Exercise and intensive pharmacological interventions not linked to significant cognitive benefits in elderly: JAMA

A recent study published in the Journal of the American Medical Association found that exercise, intensive pharmacological management of cardiovascular risk factors, or their combination did not lead to statistically significant improvements in cognitive function over 24 months among older adults with a family history of dementia or subjective cognitive decline.

The study evaluated if targeting multiple modifiable cardiovascular risk factors (physical inactivity, high blood pressure, and high cholesterol) at once, offer stronger protection against cognitive decline. Across two years from 4 clinical sites this research enrolled 513 adults aged 60 to 85 who did not have dementia but were considered at elevated risk due to hypertension, a family history of dementia, or self-reported memory concerns. Participants were randomly assigned to one of four groups such as aerobic exercise, intensive pharmacological reduction of vascular risk factors (IRVR), a combination of both, or standard care.

The IRVR strategy aimed to lower systolic blood pressure below 130 mm Hg and reduce LDL cholesterol using medication. Meanwhile, the exercise group followed structured aerobic training programs. After 24 months, the results showed modest cognitive improvements across all groups, with no statistically significant differences between them.

Cognitive performance was measured using the Preclinical Alzheimer Cognitive Composite (PACC), to detect early changes associated with Alzheimer’s disease. Participants in the exercise group improved slightly more than those who did not exercise, but the difference was not statistically meaningful. Similarly, those receiving intensive cardiovascular treatment did not outperform those who did not receive it.

Secondary measures (cognitive tests assessing memory, attention, and processing speed), followed the same pattern of small gains across the board, but no clear advantage for any single intervention or combination. While the findings may seem surprising, they do not diminish the importance of managing cardiovascular health or staying physically active. Both exercise and vascular risk reduction are already well-established for improving heart health and overall well-being.

Cognitive decline is influenced by genetics, lifestyle, and underlying biological processes, by making it difficult for any single or combined intervention to produce dramatic short-term effects. Longer follow-up periods or earlier intervention in midlife may be necessary to detect more meaningful cognitive changes.

Reference:

Zhang, R., Vidoni, E., Vongpatanasin, W., Kerwin, D. R., Cullum, C. M., Rossetti, H., Stowe, A. M., Billinger, S. A., Gupta, A., Hall, T., Scheel, N., Zhu, D. C., Hynan, L. S., Burns, J. M., Keller, J. N., & Binder, E. F. (2026). Effects of exercise and intensive vascular risk reduction on cognitive function in older adults: A randomized clinical trial: A randomized clinical trial. JAMA Neurology. https://doi.org/10.1001/jamaneurol.2026.0359