Trial Pairing Exercise With Intensive Vascular Treatment Finds No Added Cognitive Benefit

A randomized trial of 513 older adults tested aerobic exercise, intensive blood pressure and cholesterol lowering, and the two combined against usual care. After two years, none of the four groups pulled ahead on a standard cognitive test.

A four-site randomized trial that paired structured aerobic exercise with intensive drug treatment for blood pressure and cholesterol found no statistically significant improvement in cognitive test scores after two years compared with usual care, researchers reported in JAMA Neurology, published online March 23, 2026. The trial, known as rrAD (Risk Reduction for Alzheimer's Disease), is among the first to test a combined exercise-plus-drug approach against each component alone and against standard care in the same randomized design.

The study enrolled 513 adults aged 60 to 85 who did not have dementia but had hypertension, a family history of dementia, or self-reported memory concerns. Participants were randomly assigned in equal groups to one of four arms: supervised aerobic exercise, intensive pharmacological lowering of systolic blood pressure to below 130 mmHg plus LDL cholesterol reduction with atorvastatin, the combination of both, or usual care. The primary measure was change on the Preclinical Alzheimer Cognitive Composite (PACC), a battery designed to detect early, subtle cognitive change.

At 24 months, PACC scores rose by 0.3 units in the exercise group versus 0.2 units in those who did not exercise, a difference the authors report was not statistically significant. Scores rose by 0.2 units in the intensive drug-treatment group versus 0.3 units in those who received usual vascular care, also not a significant difference. Secondary cognitive tests measuring memory, attention and processing speed followed the same pattern: small gains across all four arms, with no arm, including the combined exercise-plus-drug group, separating from the others.

The trial's own investigators framed the gap as a puzzle rather than a failure of the underlying vascular treatments, which did lower blood pressure and cholesterol as intended. "We improved the body, but not the brain," said Jeffrey Keller of Pennington Biomedical Research Center, one of the study's investigators, according to a statement from the center. The result stands in contrast to observational research linking cardiovascular risk factors to later dementia risk, and the authors note it does not overturn the case for treating hypertension or high cholesterol for heart and stroke reasons; it shows only that, in this trial, those treatments did not move a cognitive composite score over two years.

The investigators say the null result may reflect the trial's two-year window and a study population that was not yet cognitively impaired at enrollment, leaving open whether longer follow-up or intervention in people with more advanced vascular disease would show a different pattern.