Gemfibrozil Impacts Metabolic and CVD End Points, Sildenafil Shows Promise in AD, Sensory Stimulation Shows Safety

This week Neurology News Network covered the impact of gemfibrozil on metabolic and cardiovascular disease end points in prodromal Alzheimer disease (AD), the use of sildenafil as a preventive for AD, and the self-administration safety of a gamma sensory stimulation device developed by Cognito Therapeutics.

Welcome to this special edition of Neurology News Network. I’m Marco Meglio. Please excuse our appearance this week as a majority of the US workforce, including the NeurologyLive team, moves to working remote as we come together to help reduce the spread of the novel coronavirus. This week, we covered the Alzheimer’s Association International Conference.

Data from a phase 2 safety study presented at the 2021 Alzheimer’s Association International Conference, July 26-29, showed that gemfibrozil (Lopid; Pfizer), a lipid-lowering drug, had a robust impact on metabolic and cardiovascular disease end points in patients with prodromal Alzheimer disease. Lead author Gregory A. Jicha, MD, PhD, professor of neurology, Alzheimer’s Disease Research Center, University of Kentucky College of Medicine, and colleagues concluded that the overlap in disease mechanisms and possible therapeutics for prevention of dementia caused by AD and or CVD is “remarkable.” Individuals were randomly assigned to treatment with gemfibrozil 600 mg orally twice daily or placebo for 48 weeks and were evaluated on safety, microRNA-107 levels, and amyloid-beta (Aß) levels. Treatment with gemfibrozil resulted in significant improvements in plasma glucose (P <.001), lipid levels (P <.001), and trends in CVD imaging biomarkers including reductions in WMHyperintensity volumes, accompanied by ASL perfusion increases in the dorsolateral prefrontal cortex (P = .13), hippocampus (P = .10), and posterior cingulate cortex.

Using a developed endophenotype molecular network-based methodology, investigators concluded that sildenafil (Revatio) is a promising drug candidate for prevention and treatment of patients with Alzheimer disease. Presenting author Feixiong Cheng, PhD, assistant professor, Department of Molecular Medicine, Cleveland Clinic, and colleagues validated their network-based predictions of promising AD drug candidates using state of-the-art pharmacoepidemiologic analysis of 7.23 million US commercially insured individuals. After 6 years of follow-up, investigators found that sildenafil use was significantly associated with a 69% reduced risk of AD compared with matched non-sildenafil use. Across all 5 drug cohorts, individuals with coronary artery disease (CAD), hypertension (HT), and type 2 diabetes (T2D) all had reduced likelihood of AD when using sildenafil.

A gamma sensory stimulation device, developed by Cognito Therapeutics, was found to be safe for self-administration at-home for patients with mild to moderate Alzheimer disease (AD), according to data presented by Martin Williams, BS. The investigators discussed the high daily adherence rate (90%) with the system, which uses noninvasive, visual and auditory gamma (40 Hz) sensory stimulation. Following clinic EEG to confirm gamma entrainment and device calibration, the study enrolled a total of 74 subjects, participating in the 6-month treatment study and randomized 2:1 into treatment and sham groups. The treatment group had a final mean adherence of 90.2%, compared to the sham group, which had a final mean adherence of 95.9%. Additional data from the phase 2 study, dubbed OVERTURE, showed that gamma frequency neuromodulation over the 6-month period reduced nighttime active durations and maintained daytime activities in this patient population.

For more direct access to expert insight and coverage of AAIC 2021, head to NeurologyLive.com. This has been Neurology News Network. Thanks for watching