Periventricular and Deep White Matter Hyperintensity Beyond a Threshold Impairs Unique Cognitive Domains and Neuroanatomic Health

Motivation: While segmenting and quantifying T2-FLAIR-MRI of aging cohorts, it was intriguing to observe that a subset of participants, even those classified as cognitively-normal, harbor substantial Periventricular and Deep White matter hyperintensity (PVWMH and-DWMH), while others displayed minimal/no WMH. Goal(s): To determine the threshold and kinetics of cerebral-small-vessel-disease load as PVWMH and DWMH volumes that lead to impaired cognitive-performance and neuroanatomic-health with-aging. Approach: PVWMH, DWMH, and neuroanatomic volumes of 389 cognitively-normal-subjects were quantified using T2-FLAIR and T1w-MRI. Age-adjusted cognitive-score were examined at WMH-quartiles. Results: PVWMH >2.3ml led to deficits in attention, executive-function and semantic-memory, alongwith structural-atrophy in specific brain-regions; while DWMH had minimal cognitive-impact. Impact: This study quantitatively establishes critical volumetric thresholds of periventricular and deep white matter hyperintensities, beyond which accelerated decline in cognitive performance and neuroanatomic volume is observed. This unique approach establishes clinical implications of cerebral small vessel health and cognitive status.