Background & Objective: Interactions between small vessel diseases (SVD) and cognitive functions were reported in the previous studies, and these effects were varied according to SVD burden and distributions. Cholinergic pathway has gained attention for its pivotal role to maintain normal cognitive function. We aimed to investigate the associations between SVD burden and distributions of the cholinergic pathways and structural changes of cholinergic innervated cortical/subcortical regions.
Methods: We enrolled patients who were diagnosed as subcortical vascular cognitive impairment (scVCI) from Jan 2010 to Feb 2017 in a university hosptial. Subjects were characterized by moderate to severe white matter hyperintensities (WMH), lacunes, and microbleeds. Cholinergic Pathway HyperIntensities Scale (CHIPS) scores were assessed to quantify the cholinergic pathway disruptions. Cortical thickness and subcortical volumes of cholinergic-innervated structures were quried from volumetric MRI, and analyzed using Freesurfer. Correlation between CHIPS scores and normalized volumetric parameters of cholinergic-innervated structures were investigated.
Result: A total of 80 patients were enrolled. Mean age was 78.4 years (SD 6.5), 59 (73.8%) patients were female, and median level of educations were 6 years (IQR 0.5-11.5). Median MMSE score was 17 (IQR 13-20). Median CHIPS score was 11 points (IQR 7-17, min 0, max 37). Total intracranial volume showed significant relationship with age (r=-0.23, p=0.04) as well as level of education (r=0.36, p=0.001) The CHIPS scores were negatively associated with cortical thickness of inferior temporal cortex (r=-0.26, p=0.02), and showed marginal significance for medial orbitofrontal cortical thickness (r=-0.22, p=0.057) after adjusting for age and level of education. The CHIPS scores were positively associated with subcortical volume of putamen (r=0.37, p=0.001). On the contrary, it was not correlated with other cortical/subcortical structures.
Conclusions: Our study revealed that the disruption of cholinergic pathways in scVCI may accompany the structural changes of innervated cortical/subcortical regions. These findings may shed light on the understanding the pathophysiology of scVCI.