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Associations between multimorbidity and neuropathology in dementia: a case for considering functional cognitive disorders, psychiatric illness, and dementia mimics

Lookup NU author(s): Dr Calum Hamilton, Professor Fiona MatthewsORCiD, Professor Johannes Attems, Dr Paul Donaghy, Dr Daniel ErskineORCiD, Professor John-Paul TaylorORCiD, Professor Alan ThomasORCiD



This is the authors' accepted manuscript of an article that has been accepted and is due to be published in its final definitive form by Cambridge University Press, 2024.

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Background: Multimorbidity, the presence of two or more health conditions, has been identified as a possible risk factor for clinical dementia. It is unclear whether this is due to worsening brain health and underlying neuropathology, or other factors. In some cases, conditions may reflect the same disease process as dementia (e.g. Parkinson’s disease, vascular disease), in others, conditions may reflect a prodromal stage of dementia (e.g. depression, anxiety and psychosis). Aims: We aimed to assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. Method: We examined antemortem and autopsy data from 767 brain tissue donors from the United Kingdom, identifying physical multimorbidity in later life, and specific brain-related conditions. We assessed associations between these purported risk factors and dementia-related neuropathological changes at autopsy (Alzheimer’s disease related neuropathology, Lewy pathology, cerebrovascular disease, and limbic-predominant age-related TDP43 encephalopathy) with logistic models. Results: Physical multimorbidity was not associated with greater dementia-related neuropathological changes. In the presence of physical multimorbidity, clinical dementia was less likely to be associated with Alzheimer’s disease pathology. Conversely, conditions which may be clinical or prodromal manifestations of dementia-related neuropathology (Parkinson’s disease, cerebrovascular disease, depression, and other psychiatric conditions) were associated with dementia and neuropathological changes. Conclusions: Physical multimorbidity alone is not associated with greater dementia-related neuropathological change; inappropriate inclusion of brain-related conditions in multimorbidity measures and misdiagnosis of neurodegenerative dementia may better explain increased rates of clinical dementia in multimorbidity. Data Set Information: Data were drawn from the Brains for Dementia Research study.

Publication metadata

Author(s): Hamilton CA, Matthews FE, Attems J, Donaghy PC, Erskine D, Taylor JP, Thomas AJ

Publication type: Article

Publication status: In Press

Journal: British Journal of Psychiatry

Year: 2024

Acceptance date: 25/01/2024

Date deposited: 25/01/2024

ISSN (print): 0007-1250

ISSN (electronic): 1472-1465

Publisher: Cambridge University Press


Funder referenceFunder name
Alzheimer's Brain Banks UK
Alzheimer's Research UK
NIHR Newcastle Biomedical Research Centre