Intervention points for the role of physical activity in prevention and treatment of Alzheimer's disease

Alzheimer's disease (AD) is a growing global health challenge with limited pharmacological treatments. Epidemiological studies link regular physical activity with a lower risk of AD and cognitive decline in general, whereas randomized controlled trials show that aerobic exercise slows disease progression and improves cognitive function. However the underlying mechanisms remain incompletely understood. In this review we discuss five likely intervention points through which physical activity may influence AD progression and pathology: (1) reducing neuroinflammation and amyloid beta (Aβ) aggregation, (2) enhancing clearance of Aβ aggregates, (3) increasing neuronal resilience, (4) promoting hippocampal neurogenesis and (5) strengthening cognitive reserve. Understanding which of these mechanistic links are most likely to drive the AD-protective effects of exercise could help refine lifestyle-based interventions to complement pharmacological treatments and inform future prevention strategies.