Exercise and neural circuit stability in early Alzheimer's disease: evidence across memory, executive, cholinergic, and circadian systems.

Early Alzheimer's disease (AD) is increasingly understood as a phase in which neural circuit dysfunction emerges alongside molecular pathology and local neuronal injury. Although physical exercise has been linked to a deceleration in cognitive decline and beneficial cognitive and neural outcomes, most mechanistic explanations have predominantly focused on molecular or cellular pathways, with less emphasis on circuit-level interpretations. This narrative review integrates evidence from four neural systems that exhibit early vulnerability in AD and are pertinent to exercise-responsive cognitive or behavioral domains: the entorhinal cortex-dentate gyrus (EC-DG) circuit, the ventral hippocampus-medial prefrontal cortex (vHPC-mPFC) pathway, the medial septum/vertical diagonal band-hippocampal (MS/VDB-hippocampal) cholinergic circuit, and the suprachiasmatic nucleus-paraventricular nucleus (SCN-PVN) circadian axis. Across these systems, the evidence remains inconsistent. Direct circuit-level findings, including electrophysiological and functional-connectivity measurements, indicate circuit disruption in specific domains, whereas many exercise-related effects are inferred from molecular, structural, neurochemical, behavioral, or clinical-proxy outcomes. We therefore propose a multicircuit framework in which exercise may ameliorate AD-related cognitive and behavioral dysfunction through convergent but circuit-specific routes: EC-DG excitability and plasticity, vHPC-mPFC communication substrates, MS/VDB-hippocampal cholinergic modulation, and SCN-PVN circadian-neuroendocrine timing. This framework clarifies the evidence boundaries of exercise-related circuit modulation in early AD and identifies direct circuit-level measurements as a priority for future translational studies.