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Insights into the pathological basis of dementia from population-based neuropathology studies

Wharton, Stephen B.; Simpson, Julie E.; Ince, Paul G.; Richardson, Connor D.; Merrick, Richard; Matthews, Fiona E.; Brayne, Carol

Authors

Stephen B. Wharton

Julie E. Simpson

Paul G. Ince

Connor D. Richardson

Richard Merrick

Carol Brayne



Abstract

The epidemiological neuropathology perspective of population and community-based studies allows unbiased assessment of the prevalence of various pathologies and their relationships to late-life dementia. In addition, this approach provides complementary insights to conventional case–control studies, which tend to be more representative of a younger clinical cohort. The Cognitive Function and Ageing Study (CFAS) is a longitudinal study of cognitive impairment and frailty in the general United Kingdom population. In this review, we provide an overview of the major findings from CFAS, alongside other studies, which have demonstrated a high prevalence of pathology in the ageing brain, particularly Alzheimer's disease neuropathological change and vascular pathology. Increasing burdens of these pathologies are the major correlates of dementia, especially neurofibrillary tangles, but there is substantial overlap in pathology between those with and without dementia, particularly at intermediate burdens of pathology and also at the oldest ages. Furthermore, additional pathologies such as limbic-predominant age-related TDP-43 encephalopathy, ageing-related tau astrogliopathy and primary age-related tauopathies contribute to late-life dementia. Findings from ageing population-representative studies have implications for the understanding of dementia pathology in the community. The high prevalence of pathology and variable relationship to dementia status has implications for disease definition and indicate a role for modulating factors on cognitive outcome. The complexity of late-life dementia, with mixed pathologies, indicates a need for a better understanding of these processes across the life-course to direct the best research for reducing risk in later life of avoidable clinical dementia syndromes.

Citation

Wharton, S. B., Simpson, J. E., Ince, P. G., Richardson, C. D., Merrick, R., Matthews, F. E., & Brayne, C. (2023). Insights into the pathological basis of dementia from population-based neuropathology studies. Neuropathology and Applied Neurobiology, 49(4), Article e12923. https://doi.org/10.1111/nan.12923

Journal Article Type Review
Acceptance Date Jun 29, 2023
Online Publication Date Jul 18, 2023
Publication Date Aug 1, 2023
Deposit Date Jan 21, 2024
Publicly Available Date Jan 25, 2024
Journal Neuropathology and Applied Neurobiology
Print ISSN 0305-1846
Electronic ISSN 1365-2990
Publisher British Neuropathological Society
Peer Reviewed Peer Reviewed
Volume 49
Issue 4
Article Number e12923
DOI https://doi.org/10.1111/nan.12923
Keywords Alzheimer's disease; Dementia neuropathology; Epidemiological neuropathology; Lewy body disease; Population-representative neuropathology; Vascular dementia
Public URL https://hull-repository.worktribe.com/output/4496268

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Publisher Licence URL
http://creativecommons.org/licenses/by/4.0

Copyright Statement
© 2023 The Authors. Neuropathology and Applied Neurobiology published by John Wiley & Sons Ltd on behalf of British Neuropathological Society.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.




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