Exploring the impact of white matter hyperintensities on gray matter atrophy and cognitive decline

White matter hyperintensities (WMHs) are linked to gray matter volume (GMV) and cognitive abilities in Alzheimer's disease (AD). However, the detailed patterns of how WMHs affect brain structure and cognition in AD require more study. We examined 42 AD patients, 54 with mild cognitive impairment, and 59 normal controls. Using various correlation analyses, we explored the relationships between WMHs, GMV, and cognitive function. The findings indicate that WMHs significantly influence brain atrophy in AD, with total WMHs volume, subcortical WMHs volume, and the largest single WMH volume having the most impact. Subcortical WMHs volume notably affected Instrumental Activities of Daily Living scores, while the largest WMH volume influenced cognitive measures. These results highlight that specific WMH subtypes, especially subcortical volume and large lesions, play a pivotal role in GMV atrophy and cognitive decline in AD. our results support a neurovascular mechanism driving neurodegeneration, emphasizing the importance of early interventions targeting vascular issues to slow AD progression. Key points: The study investigated specific subtypes of white matter hyperintensities, revealing their impact on gray matter atrophy and cognitive decline, to identify potential biomarkers for Alzheimer's disease progression.