Neuropsychiatric symptoms and cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging: Neuropsychiatry and behavioral neurology: Neuropsychiatric symptoms in MCI and dementia

Background Neuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. However, the association between NPS and global and domain‐specific cognitive trajectories among older adults free of dementia remains unclear. Method We conducted a longitudinal study derived from the population‐based Mayo Clinic Study of Aging, including individuals aged ≥ 50 years who were free of dementia. Participants completed the Neuropsychiatric Inventory Questionnaire at baseline and underwent neuropsychological testing assessing four cognitive domains (i.e., memory, language, attention, visuospatial skills) every 15 months. We calculated linear mixed‐effect models with random subject‐specific intercepts and slopes to examine the association between presence of twelve different NPS (i.e., delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor behavior, nighttime behavior, appetite) at baseline and trajectories for individual yearly change in global and domain‐specific cognitive z‐scores. The models were adjusted for age, sex, education, and whether or not this was the first time the cognitive battery had been administered. Result The sample included 5081 persons (51% males; 4439 cognitively unimpaired, 642 with MCI). The median [IQR] age was 74 [67, 81] years, and the median [IQR] education was 14 [12, 16] years. Regardless of NPS status, participants declined in cognition over time, on average. However, presence of NPS was significantly associated with an increased decline in cognition, i.e., the annualized change in global cognition z‐scores for participants with compared to without the given NPS ranged from ‐0.018 (p = 0.011) for irritability to ‐0.16 (p = 0.001) for hallucinations. These associations between NPS and annual decline in global cognition were significant for all NPS except euphoria and disinhibition. Similar results were seen for the individual cognitive domains, e.g., participants with depression, apathy and nighttime behavior had a greater longitudinal decline in all domain specific z‐scores, whereas presence of delusions and anxiety was associated with a more pronounced decline in language, attention and visuospatial skills. Conclusion Neuropsychiatric symptoms are associated with greater longitudinal decline of both global and domain‐specific cognitive functions in community‐dwelling older adults free of dementia. More research is needed to confirm these preliminary findings.