Exercise initiated in early life promotes cognitive resilience and prevents neurodegeneration

Alzheimer's disease (AD) accounts for approximately 60%–70% of the over 55 million dementia cases worldwide, representing a global public health crisis with 139 million cases anticipated by 2050. Physical inactivity is an important risk factor for dementia. This narrative review provides a synopsis of evidence supporting the hypothesis that physical activity initiated in early life can establish resilience against cognitive decline and AD. For example, early-life exercise robustly upregulates brain-derived neurotrophic factor (BDNF) signaling, resulting in approximately a twofold increase in hippocampal BDNF, thereby supporting synaptic plasticity and neuronal survival. Further, exercise induces lasting epigenetic reprogramming, including demethylation of BDNF gene promoters, which lead to transcriptional effects favorable to brain health across the lifespan. Lastly, exercise reduces neuroinflammation and enhances mitochondrial and neurovascular function in ways that persist well beyond exercise itself. Taken together, this evidence suggests that early-life physical activity may shift the trajectory of cognitive aging, build lasting cognitive resilience, and delay the onset of AD. The implications for prevention policy and the design of longitudinal intervention studies are considerable.