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Abstract White matter hyperintensities (WMH), which are brain lesions associated with cerebral small vessel disease and aging, signify fiber loss and pruning. Analysis of T2-FLAIR MRI data from the NACC cohort, including cognitively normal (CN), cognitively impaired (CI), and Alzheimer’s disease (CI-AD) subjects, revealed that a significant subset of participants, even those classified as CN, harbor substantial periventricular (PVWMH) and deep white matter hyperintensity (DWMH) loads, while others displayed minimal or no PVWMH and DWMH, across ages 50-94 years. In this study, we quantified the thresholds and progression kinetics of PVWMH and DWMH and their impact on cognitive performance and neuroanatomic changes in the aging cohort (NCN = 521, NCI = 146, NCI-AD = 319). Our findings explore the impact of PVWMH and DWMH loads on global and specific cognitive domains to determine whether cognitive impairments are directly induced by PVWMH and DWMH loads, or mediated through distinct neuroanatomic structures. PV and DWMH loads are higher in CI and CI-AD subjects compared to CN but the PVWMH and DWMH loads are not discriminative of CI and CI-AD. The progression kinetics of PVWMH and DWMH volume with age indicate an exponential rate of increase, with PVWMH escalating approximately twice as fast as DWMH particularly around an inflection point at 61 years of age. PVWMH load presents with increased probability of occurrence in frontal horn compared to occipital horn while DWMH is diffused and accumulates significantly at later age than that observed for PVWMH. Multivariate global regression suggested significant effect (p2.3 mL, significant deficits in TMTs were observed compared to the subjects without PVWMH load. A PVWMH volume >2.3 mL and DWMH >2.75 mL is significantly associated with impairments in attention DWMH less impactful. PVWMH, not DWMH, significantly affects cognitive decline via a unique set of brain structural loss. PVWMH and DWMH loads are not discriminative of CI and AD subjects. Overview
Gupta et al. (Wed,) studied this question.