Modeling the association between 43 different clinical and pathological variables and the severity of cognitive impairment in a large autopsy cohort of elderly persons

Peter T. Nelson, Erin L. Abner, Frederick A. Schmitt, Richard J. Kryscio, Gregory A. Jicha, Charles D. Smith, Daron G. Davis, John W. Poduska, Ela Patel, Marta S. Mendiondo, William R. Markesbery

Research output: Contribution to journalArticlepeer-review

181 Scopus citations

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.

Original languageEnglish
Pages (from-to)66-79
Number of pages14
JournalBrain Pathology
Volume20
Issue number1
DOIs
StatePublished - Jan 2010

Keywords

  • ApoE
  • Cognition
  • DLB
  • Hippocampal sclerosis
  • Human
  • Stroke

ASJC Scopus subject areas

  • General Neuroscience
  • Pathology and Forensic Medicine
  • Clinical Neurology

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