The glymphatic system plays a critical role in clearing metabolic waste and neurotoxic proteins from the brain, and its dysfunction is implicated in neurodegenerative diseases such as Alzheimer’s disease (AD). Emerging evidence indicates that physical exercise enhances glymphatic function through multiple mechanisms, including increased cerebrospinal fluid (CSF) influx, improved perivascular clearance, astrocytic aquaporin-4 (AQP4) polarization, and modulation of vascular and sleep-dependent processes. Preclinical studies demonstrated that voluntary wheel running and aerobic exercise reduce amyloid-β (Aβ) accumulation, attenuate neuroinflammation, and improve cognitive performance in both aging and AD mouse models, with benefits being highly dependent on AQP4 expression and the timing of intervention. Translational evidence in humans showed that structured aerobic and multicomponent exercise increases glymphatic and meningeal lymphatic activity, enhances vascular dynamics, reduces systemic inflammation, and improves sleep quality, leading to measurable cognitive gains. Despite these promising findings, methodological challenges—such as limitations of non-invasive imaging, difficulty establishing causality, and reliance on short-term interventions—highlight the need for longitudinal, multimodal studies that integrate imaging, cardiovascular, sleep, and cognitive metrics. Collectively, these data suggest that exercise represents a potent non-pharmacological strategy to augment glymphatic clearance, preserve neural homeostasis, and reduce the risk of cognitive decline. This review will summarize evidence on exercise-induced glymphatic enhancement, highlight mechanisms, and identify research gaps for future studies on brain health.

The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) composite score is a promising measure connecting vascular health to cognitive decline; However, its association with brain imaging findings remains underexplored. This study aimed to evaluate the predictive value of the associations between CAIDE and structural brain measures in individuals with mild cognitive impairment (MCI). Participants (n = 226) aged 55–90 years with available CAIDE scores and white matter hyperintensity (WMH) measurements and a diagnosis of amnestic MCI were included. Regression models were used to evaluate the association between CAIDE score and neuropsychiatric and imaging findings. Higher CAIDE scores were significantly correlated with lower MMSE scores (r = -0.22, p = 0.001) and higher CDR-SB (r = 0.34, p < 0.001) and ADAS-Cog 11 scores (r = 0.38, p < 0.001). CAIDE scores were significantly positively related to total cerebrum (β = 0.319), gray matter (β = 0.337), and hippocampal volumes (β = 0.250, all p < 0.001). ROC analysis demonstrated that total gray matter (AUC = 0.70) and total brain (AUC = 0.69) were more accurate predictors of dementia risk compared to WMH volume (AUC = 0.52). Higher CAIDE dementia risk scores were linked to poorer cognitive performance but showed limited association with WMH burden in individuals with MCI. Gray matter and hippocampal volumes were stronger correlates of dementia risk than WMH volume and CAIDE-related risk may be better captured by cortical and hippocampal structural changes rather than white matter disease.