A new clinical trial suggests that improving cardiovascular health alone may not be enough to protect older adults from cognitive decline associated with Alzheimer’s disease. Researchers found that while exercise and intensive management of cardiovascular risk factors significantly improved physical health measures, these interventions did not lead to measurable improvements in cognitive function over two years among older adults considered at risk for Alzheimer’s disease.
The findings were published in the JAMA Neurology study, “Effects of Exercise and Intensive Vascular Risk Reduction on Cognitive Function in Older Adults – A Randomised Clinical Trial.” The research team, which included Jeffrey Keller of the Pennington Biomedical Research Center, examined whether exercise, medication-based vascular risk reduction, or a combination of both could help preserve cognitive function in older adults vulnerable to Alzheimer’s disease. Their findings revealed a striking disconnect between improvements in cardiovascular health and changes in brain function.
“We improved the body, but not the brain,” said Dr. Keller, who leads the Institute for Dementia Research and Prevention at Pennington Biomedical. He noted that although exercise and cardiovascular risk management remain essential for overall health, the results suggest that these strategies alone may not be sufficient to improve cognition in older adults already at increased risk for Alzheimer’s disease. The findings underscore the complexity of dementia prevention and point to the possible need for broader, multi-dimensional approaches that target several risk factors simultaneously.
The multicentre Risk Reduction for Alzheimer’s Disease (rrAD) study involved 480 participants between the ages of 60 and 85. All participants had hypertension, a family history of dementia, and subjective cognitive decline, placing them at elevated risk for Alzheimer’s disease. Over 24 months, researchers assigned participants to one of four groups: exercise only, medication intervention only, both exercise and medication, or usual care. The exercise intervention consisted of 160 minutes per week of moderate-to-vigorous physical activity, while the medication strategy used intensive vascular risk reduction methods, including statins and blood pressure medications such as losartan and amlodipine.
Researchers assessed cognitive performance using the Preclinical Alzheimer Cognitive Composite (PACC), a standardised tool designed to measure subtle cognitive changes associated with early Alzheimer’s disease. At the conclusion of the study, there were no statistically significant differences in cognitive outcomes between the intervention groups and the control group. The exercise intervention produced only a 0.1 standard deviation difference in PACC scores compared with participants who did not exercise. In contrast, the medication intervention showed no measurable cognitive advantage over those who did not receive the medications.
Although cognitive outcomes remained unchanged, the interventions successfully improved cardiovascular health indicators. Participants receiving the medication intervention experienced an average reduction of 13 points in blood pressure, approximately five points greater than those not receiving the treatment. LDL cholesterol levels also declined substantially, dropping by 24 points in the medication group compared with seven points among participants without the intervention. Researchers emphasised that exercise and cardiovascular risk management continue to provide major benefits for healthy ageing, even if cognitive improvements were not observed during the study period. They suggested that future studies with longer follow-up periods or more comprehensive, multi-domain prevention strategies may provide a clearer understanding of how to delay or prevent cognitive decline associated with Alzheimer’s disease.
More information: Rong Zhang et al, Effects of Exercise and Intensive Vascular Risk Reduction on Cognitive Function in Older Adults – A Randomized Clinical Trial, JAMA Neurology. DOI: 10.1001/jamaneurol.2026.0359
Journal information: JAMA Neurology Provided by Pennington Biomedical Research Center
