In a family-based cohort of 1,050 adults (mean age 59.3 years), brain perivascular space (PVS) morphometry — quantified across centrum semiovale and basal ganglia using automated MRI segmentation — showed significant familial heritability for PVS volume (β=0.22) and median length (β=0.28), independent of vascular risk factors. Beyond aging's expected association with PVS burden, depressive symptoms correlated robustly with increased PVS density across both brain regions, elevated hair cortisol (a chronic stress biomarker) associated with higher PVS count, and weaker grip strength inversely predicted PVS volume — all independent of hypertension.
PVS are fluid-filled channels surrounding cerebral vessels that serve as conduits for the brain's glymphatic waste-clearance system; their enlargement is increasingly recognized as a marker of impaired glymphatic function potentially linked to neurodegeneration and dementia risk. What makes this analysis genuinely noteworthy is the simultaneous demonstration of both heritable microvascular architecture and modifiable neuropsychiatric determinants — particularly the depression-cortisol-PVS axis, which implicates chronic psychological stress as a cerebrovascular risk mechanism distinct from traditional cardiovascular factors. The grip-strength association aligns with emerging evidence linking systemic musculoskeletal fitness to cerebrovascular integrity. Limitations include cross-sectional design, which cannot establish causality, and borderline FDR-corrected significance for cortisol. Still, identifying that roughly a quarter of PVS variance reflects familial phenotypes positions PVS morphometry as a promising heritable endophenotype for future genetic and intervention studies targeting cerebrovascular aging.
