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Neurology News

Follow our Neurology News blog for the latest news on neurologic diseases and research.

Thursday, April 18, 2019

Mindfulness yoga for patients with mild-to-moderate Parkinson's disease (PD) appeared to be as effective and safe as stretching and resistance training exercise in improving motor function and mobility, according to a randomized clinical trial published online on April 8 in JAMA Neurology.

However, patients who did yoga experienced a greater reduction in anxiety and depressive symptoms and an increase in spiritual well-being and health-related quality of life, or how they perceived physical and mental health over time.

"These findings suggest that mindfulness yoga is an effective treatment option for patients with PD to manage stress and symptoms," the researchers, led by Jojo Y. Y. Kwok, PhD, a research assistant professor of nursing at the University of Hong Kong, wrote. "Considering that PD is not only a physically limiting condition but also a psychologically distressing life event, health care professionals should adopt a holistic approach in PD rehabilitation."

In the study, the researchers included 138 adults with idiopathic PD (average age 63.7 years; 47.1 percent men) who were able to stand on their own and walk with or without an assistive device. Participants were randomly assigned to eight weeks of either a mindfulness yoga program or an exercise program that focused on stretching and resistance training to improve mobility and stability. The trial was conducted at four community rehabilitation centers in Hong Kong between December 2016 and May 2017.

Participants in the stretching and resistance training group had one weekly 60-minute group session. They were also encouraged to perform 20-minute home-based practice twice of week. The protocol of this group consisted of a progressive set of warm-up, resistance training and stretching, and cool-down exercises, which were reviewed by two physiotherapists to confirm validity for PD patients.

The yoga group had one weekly 90-minute session of Hatha yoga, which is the practice of physical yoga poses with a focus on breathing and meditation. The session includes 12 basic Hatha yoga poses: sun salutations (60 minutes) with controlled breathing (15 minutes) and mindfulness meditation (15 minutes). They were also told to practice at home for 20 minutes twice a week.

Researchers assessed anxiety and depressive symptoms using a self-report questionnaire that consists of anxiety and depression subscales with a high score representing a high level of psychological distress. Motor symptom severity, mobility, spiritual well-being, and health-related quality of life were also measured.

The researchers assessed patients at baseline, eight weeks, and 20 weeks.

Participants in the yoga group had significantly better improvement in outcomes than the stretching and resistance training exercise group, including anxiety (time-by-group interaction, beta, –1.79 at 8 weeks; –2.05 at 20 weeks) and depressive symptoms (beta, –2.75 at 8 weeks; –2.75 at 20 weeks).

No significant improvements in anxiety or depressive symptoms were found in the stretching and resistance training group at the different assessments.

The yoga group fared better in disease-specific health-related quality of life (beta, –7.77 at 8 weeks; –7.99 at 20 weeks) and in perceived hardship (beta, -0.92 at 8 weeks; 0.76 at 20 weeks), compared with the stretching and resistance training group.

The researchers noted that the benefits were noted after only six sessions of the yoga-mindfulness training.

Both groups experienced reductions in motor symptoms, which were significantly higher among the stretching and resistance training group, but the differences in average scores between the two groups were clinically insignificant, according to the researchers.

A total of three participants in the yoga group and two in the control group reported temporary mild knee pain.

Study limitations included expectation bias due to the possibility participants were aware of the treatment they were assigned; selection bias because participants were enrolled through convenience sampling, and lastly, the dropout rates were 15.2 percent at eight weeks and 18.8 percent at 20 weeks.

The Professional Development Fund of the Association of Hong Kong Nursing Staff supported the trial. The authors reported no relevant disclosures.

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Kwok JYY, Kwan JCY, Auyeung M, et al. Effects of mindfulness yoga vs stretching and resistance training exercises on anxiety and depression for people with Parkinson disease: A randomized clinical trial. JAMA Neurol 2019; Epub 2019 Apr 8.

Tuesday, April 16, 2019

PET scans revealed elevated levels of abnormal tau protein in areas affected by chronic traumatic encephalopathy in living former National Football League (NFL) players with cognitive, mood, and behavioral symptoms, according to a study published online on April 10 in the New England Journal of Medicine (NEJM).

Flortaucipir PET imaging showed higher amounts of tau in the bilateral superior frontal, bilateral medial temporal, and left parietal regions in the former NFL players, compared with asymptomatic controls with no history of traumatic brain injury (TBI).

However, the researchers, led by Robert Stern, PhD, professor of neurology, neurosurgery and anatomy and neurobiology at Boston University School of Medicine , noted they found no relationship between tau PET levels and cognitive test performance or severity of mood and behavioral symptoms.

