Neuropsychiatric symptoms predict rate of change in executive function in Alzheimer's disease and related dementias

J Int Neuropsychol Soc. 2025 Jan 16:1-10. doi: 10.1017/S1355617724000730. Online ahead of print.

Abstract

Objective: Neuropsychiatric symptoms (NPS) are considered diagnostic and prognostic indicators of dementia and are attributable to neurodegenerative processes. Little is known about the prognostic value of early NPS on executive functioning (EF) decline in Alzheimer's disease and related dementias (ADRD). We examined whether baseline NPS predicted the rate of executive function (EF) decline among older adults with ADRD.

Method: Older adults (n = 1625) with cognitive impairment were selected from the National Alzheimer's Coordinating Center database. EF was estimated with a latent factor indicated by scores on Number Span Backward, Letter Fluency, and Trail Making-Part B. A curve of factors (CUFF) latent growth curve model was estimated to examine rate of change over four years. Baseline NPS severity was entered as a predictor in the model to examine its influence on the rate of change in EF over time.

Results: The CUFF models exhibited good fit. EF significantly declined over four waves (slope = -.16, p < .001). Initial visit NPS severity predicted decline in EF (slope = .013, p < .001), such that those with greater baseline NPS severity demonstrated a more rapid decline in EF performance over time. Presence of 2 NPS significantly predicted EF decline, and those with medium total NPS severity (NPS score of 2-4) at baseline exhibited a sharper decline in EF.

Conclusions: Findings underscore the importance of targeting NPS early across ADRD syndromes to minimize EF decline, offering novel insights into how early NPS treatment may alter cognitive trajectories. We provide an innovative, user-friendly web-based application that may be helpful for personalized treatment planning.

Keywords: Alzheimer’s disease and related dementias; Neuropsychiatric symptoms; executive function; growth curve modeling; longitudinal; mild cognitive impairment.