Neuropsychiatric symptoms as predictors of progression to Alzheimer's disease in mild cognitive impairment: A comparative meta-analysis of apathy, depression, and anxiety.
TL;DR
Apathy is a robust and consistent behavioral predictor of progression from MCI to clinical AD dementia, and domain-specific neuropsychiatric assessment may improve future risk stratification.
Abstract
Background
Identifying mild cognitive impairment (MCI) patients at high risk for Alzheimer's disease (AD) is a priority. The independent prognostic utility of neuropsychiatric symptoms (NPS) remains debated.
Methods
We systematically searched longitudinal cohort studies that evaluated the predictive role of baseline apathy, depression, and anxiety for progression from MCI to clinical AD dementia. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using random-effects models with Hartung-Knapp adjustment.
Results
Twenty-two studies (346,185 MCI patients) were included. Apathy demonstrated a statistically significant predictive association with progression (HR = 2.57, 95% CI: 1.58-4.17, p = 0.003). Depression was not significantly associated with progression overall (HR = 1.32, 95% CI: 0.69-2.50). In pre-specified subgroup analyses, a significant association was observed only among studies with follow-up ≥ 3 years (HR = 2.20, 95% CI: 1.08-4.46), although the test for subgroup differences did not reach conventional significance. Anxiety was not significantly associated with progression risk (HR = 1.27).
Conclusion
Apathy is a robust and consistent behavioral predictor of progression from MCI to clinical AD dementia. Depression may represent a potential long-term risk pattern, whereas anxiety requires further validation. Domain-specific neuropsychiatric assessment may improve future risk stratification.