all three biomarkers increased significantly as the disease progressed and were associated with all clinical scales and imaging measures. CSF and plasma levels of NfL had superior predictive ability for clinical and imaging measures, compared with mutant huntingtin. CSF and plasma NfL were associated with brain volume, but mutant huntingtin was not.

All three biomarkers were stable during a 6-week period. Dr. Rodrigues and colleagues calculated sample sizes for a two-arm interventional trial involving various hypothetical therapeutic effects. They found that the required sample sizes were small enough to be incorporated easily into ongoing and future clinical trials.

In silico modeling suggested among the markers measured in the HD-CSF study, the three biofluid biomarkers were the first factors to be altered in the course of Huntington’s disease. Alterations in the biomarkers were followed by changes in imaging markers, and then by changes in clinical markers (for example, motor and cognitive function).

Finally, Dr. Rodrigues and colleagues found preliminary evidence that levels of NfL in CSF and plasma increase over time at different rates in patients with Huntington’s disease, compared with healthy controls. NfL appears to be more useful than mutant huntingtin for evaluating the rate of disease progression than for gauging response to treatment, said Dr. Rodrigues. “If [we] can prove that we can assess response to treatment by measuring NfL, I think that would be great.”

The investigators are currently analyzing the longitudinal predictive value of changes in these biomarkers. They also have begun analyzing other markers such as tau and brain-derived neurotrophic factor.

This study was funded by the Medical Research Council UK, the CHDI Foundation, and F. Hoffmann-La Roche.
 

This article was updated 6/18/19.

[email protected]

SOURCE: Rodrigues FB et al. AAN 2019, Abstract S16.003.

PHILADELPHIA – Mutant huntingtin and neurofilament light are valid potential biomarkers in Huntington’s disease and could be used in future clinical trials, according to an investigation presented at the annual meeting of the American Academy of Neurology. These biomarkers appear to reflect the earliest detectable changes in the natural history of Huntington’s disease, but the longitudinal prognostic value of changes in these biomarkers requires further investigation, the researchers said.

Huntington’s disease has a long prodromal phase and is associated with long survival. Investigators still need well-validated biomarkers of disease progression, prognosis, and pharmacodynamics to aid drug development, said Filipe B. Rodrigues, MD, clinical research fellow at University College London. After several years of study, Dr. Rodrigues and colleagues found mutant huntingtin and neurofilament light (NfL) to be the most promising potential biomarkers in Huntington’s disease. They sought to understand how these two biomarkers compare with each other, what their predictive ability is, and how they change longitudinally.

To this end, Dr. Rodrigues and colleagues designed the HD-CSF study, a prospective, observational, longitudinal cohort study with a 2-year follow-up. They recruited 20 healthy controls, 20 patients with premanifest Huntington’s disease, and 40 patients with manifest Huntington’s disease. All participants underwent regular clinical assessments and standardized collections of cerebrospinal fluid (CSF) and blood. They also had the option of undergoing brain MRI scans.

The investigators analyzed their data using multiple linear regression models, Pearson’s correlations, receiver operating characteristic curves, and sample size calculations. They used an event-based model to evaluate the temporal sequence of changes in Huntington’s disease-related biomarkers.

Dr. Rodrigues and colleagues first observed that all three biomarkers successfully distinguished between healthy controls, patients with premanifest Huntington’s disease, and patients with Huntington’s disease. Mutant huntingtin, the pathogenic agent in Huntington’s disease, discriminated perfectly between healthy controls and mutation carriers, as the researchers had expected. CSF and plasma levels of NfL also discriminated well between healthy controls and mutation carriers. These biomarkers had areas under the ROC curve greater than 0.9. NfL in plasma and CSF also distinguished well between patients with premanifest Huntington’s disease and those with manifest Huntington’s disease, with areas under the curve greater than 0.9. Their discriminative ability in this regard was significantly better than that of mutant huntingtin.

When the researchers examined the relationship between the three biomarkers, they found that CSF levels of NfL were strongly correlated in a linear fashion with plasma levels of NfL. CSF levels of mutant huntingtin were moderately associated with CSF levels of NfL.

Levels of all three biomarkers increased significantly as the disease progressed and were associated with all clinical scales and imaging measures. CSF and plasma levels of NfL had superior predictive ability for clinical and imaging measures, compared with mutant huntingtin. CSF and plasma NfL were associated with brain volume, but mutant huntingtin was not.

All three biomarkers were stable during a 6-week period. Dr. Rodrigues and colleagues calculated sample sizes for a two-arm interventional trial involving various hypothetical therapeutic effects. They found that the required sample sizes were small enough to be incorporated easily into ongoing and future clinical trials.

In silico modeling suggested among the markers measured in the HD-CSF study, the three biofluid biomarkers were the first factors to be altered in the course of Huntington’s disease. Alterations in the biomarkers were followed by changes in imaging markers, and then by changes in clinical markers (for example, motor and cognitive function).

Finally, Dr. Rodrigues and colleagues found preliminary evidence that levels of NfL in CSF and plasma increase over time at different rates in patients with Huntington’s disease, compared with healthy controls. NfL appears to be more useful than mutant huntingtin for evaluating the rate of disease progression than for gauging response to treatment, said Dr. Rodrigues. “If [we] can prove that we can assess response to treatment by measuring NfL, I think that would be great.”

The investigators are currently analyzing the longitudinal predictive value of changes in these biomarkers. They also have begun analyzing other markers such as tau and brain-derived neurotrophic factor.

This study was funded by the Medical Research Council UK, the CHDI Foundation, and F. Hoffmann-La Roche.
 

This article was updated 6/18/19.

[email protected]

SOURCE: Rodrigues FB et al. AAN 2019, Abstract S16.003.