"Although persons with the neuropathologic features of CTE have been reported to have cognitive impairment, mood disturbance, and behavioral dyscontrol, it is unclear whether these features are associated with regional tau deposition, tau-related neuronal degeneration, or other consequences of brain trauma," they wrote.

The researchers stressed that the PET scan is not ready for clinical use. The greatest advance is in helping researchers learn more about the pathophysiology of CTE, they said.

CTE is a neurodegenerative disease associated with repetitive head impacts. CTE diagnosis is pathologically defined by a specific pattern of tau deposition with little amyloid-beta deposition that differs from other disorders, such as Alzheimer's disease (AD). Currently, pathologists can only confirm diagnosis through post-mortem donated brains.

In the first-of-its-kind study, the researchers used flortaucipir PET to measure tau and florbetapir PET to assess amyloid-beta in 26 former NFL players, aged 40 to 69 years, who had at least one TBI or concussion, and cognitive, mood, and behavioral dyscontrol symptoms, and 31 men without these symptoms.

Study participants underwent neuropsychological tests and neuropsychiatric assessments to identify cognitive, behavioral, and mood problems. The researchers also collected data on the former NFL players' total years of play. They found that the rate of depression was high, about 80 percent, among former NFL players. And on a common test of memory, 35 percent of the former players had problems on the delayed recall on a verbal list learning task.

The investigators found significantly higher tau PET levels in the former NFL players as a group compared with the controls. They did not find individual differences in the two groups, however, because the signal was small and its location was too variable. On average, the team found the former NFL players had higher tau levels in the bilateral medial temporal (1.23 vs. 1.12; p< 0.001), left parietal (1.12 vs. 1.01; p< 0.001), and bilateral superior frontal (1.09 vs. 0.98; p= 0.002) regions of the brain, compared to asymptomatic controls.

The researchers also found that the amount of abnormal tau in the PET scans was associated with the number of years playing football. The more they played, the more tau deposits were detected.

The researchers found no association between tau deposition and scores on cognitive and neuropsychiatric tests. And they did not detect elevated amyloid neuritic plaque over all; only one of the controls and one former NFL player had a positive amyloid PET scan, which is similar to patients with AD. The finding suggests that the symptoms observed in the former athletes is not attributable to Alzheimer's disease, the researchers noted.

In an accompanying editorial, Allen H. Ropper, MD, deputy editor of NEJM wrote CTE diagnosis in living patients is still a work in progress, but the use of PET scans does help.

"The report in this issue certainly does strengthen the case that tau is the offender early in CTE, but other links remain to be clarified. The techniques for studying living biology, such as this use of tau ligand PET, are making a difference," he concluded.

Currently, Dr. Stern and his colleagues are working with other researchers on DIAGNOSE CTE, a longitudinal study that follows former NFL players, former college football players, and people with no history of contact sports play. The results are expected to be reported in early 2020.

Grants from Avid Radiopharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company, the National Institutes of Health, the State of Arizona, and the U.S. Department of Defense helped fund this study. Avid Radiopharmaceuticals provided all flortaucipir and florbetapir PET radiotracers.

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Stern RA, Adler CH, Chen K, et al. Tau positron-emission tomography in former national football league players. NEJM 2019; Epub 2019 Apr 10.

Friday, April 12, 2019

The timing of menopause, menarche, along with the duration of a woman's reproductive span, was associated with the risk for dementia, according to a new analysis in the March 28 online edition of Neurology.

Previous research has suggested that women have as much as a  50 percent greater lifetime risk of developing dementia than men. But the new analysis proposes that a woman's reproductive history is significantly associated with that risk.

In the prospective study, researchers found later age at menarche, younger age at menopause, shorter reproductive span, and hysterectomies appeared to elevate dementia risk.

Endocrine events that signal less estradiol exposure may play a role in modulating disease risk, according to the researchers, led by Paola Gilsanz, ScD, staff scientist at Kaiser Permanente Division of Research, Oakland, California.

"Our epidemiologic findings support prior basic science work suggesting neuroprotective effects of estrogen," the researchers wrote.

Previous studies have shown estradiol boosts neuronal resilience and repair. For example, estradiol has been shown to reduce inflammation, apoptosis, and tau hyperphosphorylation. However, research on estradiol exposure and women's reproductive history across life has yielded inconsistent findings.

To better understand the associations between estradiol lifetime exposure and dementia risk, the team analyzed data from 15,574 female members of Kaiser Permanente Northern California, an integrated health care system.

