Neuropathological correlates of neuropsychiatric symptoms in the Brains for Dementia Research study

Abstract

AbstractBackgroundNeuropsychiatric symptoms are a common feature of many dementia syndromes, and are frequently associated with poor clinical prognosis, reduction in quality of life, earlier institutionalisation, greater disability, and increased caregiver distress, particularly during later stages of disease. It has also been postulated that NPS may occur during prodromal stages of dementia, preceding or alongside early cognitive symptoms. Clinical profiles of dementia are both heterogenous and intersecting, which may reflect that up to 90% of cases have multiple pathologies post‐mortem. Comprehensive clinicopathological studies of neuropsychiatric symptoms in dementia are lacking, thus this study sought to investigate potential neuropsychiatric profiles resulting from mixed underlying pathology.MethodThis analysis aimed to identify pathological correlations of neuropsychiatric symptoms and included 840 post‐mortem brains donated to the Brains for Dementia Research project, a longitudinal study with post‐mortem neuropathological assessment across several brain banks, between 2008 and 2020. Patterns of neuropsychiatric symptoms were compared between pathology subtypes using clinical data including the Neuropsychiatric Inventory (NPI‐Q) and Clinical Dementia Rating scale, and neuropathological assessment of degenerative pathologies and vascular features. Confirmatory factor analysis was used to identify latent variables for psychosis, mood, and behaviour. Associations between pathological variables assessed at autopsy and neuropsychiatric features during life were explored using bivariate and multivariate statistical methods.ResultAlmost 80% of the 494 dementia cases included had at least one neuropsychiatric symptom across the course of disease. Apathy (51.2%) and aggression (41.7%) were the most prevalent neuropsychiatric features across all dementia subtypes. Preliminary results indicate that different underlying pathologies, including neurodegenerative pathologies (amyloid, neurofibrillary tangles, Lewy bodies, TDP‐43 inclusions) and vascular features may be associated with increased likelihood of specific neuropsychiatric symptoms, such as psychosis, mood and behaviour, during life. Co‐occurring substantial AD and Lewy body pathology was associated with the presence of anxiety, depression, and aberrant motor activity during life. AD in the absence of substantial Lewy body pathology, was associated with agitation, apathy, and disinhibition. Lewy body pathology, in the absence of substantial AD pathology, was associated with hallucinations, depression and sleep disturbances.ConclusionThe interaction of multiple pathologies may contribute to differing neuropsychiatric profiles during life.