Clinical Manifestations

Neuropsychiatric symptoms (NPS) are integral to Alzheimer's disease (AD) yet often go under-recognized, despite their profound impact on disease progression, patient outcomes, and care strategies.

A systematic search was conducted in PubMed, EMBASE, SCOPUS, Ovid, and Web of Science up to January 19, 2025. Studies were included if they were original research with a cross-sectional or longitudinal design, involving patients with probable or possible AD diagnosed according to DSM-IV or NINCDS-ADRDA criteria, and reported the prevalence of NPS. The inverse variance method and Freeman-Tukey double arcsine transformation were used for the proportion analysis. For the odds ratio analysis, the inverse variance method (random effects model) was used with tau^2 estimated by the restricted maximum-likelihood estimator (RLE) and confidence intervals (CI) via Q-Profile.

In our meta-analysis of neuropsychiatric symptoms in Alzheimer's disease (AD), we analyzed 400 studies with 3,189,267 observations and 306,880 events. The individual symptoms in decreasing order of their proportion were: Apathy (0.4748 [0.3875; 0.5630]), Irritability (0.4120 [0.3612; 0.4636]), Depression/Dysphoria (0.3802 [0.3253; 0.4366]), Agitation (0.3304 [0.2756; 0.3877]), and Anxiety (0.3072 [0.2541; 0.3629]). There was substantial heterogeneity across studies (I^2 = 99.9%). For deriving pooled odds ratios we analyzed 125 studies with a total of 266,938 observations for the odds ratio. None of the individual symptoms had a significant association. Aberrant motor behavior exhibited the highest association with AD (OR = 12.90 [0.63, 262.46]), followed by wandering (OR = 2.70 [0.06, 128.85]), psychosis (OR = 1.81 [0.37, 8.82]), delusions (OR = 1.52 [0.67, 3.44]), and apathy (OR = 1.33 [0.57, 3.12]). Substantial heterogeneity was observed (I² = 97.4%).

Our meta-analysis reveals that the most prevalent neuropsychiatric symptoms in Alzheimer's disease are apathy, irritability, and depression/dysphoria, with substantial heterogeneity across studies.