Depressive symptom instability predicts incident mild cognitive impairment and dementia in older adults

INTRODUCTION: Neuropsychiatric symptoms frequently precede Alzheimer's disease and related dementias, yet risk prediction models typically rely on baseline depression severity or diagnostic status. We examined whether instability in depressive symptoms predicted incident mild cognitive impairment (MCI) or dementia. METHODS: Data were drawn from 11,951 older adults enrolled across 42 US Alzheimer's Disease Research Centers and followed for up to 19 years. Depressive symptoms were assessed using the Geriatric Depression Scale and characterized using rule-based groupings and latent class trajectories. The Structured Life-Course Modeling Approach (SLCMA) was used to compare four competing temporal hypotheses of risk. Cox models adjusted for demographic factors and apolipoprotein E (APOE) ε4 status. RESULTS: Fluctuating depressive symptom trajectories were associated with increased risk of incident cognitive impairment. Symptom instability showed the lowest prediction error in exploratory SLCMA analyses. DISCUSSION: Instability in depressive symptoms may represent an early and clinically accessible risk marker for MCI and dementia.