Variability in Depressive Symptoms Predicts Cognitive Decline in Age-Related Macular Degeneration

Objective: The measurement of affective symptoms in older persons who decline cognitively is uncertain. The authors investigated whether mood variability predicts dementia in patients with age-related macular degeneration (AMD). Design: Three-year observational study after a clinical trial. Setting: Community follow-up of outpatients ascertained from retina clinics. Participants: One hundred sixty patients with AMD. Measurements: Geriatric Depression Scale (GDS) administered every 2 weeks for 6 months to subjects; Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE) administered to subjects' knowledgeable informants. Results: Twenty-three subjects (14.4%) declined cognitively. Age, education, baseline GDS score ≥5, and variability in GDS scores (i.e., fluctuations between adjacent time points) were associated with cognitive decline. For GDS variability, each 1 unit increase in the residual standard deviation (SD) of the GDS increased the risk for cognitive decline by 93% (IDR = 1.92; 95% CI [1.27–2.91]). Thus, subjects with a residual SD of 1 were nearly twice as likely to become demented as subjects with no variability in GDS scores. The risk for subjects with SDs of 2 increased more than threefold (IDR = 3.68; 95% CI [1.61–8.47]). A multiple regression analysis showed that GDS variability was a significant risk factor for dementia after controlling for significant covariates. Conclusion: These data suggest a useful approach to conceptualizing and measuring depressive symptoms in older persons. Variability in self-reported mood may be an early sign of dementia and may offer new insights into the neurobiological mechanisms linking depression and cognition.