Natural Evolution and Heterogeneity of Neuropsychiatric Symptoms Across Neurocognitive Disorders: A Systematic Review and Meta-Analysis of Longitudinal Studies

Int J Geriatr Psychiatry. 2025 Oct;40(10):e70169. doi: 10.1002/gps.70169.

ABSTRACT

OBJECTIVES: Neuropsychiatric symptoms (NPS) are common and burdensome manifestations of neurocognitive disorders but the characterization of their natural evolution over time is limited. We conducted a systematic review and meta-analysis to describe the longitudinal progression and heterogeneity of NPS across Alzheimer’s disease (AD), Lewy body dementia (LBD), and frontotemporal dementia (FTD).

METHODS: We systematically reviewed observational longitudinal studies published between 2000 and 2024 assessing the prevalence or severity of NPS at ≥ 2 time points using validated instruments. Random-effects meta-analyses were performed to pool changes in prevalence (risk difference) and severity (standardized mean difference [SMD]) at short-term (< 12 months), mid-term (12 to < 24 months), and long-term (≥ 24 months) follow-up. Heterogeneity and publication bias were also assessed. Subgroup analyses were conducted by type of neurocognitive disorder.

RESULTS: We included 26 studies comprising 5509 participants. Apathy was the most prevalent NPS at baseline (45%), followed by irritability (35%) and depression (35%). Over time, most NPS demonstrated progressive increases in prevalence, with agitation (+16%) and apathy (+15%) emerging most frequently at long-term follow-up. Severity of most NPS remained stable, except for apathy and aberrant motor behavior, which increased significantly, and sleep disturbances, which improved. Global NPS burden increased significantly at long-term (SMD +2.04). Heterogeneity of trajectories was notably high and varied across symptoms and disorders. Subgroup analyses in AD confirmed increases in apathy, delusions, and hallucinations over time.

CONCLUSIONS: NPS exhibit distinct and heterogeneous longitudinal patterns in neurocognitive disorders. Greater understanding of these trajectories may inform clinical management, prognostication, and the timing of interventions.

PMID:41117129 | DOI:10.1002/gps.70169