title: Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons.
abstract: We evaluated the association between mini-mental status examination (MMSE) scores proximal to death and the values of 43 different clinical and pathological parameters. Studies were performed using data from 334 elderly, longitudinally evaluated research subjects who had undergone autopsy and satisfied inclusion criteria from an initial study group of 501. Interindividual variance in MMSE scores was used as a surrogate for the severity of cognitive impairment linked to aging (CILA). A statistical linear regression-based model provided a framework for assessing the parameters with significant, direct impact on CILA severity. Strong association between CILA and Alzheimer's disease (AD) pathology, especially isocortical neurofibrillary tangles, was evident. The pattern of association between AD lesion densities with cognitive impairment severity was biologically informative, with neuritic plaques having more impact in relatively high-functioning individuals. Abundant isocortical Lewy bodies tended to be an additive pathology correlating with final MMSE scores approximately 10 points lower. In a subset of cases we found evidence for association between TDP-43-related pathology and CILA severity, independent of AD or hippocampal sclerosis. There was no support for independent association between CILA severity and most evaluated indices including diffuse plaques, argyrophilic grains, heart disease, education level, apolipoprotein E alleles or diabetes.
authors.affiliation: Department of Pathology and Division of Neuropathology, University of Kentucky Medical Center, Sanders-Brown Center on Aging and Alzheimer's Disease Center, University of Kentucky, Lexington, KY, USA. pnels2@email.uky.edu
authors.forename: Peter T
authors.initials: PT
authors.lastname: Nelson
authors.forename: Erin L
authors.initials: EL
authors.lastname: Abner
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Schmitt
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Kryscio
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Jicha
authors.forename: Charles D
authors.initials: CD
authors.lastname: Smith
authors.forename: Daron G
authors.initials: DG
authors.lastname: Davis
authors.forename: John W
authors.initials: JW
authors.lastname: Poduska
authors.forename: Ela
authors.initials: E
authors.lastname: Patel
authors.forename: Marta S
authors.initials: MS
authors.lastname: Mendiondo
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology / Q000523:psychology; D000544:Alzheimer Disease / Q000473:pathology; D001057:Apolipoproteins E / Q000378:metabolism; D001344:Autopsy; D001921:Brain / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D003072:Cognition Disorders / Q000473:pathology* / Q000523:psychology; D015331:Cohort Studies; D004268:DNA-Binding Proteins / Q000378:metabolism; D016208:Databases, Factual; D005260:Female; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016014:Linear Models; D008297:Male; D015233:Models, Statistical; D009483:Neuropsychological Tests
chemical_list: D001057:Apolipoproteins E; D004268:DNA-Binding Proteins