Stress, Depressive Symptoms, and Physical Strength Impact Brain Perivascular Spaces: A Cohort Study with Insights from First-Degree Relatives

Stress, depressive symptoms, cardiovascular health, and physical strength are well-recognised factors that contribute to microcirculatory changes in the brain. However, there is limited understanding of their impact on perivascular waste clearance. In this study, we used the Stratifying Depression and Resilience Longitudinally (STRADL) family-based cohort, subgroup of the Generation Scotland Scottish Family Health Study, to assess the association between these factors, familial influences, and perivascular space (PVS) characteristics. Using an automated segmentation method on brain magnetic resonance images, we generated PVS volumes, count, density (i.e., count per unit volume), and median length in separate brain regions. Our findings indicate that PVS burden increases with age, hypertension and current depressive symptoms in basal ganglia and centrum semiovale regions, and with higher hair cortisol levels and weaker hand grip only in the centrum semiovale. Regional differences in PVS characteristics observed between the centrum semiovale and basal ganglia could provide insights into the underlying pathophysiology of PVS. Additionally, a familial component was identified, in keeping with a genetic influence on PVS morphology. These results highlight the multifactorial nature of perivascular spaces and emphasize the need for longitudinal studies to observe individual long-term perivascular changes and their impact on brain health.