Periventricular White Matter Hyperintensity Prunes the Resting State Connectivity of Default Mode Network with Aging

Motivation: Default-Mode-Network (DMN) connectivity, central for memory, attention, and executive-functions, may get disrupted with accumulation of Cerebral-small vessel-disease load as Periventricular and deep-white-matter-hyperintensity (PVWMH-and-DWMH) volume beyond a threshold, impacting cognition. Goal(s): To quantify whether PVWMH/DWMH alters DMN functional connectivity, accelerating cognitive decline compared to age-matched healthy individuals without WMH. Approach: Seed-based network-analysis of DMN-regions (PCC, mPFC, LP) was conducted with aging in ADNI cohort of normal aging subjects, alongside PVWMH/DWMH segmentation and quantification. Results: DMN remains intact in subjects without PVWMH; however, PVWMH >5 ml at age >75 years disrupts DMN, suggesting WMH mediates cognitive-impairments via impaired resting-state networks with progression in age. Impact: This study reveals a threshold of periventricular white matter hyperintensity impacting default mode network connectivity with age, highlighting WMH load's role in disrupting connectivity. Resting-state network health and WMH load are essential for understanding cognitive aging trajectories.