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

Wednesday, February 22, 2017

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BY SARAH OWENS

A new analysis of 20-year follow-up data on a large, homogenous population found no strong evidence of a protective association between postmenopausal hormone therapy use and incident Alzheimer's disease or dementia, according to a new study published online on February 15 in Neurology.

While estrogen has been shown to have a neuroprotective effect in experimental trials, those results have not yet translated to clinical trials of postmenopausal hormone therapy, and observational and register-based studies have yielded conflicting results.

"While women still need to talk to their doctors about the risks and benefits of taking hormone therapy during menopause, this study did not provide strong evidence that taking hormone therapy can protect women from Alzheimer's disease," said study author Bushra Imtiaz, MD, MPH, researcher at the University of Eastern Finland in Kuopio, in a press release accompanying the study.

For the study, researchers at the University of Eastern Finland obtained follow-up data from the Kuopio Osteoporosis Risk Factor and Prevention Study cohort. Researchers sent a baseline questionnaire of demographic and health information to all women between the ages of 47 and 56 living in Kuopio Province in Eastern Finland in 1989. Every five years thereafter, for a total follow-up of 20 years, they sent a follow-up survey on which respondents reported the type, dosage, and number of months per year of hormone therapy use. Additionally, researchers used a Finnish national registry to identify hormone therapy prescriptions after 1995 and to identify all clinically verified diagnoses of Alzheimer's disease.

They found that 227 cases of incident dementia occurred in 8,195 women who completed all questionnaires. In an initial analysis, the researchers found that use of hormone therapy was not associated with Alzheimer's disease. After adjusting for lifestyle and socioeconomic confounders, they found that neither register-based nor self-reported hormone therapy use was linked with a risk of Alzheimer's disease, and there was no association between duration of its use and AD.

The researchers noted a number of limitations to their study. Among them, self-reported information may have been affected by recall bias; long-term users may have exhibited a healthy user bias; and researchers were not able to control for a genetic predisposition to Alzheimer's, such as that conferred by apolipoprotein E status and familial Alzheimer's disease.

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Thursday, February 16, 2017

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BY SARAH OWENS

Non-pharmacologic approaches should be used as first-line treatment for patients with low back pain, according to a new clinical practice guideline by the American College of Physicians (ACP) published in the February 13 online edition of  Annals of Internal Medicine.

The current guideline – which updates the ACP's 2007 guideline for low back pain– offers treatment guidance based on the efficacy, effectiveness, and safety of both pharmacologic and nonpharmacologic approaches for acute (lasting less than four weeks), subacute (lasting between four and 12 weeks), and chronic low back pain (lasting more than 12 weeks).

"Physicians should consider opioids as a last option for treatment and only in patients who have failed other therapies, as they are associated with substantial harms, including the risk of addiction or accidental overdose," said Nitin S. Damle, MD, MS, MACP, president of the ACP, in a press release accompanying the guideline.

To develop the evidence-based guideline, researchers for the Agency for Healthcare Research and Quality's Pacific-Northwest Evidence-Based Practice Center conducted a systematic review of randomized, controlled trials and reviews of studies published between January 2008 and November 2016.

Non-pharmacologic treatments reviewed included psychological therapies, acupuncture, massage, exercise, and multidisciplinary rehabilitation. Pharmacologic treatments reviewed included nonsteroidal anti-inflammatory drugs (NSAIDS), opioids, and skeletal muscle relaxants. The researchers evaluated a wide range of outcome measures, including reduction or elimination of pain, improvement in health-related quality of life, reduction in work disability, return to work, and adverse effects.

Based on the current literature, the researchers concluded that non-pharmacologic treatment should be first-line therapy for all patients with low back pain. For patients with acute or subacute back pain, treatment with superficial heat is supported by moderate-quality evidence, while massage, acupuncture, and spinal manipulation are supported by low-quality evidence. For those with chronic back pain, moderate-quality evidence supported a wide variety of treatments, including exercise, acupuncture, yoga, tai chi, mindfulness-based stress reduction, and cognitive behavioral therapy.

If patients with chronic low back pain have not responded to non-pharmacologic therapy, the researchers noted, then clinicians may consider pharmacologic treatment, but should first try NSAIDS or muscle relaxants. Only after these, too, have failed should doctors prescribe opioids, and only then if the benefits outweigh the potential risks, and they must first have a thorough conversation with the patient about those benefits and risks.

