Gait Impairment and Alzheimer's Disease Pathology: A Narrative Review on Mechanistic Links

In older adults, gait has emerged as an important indicator of overall health and a strong predictor of adverse outcomes, including dementia. This association has been corroborated by findings from Alzheimer's disease (AD) research. In AD, amyloid-β brain accumulation is succeeded by tau pathology and neurodegeneration, commencing within the medial temporal lobe. Older adults exhibiting slower gait speed or reduced gait adaptability display greater amyloid and tau brain deposition, as well as more pronounced hippocampal atrophy, suggesting that gait impairment may serve as an early clinical marker of AD-related neurodegeneration. Despite accumulating evidence linking gait impairment to AD-related pathology, the underlying mechanisms remain inadequately understood. Traditional explanations have focused on shared neural substrates, including frontal-subcortical and motor control networks, which decline with aging and result in parallel deterioration of gait and executive function. Although this framework aligns with cognitive reserve theory, it fails to fully explain the potential pathways linking gait disturbances to AD-related and mixed brain pathology. In this review, we explore interacting mechanisms suggesting that gait impairment and AD-related changes may arise from common vulnerabilities and mutually reinforcing processes. By synthesizing the current evidence, we aim to advance the understanding of gait decline as a prodromal symptom of dementia, advocate for early screening of gait performance, and highlight the importance of maintaining gait function across the lifespan as part of healthy aging strategies that may help delay the onset of dementia. The conclusion underscores a life-course perspective on health, rather than one that focuses solely on functional decline in old age.