Reduced substantia innominata volume mediates contributions of microvascular and macrovascular disease to cognitive deficits in Alzheimer's disease

The relationships between cholinergic system damage and cerebrovascular disease are not entirely understood. Here, we investigate associations between atrophy of the substantia innominata (SI; the origin of cortical cholinergic projections) and measures of large and small vessel disease; specifically, elongation of the juxtaposed internal carotid artery termination and Cholinergic Pathways Hyperintensity scores (CHIPS). The study (n = 105) consisted of patients with Alzheimer's disease (AD) and/or subcortical ischemic vasculopathy, and elderly controls. AD and subcortical ischemic vasculopathy groups showed greater impingement of the carotid termination on the SI and smaller SI volumes. Both carotid termination elongation and CHIPS were associated independently with smaller SI volumes in those with and without AD. Atrophy of the SI mediated effects of carotid termination elongation on language and memory functions and the effect of CHIPS on attention/working memory. In conclusion, SI atrophy was related to cerebrovascular disease of the large and small vessels and to cognitive deficits in people with and without AD.