To examine the association between mild behavioral impairment (MBI), neuropsychiatric symptoms (NPS), and postmortem AD and cerebrovascular neuropathology.

NPS are frequently observed in AD and related dementias. We have reported associations of NPS, including MBI, with cognitive and biomarker measures. We sought to extend our study to the outcome of postmortem neuropathology.

This study included 522 participants from a prospective population-based cohort, whose last visit was within 5 years of death, with NPS data (Neuropsychiatric Inventory Questionnaire [NPI-Q], Beck Depression Inventory II [BDI], Beck Anxiety Inventory [BAI]), AD neuropathology data (Braak stage, Thal phase, CERAD neuritic plaques score), and cerebrovascular neuropathology data (Kalaria score). Linear regression models were used for the outcomes of Braak and Kalaria. Proportional odds logistic regression models were run for the outcomes of Thal and CERAD. Models were run using number of visits with NPS present (adjusted for total number of visits), MBI TTV (defined as having MBI based on NPI-Q for at least two-thirds of study visits [TTV] for those with 2+ visits), and with each NPI-Q (present/absent) variable, BDI, BAI, and MBI (defined as having at least one NPI-Q variable indicated) at last visit before death as predictors. All models were adjusted for age at last visit, sex, and education.

Mean (SD) age was 86.2 (6.3) years at last visit; 42% were female. Having MBI TTV was associated with higher CERAD (OR=1.60, 95%CI=1.09-2.35) and higher Thal (OR=1.55, 95%CI=1.03-2.32). Number of visits with NPS and MBI status at last visit only were both associated with higher Braak, CERAD, and Thal scores. The latter varied by specific NPS considered. No associations of MBI/NPS were observed with Kalaria.

MBI/NPS are associated with the neuropathological measures of Braak, CERAD, and Thal, but not Kalaria, suggesting they might be more related to AD than cerebrovascular neuropathology.