The researchers noted several limitations to their review. Among them, insufficient evidence exists to assess certain treatments, such as those for radicular low back pain; and most of the randomized, controlled trials reviewed enrolled a mixture of patients with acute, subacute, and chronic back pain, which makes it "difficult to extrapolate the benefits of treatment compared with its duration."

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Wednesday, February 15, 2017

BY SARAH OWENS

Metabolic plasma profiling of mildly affected patients with Parkinson's disease identified 15 biomarkers that strongly predicted disease progression up to two years later, according to a new study published online on February 8 in Neurology.

Previous efforts at identifying biomarkers have focused on PD pathology in the brain, but recent research indicates this scope may be too narrow, since proteins associated with PD, such as alpha-synuclein, have been shown to spread throughout the body. Researchers hypothesized that a metabolomic analysis, which measures "hundreds of low-molecular-weight compounds in biospecimens" may be able to identify biomarkers in plasma that can predict the progression of PD.

The findings yielded several biomarkers strongly capable of predicting PD progression, the study authors, led by Peter A. LeWitt, MD, director of the Parkinson's Disease and Movement Disorders Program at Henry Ford Hospital in West Bloomfield, MI,  and professor of neurology at Wayne State University School of Medicine, wrote. "Having biomarkers could provide insights into sub-types of PD and might be useful in assessing the effectiveness of neuroprotective treatments," Dr. LeWitt said in an interview about the study appearing in the March 2 issue of  Neurology Today.

For the study, researchers twice collected concentrated samples of plasma and cerebrospinal fluid (CSF) from 49 mildly affected patients with PD: once at baseline and once at a final assessment up to two years later. They used ultra-high-performance liquid chromatography to identify small-molecule plasma constituents in the samples. At baseline and final assessment, the researchers assessed the patients' disease progression using questions from the Unified Parkinson's Disease Rating Scale (UPDRS) parts 2 and 3, which comprise an assessment of daily living activities and motor skills.

The researchers identified 15 baseline plasma constituents with a high positive correlation to changes in parkinsonian severity (0.87 correlation coefficient, p=2.2e-16). However, the CSF samples showed little change between the baseline and final assessments and had minimal correlation with change in UPDRS scores.

The findings, the study authors concluded, "discern a biochemical profile linked to PD progression," although they do not clarify whether the observed markers are manifestations of the disease process. They also imply "several new directions for investigation of PD pathogenesis." For example, one of the biomarkers identified, serine, has neurochemical properties that may pertain to PD and is involved in the synthesis of an antioxidant that is diminished in PD.​

Look for expanded coverage of the study in the March 3 issue of Neurology Today.

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Friday, February 10, 2017

BY SARAH OWENS

Older US adults who have been diagnosed with new-onset epilepsy were often prescribed older antiepileptic drugs and experienced delays in treatment beyond 30 days, according to a new analysis of Medicare claims data published online on February 7 in Epilepsia.

However, nearly 95 percent of these patients received monotherapy in concordance with recent guidelines, and treatment patterns were similar across racial and ethnic groups, researchers found.

Older adults with new-onset epilepsy can be hard to treat due to a high rate of comorbidities, and research has shown they tend to receive delayed treatment with older antiepileptic drugs (AEDs) like phenytoin instead of newer AEDs like lamotrigline and gabapentin. The Quality Indicators of Epilepsy Treatment (QUIET 6) measures, which were developed in 2007 by a 10-member panel of epilepsy experts who appraised national clinical guidelines and systematic literature reviews to establish 24 evidence- and patient-based indicators of quality adult epilepsy care, recommends that older adults with new-onset epilepsy receive monotherapy as their initial treatment. The current analysis suggests that while treatment of such patients does concord with QUIET 6, they continue to receive delayed treatment with older AEDs.

As a result of the findings, "interventions should be developed and tested to develop paradigms that lead to better care," the study authors, led by Roy C. Martin, PhD, associate professor of neurology at the University of Alabama at Birmingham, wrote.

For their study, researchers at the University of Alabama at Birmingham and Emory University in Atlanta conducted a retrospective analysis of Medicare administrative claims made between 2008 and 2010 for a 5 percent random, racially diverse sample of Medicare Part D beneficiaries. They identified 3,706 cases of new-onset epilepsy. Over the year following diagnosis, they assessed patterns of AED use and compliance with QUIET 6 guidelines.

