Neuropathological Correlates of Dementia in Over-80-Year-Old Brain Donors from the Population-Based Cambridge City over-75s Cohort (CC75C) Study

Issue title: Mini-Forum: Clinical-Pathologic Correlations in Population- and Community-Based Studies of Brain Aging

Guest editors: Thomas Montine and Joshua Sonnen

Article type: Research Article

Authors: Brayne, Carol^{a; *;} | Richardson, Kathryn^a; | Matthews, Fiona E.^b | Fleming, Jane^a | Hunter, Sally^a | Xuereb, John H.^c | Paykel, Eugene^d | Mukaetova-Ladinska, Elizabeta B.^e | Huppert, Felicia A.^d | O'Sullivan, Angela^d | Dening, Tom^f | the Cambridge City over-75s Cohort (CC75C) study neuropathology collaboration

Affiliations: [a] Department of Public Health and Primary Care, University of Cambridge, Institute of Public Health, Cambridge, UK | [b] Medical Research Council Biostatistics Unit, Institute of Public Health, Cambridge, UK | [c] Department of Pathology, University of Cambridge, Cambridge, UK | [d] Department of Psychiatry, University of Cambridge, Cambridge, UK | [e] Institute for Ageing and Health, Newcastle University, Wolfson Research Centre, Campus for Ageing and Vitality, Newcastle upon Tyne, UK | [f] Cambridgeshire & Peterborough NHS Foundation Trust, Fulbourn Hospital, Cambridge, UK

Correspondence: [*] Address for correspondence: Carol Brayne, Department of Public Health & Primary Care, University of Cambridge, Institute of Public Health, Robinson Way, Cambridge, CB2 0SR, UK. Tel.: +44 1223 330334; Fax: +44 1223 330330; E-mail: [email protected].

Note: [1] Joint first authors.

Note: [2] CC75C study neuropathology collaboration: Carol Brayne, Tom Dening, Felicia A. Huppert, Rick Hills, Fiona E. Matthews, Elizabeta B. Mukaetova-Ladinska, Angela O’Sullivan, Eugene Paykel, John H. Xuereb.

Abstract: Key neuropathological changes associated with late-onset dementia are not fully understood. Population-based longitudinal studies offer an opportunity to step back and examine which pathological indices best link to clinical state. CC75C is a longitudinal study of the population aged 75 and over at baseline in Cambridge, UK. We report on the first 213 participants coming to autopsy with sufficient information for an end of life dementia diagnosis. Clinical diagnosis was ascertained by examining retrospective informant interviews, survey responses, and death certificates according to DSM-IV criteria. The neuropathological protocol was based on the Consortium to Establish a Registry of Alzheimer's Disease (CERAD). Clinical dementia was present in 113 participants (53%): 67% with Alzheimer's disease, 4% vascular dementia, 22% mixed dementia, and 1% dementia with Lewy bodies. As Alzheimer-type pathology was common, the mutually blinded clinical and neuropathological diagnoses were not strongly related. Multivariable analysis identified associations between dementia during life and entorhinal cortex neuritic plaques, hippocampal diffuse plaques, neocortical neurofibrillary tangles, white matter pallor, Lewy bodies, and hippocampal atrophy. These results were consistent in those with clinical Alzheimer's disease. Vascular pathologies, especially microinfarcts, were more common in those with clinical diagnoses including vascular dementia. Alzheimer-type and cerebrovascular pathology are both common in the very old. A greater burden of these pathologies, Lewy bodies, and hippocampal atrophy, are associated with a higher risk of, but do not define, clinical dementia in old age.

Keywords: Alzheimer's disease, cohort study, dementia, neuropathology, old age, vascular dementia

DOI: 10.3233/JAD-2009-1182

Journal: Journal of Alzheimer's Disease, vol. 18, no. 3, pp. 645-658, 2009