Research Highlights From Padmaja Genesh (May 2020)
How Aerobic Exercise Helps us Keep Our Wits About Us As We Age
University of Calgary study shows it is never too late to see the brain benefits from regular exercise.
Source: Neurology Journal Published May 13 online
Potential Agitation Treatment, AXS-05, Shows Efficacy and Safety in Phase 2/3 Trial
FDA Filing of Alzheimer’s Therapy Aducanumab Delayed to Late 2020, Biogen Says
Aducanumab was investigated in ENGAGE () and EMERGE (), two Phase 3 trials that evaluated two doses of Aducanumab in people with mild cognitive impairment due to Alzheimer’s and mild Alzheimer’s dementia.
In March 2019, after 1,748 patients in both trials completed the 18 months of treatment, a monitoring committee said Aducanumab was not likely to produce meaningful benefits for patients. This led to the and two other trials testing Aducanumab in Alzheimer’s.
A — including a larger population of 3,285 patients, 2,066 of whom completed the full 18 months of treatment — ultimately showed that EMERGE met its primary goal. In that analysis, high-dose Aducanumab significantly slowed the progression of cognitive and functional impairment, compared with a placebo. were also significantly better for patients receiving Aducanumab over the 18 months, compared to placebo.
These findings led it would seek approval of Aducanumab for Alzheimer’s disease. If approved, this would be the first Alzheimer’s therapy that treats the disease directly rather than alleviating symptoms, and would be the first new Alzheimer’s treatment for nearly two decades.
To continue studying the long-term safety and tolerability of Aducanumab, Biogen launched the open-label Phase 3 EMBARK trial to start re-dosing Alzheimer’s patients who participated in the four studies halted in 2019. The first patient has been dosed in the Phase 3 EMBARK clinical trial ().
Flortaucipir Autopsy Study Published
Results from a large autopsy validation study suggest that flortaucipir PET can help clinicians diagnose late-stage Alzheimer’s disease. In the April 27 JAMA Neurology, researchers led by Adam Fleisher at Avid Radiopharmaceuticals/Eli Lilly, Indianapolis, report that visual reads of brain scans predict tau pathology with a sensitivity above 92 percent.
The study (A 16) involved 156 volunteers, who were terminally ill and who had agreed to a flortaucipir scan.
Tau positivity also predicted AD pathology- both plaques and tangles as outlined by the NIA-AA neuropathologic criteria for AD. In a JAMA Neurology editorial, William Jagust, University of California, Berkeley, wrote that the study is a step toward validating methods crucial to improving the understanding of brain aging and AD
Other experts too agreed that the study is very well performed one and supports the use of flortaucipir in the clinical diagnostic work-up of patients with cognitive impairment where AD is considered to be one of several possible etiologies.
How, or if, this scan may be used in the clinic remains unclear. The first PET ligand for amyloid, Avid’s florbetapir, was approved by the FDA eight years ago, and two more quickly followed suit (; ; ). However, they have not yet been cleared for reimbursement by the Centers for Medicare and Medicaid Services, despite data showing that amyloid PET scans help doctors tailor patient care ().
Large Study Finds No Evidence That Low-dose Aspirin Reduces Alzheimer’s Risk
Aspirin is a widely-used anti-inflammatory medication. Increased , particularly in the brain, has been with the development of Alzheimer’s disease. Because of this, low-dose daily aspirin is thought to , but this idea hasn’t been rigorously tested.
The Aspirin in Reducing Events in the Elderly (ASPREE) clinical trial () enrolled 19,114 people, 70 or older, in Australia and the United States. For African-American and Hispanic participants in the U.S., the age limit was lowered to 65 years, because of their higher risk of disease. At enrollment, all participants had no signs of dementia or heart disease.
Participants were randomized to take 100 mg daily of aspirin (9,525 people), or a placebo (9,589). Participants were followed via regular phone calls and annual in-person meetings. A battery of cognitive assessments was administered after the first year, then every other year.
Participants in both groups were followed for a median of 4.7 years (range 3.6–5.7 years). In this time, 283 people in the aspirin group were diagnosed with dementia, as were 292 people in the placebo group.
The disease rate was not significantly different at just under three events per 1,000 person-years in each group. The rate of cognitive decline (a significant decrease in cognition scores over time) — about 25 events per 1,000 person-years — was also not significantly different between the groups. No differences were found between the groups in subgroup analyses, including age, sex, ethnicity, health factors, and prior use of aspirin or .
It is worth noting that the rates of dementia and MCI in the ASPREE study are somewhat lower than what has been reported in , which may have decreased the statistical power of this study to detect significant differences between the groups. The researchers who authored the study speculated that “this lower incidence is likely explained by the inclusion of participants who were relatively healthy at baseline.”
Study of US Veterans Points to a Connection Between Late-Onset Seizures and Dementia
An analysis of data from the US Veterans Health Administration National Patient Care Database suggests that late-onset seizures of unknown etiology are associated with an increased risk of dementia in older veterans.
Late-onset seizures may be an early sign of dementia, according to a retrospective study involving nearly 300,000 veterans.
Veterans who were diagnosed with late-onset seizures of unknown cause were nearly twice as likely to be diagnosed with dementia over the next several years.
“While seizures are commonly thought to occur in late stages of dementia, these findings suggest unexplained seizures in older adults may be a first sign of neurodegenerative disease,” said the authors of the study, reported online in JAMA Neurology.
Ophir Keret, MD, the study's first author and an Atlantic Fellow at the Global Brain Health Institute at the University of California, San Francisco (UCSF), said that while more research is needed on the relationship between late-onset seizures and dementia, the new findings should “encourage clinicians to follow these patients more closely for cognitive decline and possible intervention.”
Dr. Keret, who conducted the study with senior investigator, Kristine Yaffe, MD, professor of psychiatry, neurology and epidemiology at UCSF, said a prospective study of non-veterans with late-onset seizures of unknown origin would help to better understand the risk and course of cognitive decline.
Because the UCSF study focused solely on veterans, almost all male, the findings may not apply to the general population. People who get their care at the VA also tend to have poorer health overall, which may have influenced the results. Another limitation of the study is that it relied on diagnostic codes, which aren't always accurate, as opposed to reviewing medical records. Data on seizure severity and subtype as well as dementia subtype were limited.
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