Among community-dwelling adults over 60 — a population facing a 4.5% annual cumulative incidence of depression — physical activity (PA) engages at least three distinct neuroprotective mechanisms: enhanced cerebral blood flow and glucose utilization, upregulation of neurotrophic factors BDNF and IGF-1, and modulation of mood-regulating neurotransmitters including serotonin and dopamine. These changes accompany measurable structural adaptations in regions like the hippocampus, which is particularly vulnerable to age-related atrophy.
The mechanistic picture assembled here isn't new territory — BDNF's role in neuroplasticity has been studied for over two decades, and hippocampal volume responses to aerobic exercise were compellingly demonstrated in Erickson et al.'s landmark 2011 RCT. What's notable is the convergence of these pathways into a unified clinical argument: PA functions as a low-cost, multi-domain intervention with no meaningful side-effect profile compared to antidepressants or cognitive pharmaceuticals. For practicing clinicians, this matters enormously given the underdiagnosis of depression in older adults and the polypharmacy risks already present in this cohort.
However, as a narrative review rather than a systematic meta-analysis, this work carries inherent selection bias risks and cannot quantify effect sizes or optimal PA dosages — critical gaps for clinical prescribing. It is best categorized as confirmatory and synthesizing rather than paradigm-shifting, but its practical orientation toward healthcare professionals gives it genuine translational value.
