Mapping the association of cerebral small vessel disease, gray matter integrity and cognitive function

INTRODUCTION: Cerebral small vessel disease (CSVD) is associated with an increased risk of cognitive impairment and dementia. Understanding the brain structural changes associated with CSVD is vital to meet the related health care demands effectively. This study focuses on assessing the integrity of gray matter in relation to CSVD within the general population. METHODS & RESULTS: We examined 2,603 participants (mean age 65 years) from the Hamburg City Health Study, who underwent neuropsychological evaluations and multi-modal neuroimaging. Advanced imaging techniques were used to assess the microstructural and macrostructural integrity of cortical and subcortical gray matter, including the hippocampus. Our findings indicate that the extent of CSVD is associated with abnormalities in gray matter diffusivity, myelin content, and morphology in specific brain regions including the anterior cingulate, insular and temporal cortices, caudate, putamen, pallidum, and hippocampus. Crucially, CSVD-related gray matter abnormalities were linked to cross-domain cognitive performance, represented by the first principal component of multi-domain cognitive test scores. DISCUSSION: Complementing previous research that focuses on CSVD and white matter changes, our study highlights abnormal gray matter integrity as a possible link between small vessel pathology and cognitive disorders. The insights gained can guide diagnostic and therapeutic strategies, supporting the advancement of interventions tailored to mitigate the impact of CSVD.