The members filled out questionnaires about menarche, menopause, and whether they had a hysterectomy, between 1964 and 1973. The average age was 40 to 55 years during this time.

In 1996, when electronic health records became available, the average age was 76.5 years old. A total of 6,137 who completed the questionnaire in midlife were still members of Kaiser and had not been diagnosed with dementia.

The researchers calculated the reproductive span (menopause age minus menarche age) for each participant and used medical records to determine which participants developed dementia, which included Alzheimer's disease, vascular dementia, and non-specified forms of dementia, later in life.

They adjusted for demographics and midlife health indicators (hypertension, BMI, smoking status) and late-life health indicators (stroke, diabetes, and heart failure).

Participants were followed until 2017, by which that time 42 percent had been diagnosed with dementia.

Of 6,137 women, the average ages at menarche and menopause were 13 and 45.1 years, respectively, resulting in a reproductive span of 32.2 years. A total of 34 percent of participants reported undergoing a hysterectomy. Among those who didn't report a hysterectomy, the average age at menarche was 13 years, the average age at menopause was 47.4 years, and the average reproductive span was 34.4 years.

The findings revealed that women who experienced menarche at age 16 years or older were at a 23 percent greater risk for dementia than those who experienced menarche at age 13 years.

Those with reproductive spans of less than 34.4 years were at a 20 percent elevated risk for dementia. Compared to the longest reproductive span (39 to 44 years), spans of 14 to 20 years were tied to a 55 percent higher risk for dementia; spans of 20 to 30 years had a 26 percent higher risk; and spans of 31 to 34 years were associated with a 26 percent higher risk.

Going through menopause before age 47.4 years was tied to a 19 percent greater risk of dementia than those who went through menopause at age 47 or later.

Hysterectomies were associated with an 8 percent elevated risk for dementia.

"Studies suggest that timing of surgical menopause influences dementia risk, with younger age associated with greater risk of dementia or cognitive impairment and AD pathology," the researchers wrote, about the potential influence of hysterectomies on dementia risk.

Overall, they concluded that later age at menarche or earlier age at menopause, along with the duration of a woman's reproductive span, was associated with an increased risk for dementia.

Although the study was diverse and large, the researchers did not have enough data to account for other factors that could affect estrogen levels, including pregnancies, hormone replacement therapy, or birth control.

Therefore, the researchers concluded, the findings warrant further research into how loss of estrogen at menopause can influence brain health.

The researchers report no relevant financial disclosures.

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Gilsanz P, Lee Catherine, Corrada MM, et al. Reproductive period and risk of dementia in a diverse cohort of health care members. Neurology 2019; Epub 2019 Mar 28.

Wednesday, April 10, 2019

Despite their known teratogenic risks, valproate, phenytoin, and topiramate are often prescribed to women of childbearing age with epilepsy, according to a new retrospective analysis published online on April 1 in JAMA Neurology.

The new paper identified these and other prescribing patterns in young women newly diagnosed with epilepsy.  The researchers noted that these prescribing patterns may be influenced by the presence of comorbidities in these women. Valproate and topiramate were often prescribed for women with certain comorbid conditions—valproate, for comorbid mood or anxiety and dissociative disorder, and topiramate for women with comorbid headache or migraine.  

"Physicians and women of childbearing age with epilepsy should be aware of and sensitive to teratogenicity risks of certain AEDs," the researchers, led by Hyunmi Kim, MD, PhD, MPH, of the department of neurology at Stanford University in California, wrote.

For their analysis, the team identified a total of 46,767 women with epilepsy, aged 15 to 44 years, from a U.S. nationwide commercial database and supplemental Medicare as well as Medicaid Insurance claims data from 2009 to 2013.They classified epilepsy diagnosis as either focal, generalized, or undefined.

Among their findings, the researchers reported that most newly diagnosed young women received monotherapy as first-line treatment for epilepsy, which is consistent with the 2018 guideline of the AAN and the American Epilepsy Society. And the most commonly prescribed AEDs were levetiracetam, lamotrigine, and topiramate for both incident and prevalent cases.

In other findings, topiramate—which is associated with a higher risk of cleft palate and small-for-gestational age newborns—and valproate, associated with behavioral and anatomic teratogenicity, were among the most frequently prescribed AEDs in women with either prevalent or incident (new) epilepsy treated with monotherapy or polytherapy.

Regardless of seizure types, levetiracetam, lamotrigine, and topiramate were among the top three most prescribed AEDs in women with epilepsy.

