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Article type: Research Article
Authors: Sharma, Manu J.a; b | Callahan, Brandy L.a; b; *
Affiliations: [a] Department of Psychology, University of Calgary, Calgary (AB), Canada | [b] Hotchkiss Brain Institute, Calgary (AB), Canada
Correspondence: [*] Correspondence to: Brandy L. Callahan, PhD, 2500 University Dr NW, Calgary, Alberta T2N 1N4, Canada. Tel.: +1 403 220 7291; E-mail: brandy.callahan@ucalgary.ca.
Abstract: Background:Mild cognitive impairment (MCI) is considered by some to be a prodromal phase of a progressive disease (i.e., neurodegeneration) resulting in dementia; however, a substantial portion of individuals (ranging from 5–30%) remain cognitively stable over the long term (sMCI). The etiology of sMCI is unclear but may be linked to cerebrovascular disease (CVD), as evidence from longitudinal studies suggest a significant proportion of individuals with vasculopathy remain stable over time. Objective:To quantify the presence of neurodegenerative and vascular pathologies in individuals with long-term (>5-year) sMCI, in a preliminary test of the hypothesis that CVD may be a contributor to non-degenerative cognitive impairment. We expect frequent vasculopathy at autopsy in sMCI relative to neurodegenerative disease, and relative to individuals who convert to dementia. Methods:In this retrospective study, using data from the National Alzheimer’s Coordinating Center, individuals with sMCI (n = 28) were compared to those with MCI who declined over a 5 to 9-year period (dMCI; n = 139) on measures of neurodegenerative pathology (i.e., Aβ plaques, neurofibrillary tangles, TDP-43, and cerebral amyloid angiopathy) and CVD (infarcts, lacunes, microinfarcts, hemorrhages, and microbleeds). Results:Alzheimer’s disease pathology (Aβ plaques, neurofibrillary tangles, and cerebral amyloid angiopathy) was significantly higher in the dMCI group than the sMCI group. Microinfarcts were the only vasculopathy associated with group membership; these were more frequent in sMCI. Conclusion:The most frequent neuropathology in this sample of long-term sMCI was microinfarcts, tentatively suggesting that silent small vessel disease may characterize non-worsening cognitive impairment.
Keywords: Autopsy, cerebrovascular, cognition, dementia, longitudinal, neuropathology
DOI: 10.3233/JAD-200829
Journal: Journal of Alzheimer's Disease, vol. 79, no. 3, pp. 1269-1283, 2021
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