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

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