Cognitive impairment in older people has a variety of underlying causes. In addition to neurodegenerative causes such as Alzheimer's disease, a dementia-like cognitive disorder may appear due to non-degenerative factors. Multimorbidity has been previously associated with clinical dementia risk, though whether this was due to greater risk of dementia-related neuropathology, or other factors that mimic dementia, was unclear.  We provide evidence that physical multimorbidity is not associated with greater pathological changes at autopsy. Other factors related to multimorbidity and cognitive impairments may be important targets for investigation, such as functional cognitive disorders, primary psychiatric disorders (depression, anxiety, psychosis) and polypharmacy

Attems, Johannes

Donaghy, Paul C

Hamilton, Calum A

Matthews, Fiona E

Taylor, John-Paul

Thomas, Alan J

English

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 To assess whether multimorbidity in later life was associated with more severe dementia-related neuropathology at autopsy. Method We examined ante-mortem and autopsy data from 767 brain tissue donors from the UK, 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 body pathology, cerebrovascular disease and limbic-predominant age-related TDP-43 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 multimorbidit

Matthews, Fiona E.

Taylor, John Paul

Erskine, Daniel

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Associations between multimorbidity and neuropathology in dementia: Consideration of functional cognitive disorders, psychiatric illness and dementia mimics

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

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

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