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

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.