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Neurobiol Aging. 2018 Jun;66:23-31. doi: 10.1016/j.neurobiolaging.2018.01.025. Epub 2018 Feb 10.

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

Author information

1
Department of General Internal Medicine (Postgraduate), University of Toronto, Ontario, Canada.
2
Heart and Stroke Foundation Canadian Partnership for Stroke Recovery (Sunnybrook site), Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Pharmacology & Toxicology, University of Toronto, Toronto, Ontario, Canada; Cardiac Rehabilitation Program, University Health Network - Toronto Rehabilitation Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada. Electronic address: w.swardfager@utoronto.ca.
3
Heart and Stroke Foundation Canadian Partnership for Stroke Recovery (Sunnybrook site), Sunnybrook Research Institute, Toronto, Ontario, Canada; LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
4
Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
5
Neurology Service, University Health Network - Toronto Rehabilitation Institute, Toronto, Ontario, Canada.
6
Department of Psychiatry and Medical Psychology, Federal University of São Paulo, São Paulo, Brazil.
7
Department of Neurology, McMaster University, Hamilton, Ontario, Canada.
8
Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada; Department of Psychology, University of Toronto, Toronto, Ontario, Canada.
9
Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Imaging & Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
10
LC Campbell Cognitive Neurology Research Unit, Sunnybrook Research Institute, Toronto, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery (Sunnybrook site), Sunnybrook Research Institute, Toronto, Ontario, Canada; Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medicine, Division of Neurology, University of Toronto, Toronto, Ontario, Canada.

Abstract

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.

KEYWORDS:

Alzheimer's disease; Cerebrovascular disorders; Internal carotid artery diseases; Substantia innominata; Vascular dementia

[Indexed for MEDLINE]

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