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Impact of Less Common and "Disregarded" Neurodegenerative Pathologies on Dementia Burden in a Population-Based Cohort

Lookup NU author(s): Professor Ian McKeith, Professor Carol Brayne


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Epidemiological studies investigating the pathological bases of late onset dementia focus on classical markers such as plaques and tangles. The significance of pathologies characteristically associated with rare dementia syndromes such as Pick bodies and severe neuronal loss are considered to be well defined. The significance of other pathologies, often accepted as a feature of neurodegenerative syndromes, such as Hirano bodies and gliosis is not clear. This study investigated the significance of these rarer and 'disregarded' pathologies to dementia in the population. A total of 627 individuals aged 71-103 from the Epidemiological CLInicoPathological Studies in Europe (EClipSE) project with clinical dementia status at death determined were assessed. Pathologies assessed included Pick bodies, severe neuronal loss, gliosis, and granulovacuolar degeneration (GVD) in the cortex and/or hippocampus, along with brainstem plaques, tangles, neuronal loss, gliosis, pigmentary incontinence, and Lewy bodies. All pathologies were associated with dementia when controlling for plaques and tangles except Hirano bodies, GVD, and brainstem plaques. These included hippocampal and entorhinal gliosis; cortical, hippocampal, and entorhinal neuronal loss; along with brainstem neuronal loss, gliosis, pigmentary incontinence, Lewy bodies, and tangles. Pick bodies were present in five individuals, all with clinical dementia. These epidemiological data indicate that dementia in old age is associated with a broad range of pathological and anatomical substrates pointing to potential areas for future research, particularly the brainstem.

Publication metadata

Author(s): Keage HAD, Ince PG, Matthews FE, Wharton SB, McKeith IG, Brayne C, MRC CFAS CC75C

Publication type: Article

Publication status: Published

Journal: Journal of Alzheimer's Disease

Year: 2012

Volume: 28

Issue: 2

Pages: 485-493

Print publication date: 01/11/2011

ISSN (print): 1387-2877

ISSN (electronic): 1875-8908

Publisher: IOS Press


DOI: 10.3233/JAD-2011-111268


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Funder referenceFunder name
European Commission at the University of Cambridge
National Institute for Health Research Cambridge BioMedical Research Centre
568890Australian NHMRC