Neuropathologic Correlates of Cognition in a Population-Based Sample

Article type: Research Article

Authors: Cholerton, Brenna^{a; c; *} | Larson, Eric. B.^{d; f} | Baker, Laura D.^g | Craft, Suzanne^g | Crane, Paul K.^d | Millard, Steven P.^b | Sonnen, Joshua A.^e | Montine, Thomas J.^e

Affiliations: [a] Geriatric Research, Education, & Clinical Center, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA | [b] Mental Health Service, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA | [c] Department of Psychiatry & Behavioral Science, University of Washington School of Medicine, Seattle, WA, USA | [d] Department of Medicine, University of Washington School of Medicine, Seattle, WA, USA | [e] Department of Pathology, University of Washington School of Medicine, Seattle, WA, USA | [f] Group Health Research Institute, Seattle, WA, USA | [g] Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA

Correspondence: [*] Correspondence to: Brenna Cholerton, PhD, VA Puget Sound Health Care System (GRECC-A-182), 9600 Veterans Drive SW, Tacoma, WA 98493, USA. Tel.: +1 253 583 2032; Fax: +1 253 589 4073; E-mail: bchol@u.washington.edu.

Abstract: Many cognitively normal older adults have underlying neuropathologic changes of Alzheimer's disease (AD), vascular brain injury (VBI), or Lewy body disease (LBD), which confer an increased risk of dementia. The current study focused on the association between multiple neuropathologic indices and performance on specific cognitive domains in a community sample of older adults. Of 438 participants in the Adult Changes in Thought population-based study of brain aging who were autopsied, 363 subjects had cognitive testing at their final study visit and were included. Associations were measured between performance on the Cognitive Abilities Screening Instrument prior to death and neuropathologic endpoints, including AD neuropathologic changes, LBD, cerebral amyloid angiopathy, and measures of VBI. Braak stage for neurofibrillary tangles, lower brain weight, and VBI as measured by cerebral cortical microvascular lesions (μVBI) explained a significant proportion of the variance associated with global cognitive test performance (R2 = 0.31, p < 0.0001) both in the entire sample and when analysis was restricted to non-demented subjects (R2 = 0.23, p < 0.0001). Specific cognitive domains were differentially related to neuropathologic lesion type: memory and executive function with AD pathologic changes and cortical μVBI, executive function with subcortical μVBI, and visuospatial construction with LBD. Thus, neuropathologic lesions of LBD and μVBI are associated with poorer cognitive performance over and above AD neuropathologic changes in subjects without dementia in this cohort. These findings underscore that cognitive impairment is a complex convergent trait that has important implications for clinical investigation and medical management of older adults.

Keywords: Alzheimer's disease, brain, cerebrovascular disorders, cognition, dementia, Lewy bodies, pathologic processes

DOI: 10.3233/JAD-130281

Journal: Journal of Alzheimer's Disease, vol. 36, no. 4, pp. 699-709, 2013