Neuropsychiatric symptom subtypes and dementia‐associated neuropathologic change

INTRODUCTION Neuropsychiatric symptoms (NPS) are prevalent in clinically diagnosed Alzheimer's disease (AD), yet their etiology remains unclear. We assessed associations between NPS and neuropathologic features in dementia patients. METHODS Logistic regression analyses estimated associations between neuropathologic lesions and retroactively assigned NPS phenotypes (early and late psychosis [EPS, LPS], early and late affective symptoms [EAS, LAS]). RESULTS EPS was associated with Lewy body (odds ratio [OR] = 2.4, p < 0.0001) and white matter (OR = 1.7, p < 0.0001) pathology. LPS was associated with moderate/severe neurofibrillary tangles (OR = 2.8, p < 0.0001), moderate/frequent neuritic plaques (OR = 2.3, p < 0.0001), Lewy bodies (OR = 1.9, p < 0.0001), and cerebral amyloid angiopathy (OR = 1.6, p < 0.0001). EAS was associated with white matter injury (OR = 3.4, p < 0.0001); EAS and LAS were associated with moderate/severe neurofibrillary tangles (ORs = 1.7, 1.9, p < 0.005). Risk for EPS, LPS, and EAS increased with total neuropathologic burden. DISCUSSION NPS subtypes are differentially associated with AD/non‐AD neuropathologic features, suggesting that efficiency of interventional targets may depend upon timing and type of NPS. Highlights Timing/nature of neuropsychiatric symptoms (NPS) had distinct associations with brain autopsy findings in the National Alzheimer's Coordinating Center. Increased odds for psychosis symptoms was associated with both Alzheimer's disease neuropathologic change (ADNC) and Lewy body dementia (LBD). Late psychosis symptoms (PS) was most strongly associated with ADNC, early PS most strongly with LBD. Early PS and affective symptoms were both associated with white matter disease.