Brain Region Mapping and Quantification of White Matter Hyperintensity: Estimating the Direct and Indirect impact of WMH Load on Cognition

Motivation: Understanding the magnitude and threshold of PVWMH and DWMH that disrupt cognitive abilities in MCI and AD, compared to healthy aging. Goal(s): To investigate white matter hyperintensity distribution & its impact on cognitive functions. Approach: Neuroanatomic segmentation & quantification of Periventricular WMH and DeepWMH, with mediation analysis assessing their impact on cognitive functionsResults: WMH load accrues vascular insult to brain structures, which in-turn mediates impaired cognitive functions, specifically motor and executive functions. WMH load in periventricular region abrogates the information processing and processing speed indirectly mediated through paracentral gyrus thickness, rostral middle frontal volume and lingual gyrus thickness. Impact: Periventricular white matter hyperintensity progresses faster compared to DeepWMH with Aging. We establish that the Regional Distribution of DeepWMH load is distinct for CN, MCI and AD. High WMH load impairs Executive memory and Motor Memory via specific structural atrophy.