Dr. Judy Heidebrink shares an update on Alzheimer's disease clinical trials

Dr. Judy Heidebrink shares an update from the Clinical Trials on Alzheimer's Disease Conference in the January e-newsletter. 

What have we learned from recent clinical trials about the prevention and treatment of Alzheimer’s disease and other dementias? 

To begin, the U.S. POINTER study demonstrated the cognitive benefits of a multi-component lifestyle intervention. In this study, individuals age 60-79 who had a sedentary lifestyle and a suboptimal diet, along with other risk factors for dementia, were assigned to either a structured or a self-guided lifestyle intervention for two years. Both interventions promoted a healthy diet, cardiovascular health monitoring, and physical, cognitive, and social activity. The main difference was the level of support and monitoring. For example, the structured group had specific activity plans and 38 meetings with study team members, whereas the self-guided group received educational materials and met six times. Cognitive scores improved in both groups, with the structured group showing greater improvement—equivalent to being one to two years younger. The U.S. POINTER study provides even more reason to make a brain-healthy lifestyle part of your New Year’s resolutions.

Can we get similar results by taking a medication that targets cardiometabolic health? 

One answer comes from the Evoke/Evoke+ trials of semaglutide. Semaglutide is a pill medication that mimics glucagon-like peptide-1 (GLP-1), a natural hormone that regulates appetite and blood sugar. Semaglutide is used to treat diabetes and obesity, and was recently studied as a potential treatment for Alzheimer’s disease. In the Evoke/Evoke+ trials, individuals with early symptomatic Alzheimer’s disease received either semaglutide or a placebo for two years. Although the semaglutide recipients had changes in metabolic markers and were more likely to lose weight, there was no difference in cognition or daily function compared to the placebo group.

What about amyloid-lowering therapies? 

Two FDA-approved antibodies that remove brain amyloid, lecanemab and donanemab, continue to be used clinically in persons with early symptomatic Alzheimer’s disease. Open label studies of both have shown long-term benefits in slowing cognitive decline. Clinical trials are ongoing with other anti-amyloid antibodies. Remternetug appears to clear brain amyloid quickly and is being studied as either an intravenous infusion or a subcutaneous (under the skin) injection that could be given at home. Trontinemab has a novel mechanism that allows it to enter the brain more easily and evenly. Based on initial studies showing rapid amyloid clearing and a very low rate of side effects, trontinemab is entering pivotal phase three trials. All of these antibodies are also being studied in prevention trials to see if they can prevent the emergence of Alzheimer’s disease symptoms.

Anti-amyloid therapy will be combined with anti-tau therapies in the upcoming Alzheimer’s Tau Platform (ATP) Clinical Trial. This trial will enroll individuals with very early symptoms, as well as individuals at risk but without current cognitive impairment. The ATP trial will be launching soon. Why not make “join a study” one of your resolutions for the New Year?

Dr. Heidebrink presents "What's New in Alzheimer's Disease Clinical Trials" as part of the January speaker series.