The effect of ischemic cholinergic damage on cognition in patients with subcortical vascular cognitive impairment

Prior research has shown that the total amount of white matter ischemia had no significant correlation with cognitive deficits. We compared the association of white matter hyperintensities (WMHs) of total as well as cholinergic pathways with clinical dementia severity and investigated whether cholinergic ischemic burden had an independent predictive value with respect to cognitive decline in subcortical vascular cognitive impairment (SVCI). Forty-eight patients underwent detailed neuropsychological tests and brain magnetic resonance imaging. Quantification of WMH in the total white matter and in cholinergic pathways was achieved using the visual Scheltens scale and Cholinergic Pathway HyperIntensity Scale (CHIPS), respectively. We explored the association between WMH scores and clinical dementia rating scale (CDR). To assess the relation between WMH and cognitive scores, multiple linear regression analysis was used. The CHIPS score was higher in subcortical vascular dementia compared to subcortical vascular MCI, while this difference was not found with the total TMHs (TWMH) score. The TWMH score had a positive correlation with CHIPS, however only CHIPS scores positively correlated with sum of box scores of CDR scale (CDR SB; ρ = .474, P = .001). Higher CHIPS scores were associated with lower performance on the semantic word fluency test (β = -.447, P = .036), whereas the TWMH scores had no independent predictive value with respect to cognitive impairment, after controlling for CHIPS score. Our data confirmed the association of ischemic damage within cholinergic pathways with dementia severity, independent of TWMH in SVCI. In addition, this cholinergic deficit is clinically relevant to cognitive deterioration, especially with frontal dysfunction.