Shared Mechanisms in Dementia and Depression: The Modulatory Role of Physical Exercise

Abstract

Dementia and depression are two prevalent disorders that warrant significant attention due to their high prevalence and substantial contribution to the global burden of disease. Depression has a high incidence in the elderly and is considered a risk factor for the development of dementia, being a promising target for dementia prevention strategies. Additionally, dementia and depression share common mechanisms through which they manifest pathologically. This review addresses the potential shared mechanisms between dementia and depression, including hypothalamic–pituitary–adrenal (HPA) axis dysfunction, brain atrophy (mainly hippocampus and prefrontal cortex), cognitive decline, and neuroinflammation. It also explores the therapeutic potential of physical exercise in modulating these shared pathways, highlighting its role as a non-pharmacological intervention for the treatment and prevention of both disorders. The review also explores the muscle–brain crosstalk and the intracellular pathways through which physical exercise exerts its effects.