The researchers believe these findings align with recent evidence that suggests AED prescribing patterns have changed. For example, valproate use has decreased in women of childbearing age following recommendations against its use during pregnancy. Yet, they noted valproate was prescribed in a considerable proportion of women in this study.

"To improve current practice, knowledge of the teratogenicity of certain AEDs should be disseminated to health care professionals and patients," the researchers wrote.

They suggested a medical and patient information program could be implemented and monitored by assessing AED prescription patterns in a population-based cohort.

UCB Pharma sponsored the study. Dr. Kim reported receiving other from UCB Pharma during the study; other from UCB Pharma outside the submitted work. Co-authors reported disclosures related to UCB Pharma, Biogen, Eisai, SK Life Science, Brain Sentinel, UCB Pharma, and the University of Alabama at Birmingham.

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Kim H, Faught E, Thurman DJ, et al. Antiepileptic drug treatment patterns in women of childbearing age with epilepsy. JAMA Neurol 2019; Epub 2019 Apr 1.

Tuesday, April 9, 2019

Clinicians often changed their clinical management of Medicare beneficiaries with mild cognitive impairment (MCI) and dementia of uncertain etiology as a result of amyloid PET scans, according to the Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) trial, published online April 2 in the Journal of the American Medical Association (JAMA).

The study, the first phase  of a four-year effort to provide evidence for the clinical utility of amyloid PET scans, was in large part intended to address concerns of  the Centers for Medicare and Medicaid Service, which had previously concluded that there was insufficient evidence to justify routine coverage for amyloid PET scans, which can cost $4000 to $5000.CMS had agreed to consider coverage if studies could provide evidence that amyloid PET improves health outcomes, including changes in management as well as longer term dementia outcomes.

Among findings, the IDEAS investigators  reported that amyloid scans led to changes in diagnoses from Alzheimer's to non-Alzheimer's disease (AD) in 25.1 percent of cases and altered clinical management in about two-thirds of all patients, after 90 days.

"As reported in previous studies, use of amyloid PET was associated with frequent changes in diagnosis, improved diagnostic confidence, and reduced use of other diagnostic tests," the researchers, led by Gil Rabinovici, MD, of the University of California, San Francisco, wrote.

To assess whether amyloid PET has additional value in routine clinical practice, the team analyzed data from 16,008 Medicare beneficiaries ages 65 or older, enrolled in the IDEAS trial from February 2016 through September 2017. About 71.3 percent 16,008 registered participants (with a median age of 75 years old) completed the study. Participants either had a diagnosis of MCI or dementia established by a dementia specialist within the past 24 months.

A total of 946 dementia specialists from 595 unique practices across the U.S. participated in the study. The specialists documented participants' diagnosis and management plan before PET scans and then again 90 days after their PET.

Amyloid PET results were positive in 3817 patients with MCI (55.3 percent) and 3154 patients with dementia (70.1 percent).

The most common change clinical management after amyloid PET scans involved prescribing AD drugs, which occurred in 43.6 percent of patients with MCI and 44.9 percent of dementia patients. Clinicians also recommended counseling in 24.3 percent of MCI patients and 20.7 percent of dementia patients. PET results significantly influenced management in 85.2 percent of cases where a change was made, the investigators reported.

Amyloid PET results were negative (white matter retention only) in 36 percent of people with presumed AD etiology before PET; they were positive, however, in 52 percent of people with a pre-PET presumed non–AD etiology.

The study's non-randomized design and the fact that investigators did not compare amyloid PET with other Alzheimer's imaging or CSF biomarkers were among the study's limitations, the authors of the paper acknowledges. They also noted that the participants were made aware that PET results were expected to change diagnosis and treatment, and most participants were non-Hispanic whites, which does not reflect the racial and ethnic diversity of Medicare beneficiaries in the U.S.

The Alzheimer's Association, the American College of Radiology, Avid Radiopharmaceuticals (a wholly owned subsidiary of Eli Lilly and Company), General Electric Healthcare, and Life Molecular Imaging (formerly Piramal Imaging) funded the IDEAS trial.

The Centers for Medicare & Medicaid Services reimbursed PET scans.

Dr. Rabinovici reported relationships with Genentech, Eisai, Merck, Roche, Avid Radiopharmaceuticals, and Eli Lilly, and serves as associate editor for JAMA Neurology. Co-authors report other relevant disclosures in the full study.

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Rabinovici GS, Catsonis C, Apgar C, et al. Association of amyloid positron emission tomography with subsequent change in clinical management among medicare beneficiaries with mild cognitive impairment or dementia. JAMA 2019; Epub 2019 Apr 2.