The Role of Alzheimer’s and Cerebrovascular Pathology in Mediating the Effects of Age, Race, and Apolipoprotein E Genotype on Dementia Severity in Pathologically-Confirmed Alzheimer’s Disease
Affiliations: Department of Psychology, University of Colorado, Colorado Springs, CO, USA
Correspondence:
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Correspondence to: Brandon Gavett, PhD, Department of Psychology, 1420 Austin Bluffs Parkway, Colorado Springs, CO 80918, USA. Tel.: +1 719 255 4135; E-mail: bgavett@uccs.edu
Abstract: Background:Dementia severity can be modeled as the construct δ, representing the “cognitive correlates of functionalstatus.” Objective:We recently validated a model for estimating δ in the National Alzheimer’s Coordinating Center’s Uniform Data Set; however, the association of δ with neuropathology remains untested. Methods:We used data from 727 decedents evaluated at Alzheimer’s Disease (AD) Centers nationwide. Participants spoke English, had no genetic abnormalities, and were pathologically diagnosed with AD as a primary or contributing etiology. Clinical data from participants’ last visit prior to death were used to estimate dementia severity (δ). Results:A structural equation model using age, education, race, and apolipoprotein E (APOE) genotype (number of ɛ2 and ɛ4 alleles) as predictors and latent AD pathology and cerebrovascular disease (CVD) pathology as mediators fit the data well (RMSEA = 0.031; CFI = 0.957). AD pathology mediated the effects of age and APOE genotype on dementia severity. An older age at death and more ɛ2 alleles were associated with less AD pathology and, in turn, with less severe dementia. In contrast, more ɛ4 alleles were associated with more pathology and more severe dementia. Although age and race contributed to differences in CVD pathology, CVD pathology was not related to dementia severity in this sample of decedents with pathologically-confirmed AD. Conclusions:Using δ as an estimate of dementia severity fits well within a structural model in which AD pathology directly affects dementia severity and mediates the relationship between age and APOE genotype on dementia severity.
