Associations between neuropsychiatric symptoms and incident Alzheimer’s dementia in men versus women

OBJECTIVE: To examine whether associations between individual neuropsychiatric symptoms (NPS) and incident Alzheimer’s dementia (AD) differ in men versus women. METHODS: Data were acquired from the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set. Two sets of older (≥ 60 years) participants were formed: one of cognitively unimpaired (CU) individuals, and one of participants with mild cognitive impairment (MCI). NPS were assessed using the Neuropsychiatric Inventory Questionnaire. Cox proportional hazards models examined associations between individual NPS and AD incidence separately for each participant set. These models featured individual NPS, sex, NPS by sex interactions as well as a number of covariates. RESULTS: The analysis involved 9,854 CU individuals followed for 5.5 ± 3.8 years and 6,369 participants with MCI followed for 3.8 ± 3.0 years. NPS were comparably associated with future AD in men and women with MCI. Regarding CU participants, the following significant sex by NPS interactions were noted: female sex moderated the risk conferred by moderate/severe apathy (HR = 7.36, 3.25–16.64) by 74%, mitigated the risk conferred by moderate/severe depression (HR = 3.61, 2.08–6.28) by 52%, and augmented the risks conferred by mild depression (HR = 1.00, 0.60–1.68) and agitation (HR = 0.81, 0.40–1.64) by 83% and 243%, respectively. CONCLUSIONS: Apathy, depression and agitation were differentially associated with incident AD in CU men and women. No individual NPS was associated with different risks of future AD in men versus women with MCI. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00415-022-11541-w.