REVIEW OF: Tari AR et al, Lancet 2025;405(10484):1093–1118

STUDY TYPE: Narrative review
“Stay active” has been standard advice for decades, but patients may need to hear more specifics for the advice to be useful. This narrative review synthesized evidence from animal models, observational studies, and RCTs to clarify how endurance exercise protects the aging brain at molecular, cellular, and clinical levels.

Aerobic exercise increases cerebral blood flow to the hippocampus, grows hippocampal volume, and reduces age-related atrophy through neurogenesis and synaptic remodeling that few other interventions can match. It also triggers release of exerkines, signaling molecules that cross the blood-brain barrier and boost BDNF, IGF-1, and other factors supporting neuronal survival and plasticity.

The key variable isn’t time on one’s feet but cardiorespiratory fitness, which predicts dementia risk and longevity more strongly than activity level alone, and only improves when cardiovascular demand is genuinely high. Just 30 minutes per week of high-intensity exercise (roughly 85% max heart rate; vigorous enough to speak briefly but not sing) reduced all-cause mortality by ~40%, dementia risk by 30%, and dementia-related mortality by ~40%.

CARLAT TAKE
Prescribe intensity instead of steps. For deconditioned patients, brisk walking with hills or stair climbing is a good start; for those already active, push toward jogging, cycling, or intervals. The goal is sustained elevated heart rate, a low-cost intervention with an effect size rivaling most pharmacologic options for dementia prevention. Make it specific: “I want you sweating and breathing hard for 10 minutes, three times a week.”