They found that 79.6 percent of all new-onset epilepsy cases received only one AED. Among these patients, the most commonly prescribed AED was levetiracetam, a newer AED, which was prescribed to 45.5 percent of patients. The second most commonly prescribed AED was phenytoin, an older AED (30.6 percent). Only 50 percent of new-onset epilepsy cases received prompt treatment within 30 days. However, compliance with the QUIET 6 guidelines was high, at 94.7 percent. Race and ethnicity were not significantly associated with patterns of AED treatment.

The results, the study authors wrote, are both "encouraging and concerning." The use of a newer AED as the most popular first-line monotherapy may indicate a "possible prescribing shift" away from outdated AEDs. However, they added, newer AEDs are still not prescribed as often as they should be, and delays in treatment are troubling and should be targeted in new intervention efforts. These delays may be "due to difficulty in recognizing/diagnosing epilepsy at older ages given the clinical presentation," they noted.

The researchers acknowledged several limitations to their study. Among them, they said the administrative claims database may not adequately identify cases of epilepsy, especially since coding changes took place during the course of the study. In addition, the sample was confined to beneficiaries of Medicare Part D fee-for-service claims, which may limit the generalizability of the findings.

Look for expanded coverage of the findings in an upcoming issue of Neurology Today.

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Thursday, February 2, 2017

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BY SARAH OWENS

Women who live in areas of the United States where levels of fine particulate matter in the air exceed Environmental Protection Agency (EPA) standards had nearly double the risk of developing global cognitive decline and all-cause dementia, and carrier status for apolipoprotein e4 appeared to exacerbate this risk, according to a new study published on January 31 in Translational Psychiatry.

The association between environmental factors and dementia is poorly understood, but epidemiologic evidence and preliminary findings from animal models suggest that fine particulate matter (PM), or air pollutants with aerodynamic diameters < 2.5 microns (PM2.5), have neurotoxic effects. The current study suggests that long-term exposure to PM can accelerate global decline and dementia.

"The association between PM exposure and increased dementia risk suggests that the global burden of disease attributable to PM pollution has been underestimated, particularly in regions with large populations exposed to high ambient PM," the study authors, led by Mafalda Cacciottolo, PhD, postdoctoral research associate at the Leonard Davis School of Gerontology at the University of Southern California, wrote.

The study combined a neuroepidemiologic analysis of a prospective cohort of US women to investigate the strength of the association and experiments on transgenic mice to investigate possible underlying mechanisms. Researchers analyzed data from the Women's Health Initiative Memory Study (WHIMS), a prospective nationwide cohort of women in the United States, ages 65-74, who were free of dementia at the beginning of the study. WHIMS participants had undergone annual screenings for global cognitive function plus neuropsychological and functional assessments, which blinded raters used to diagnose dementia and global cognitive decline.

The researchers used a statistically validated model incorporating monitoring data from the US EPA Air Quality System to estimate ambient levels of PM2.5 at all residential locations in the WHIMS study over a three-year period beginning in 1999 or 2000, accounting for relocations. They classified three-year exposures as "high" if they exceeded the EPA's National Ambient Air Quality Standards for PM2.5. Then they used time-to-event analyses to evaluate the link between long-term PM exposure and adverse cognitive outcomes.

They found that that women who lived in areas with high PM exposures over a three-year period had a significantly increased risk for global cognitive decline and all-cause dementia. For women living in high PM areas, the hazard ratio (HR) for global cognitive decline increased by 81 percent, while the HR for all-cause dementia increased by 92 percent. Those with the APOE e4 allele had the highest increased risks (HR of 3.95 for global cognitive decline and 2.95 for dementia).

Supplemental experiments on transgenic mice offer clues about the underlying mechanisms of the association between PM and cognitive decline. Mice who were exposed to PM over 15 weeks had increased cerebral beta-amyloid production, increased amyloid-beta oligomers, and selective atrophy of hippocampal neurites. The researchers hypothesized that these effects, when induced by PM, lead to cognitive decline.

The researchers noted, among other limitations, that the study of women may not be generalizable to men. In addition, they said, their analysis did not include information on the type of particles, emission sources, or interaction with other pollutants; and they only used data on PM exposure after 1999, a time period when air pollution has begun to decline, so long-term PM exposure may have been underestimated.

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