Early Depressive Symptoms Predict Faster Dementia Progression in Autosomal-Dominant Alzheimer’s Disease

BACKGROUND: Depression is associated with Alzheimer's disease (AD). OBJECTIVE: To evaluate the association between depressive symptoms and age of onset of cognitive decline in autosomal dominant AD, and to determine possible factors associated to early depressive symptoms in this population. METHODS: We conducted a retrospective study to identify depressive symptoms among 190 presenilin 1 (PSEN1) E280A mutation carriers, subjected to comprehensive clinical evaluations in up to a 20-year longitudinal follow-up. We controlled for the following potential confounders: APOE, sex, hypothyroidism, education, marital status, residence, tobacco, alcohol, and drug abuse. RESULTS: PSEN1 E280A carriers with depressive symptoms before mild cognitive impairment (MCI) develop dementia faster than E280A carriers without depressive symptoms (Hazard Ratio, HR = 1.95; 95% CI, 1.15-3.31). Not having a stable partner accelerated the onset of MCI (HR = 1.60; 95 % CI, 1.03-2.47) and dementia (HR = 1.68; 95 % CI, 1.09-2.60). E280A carriers with controlled hypothyroidism had later age of onset of depressive symptoms (HR = 0.48; 95 % CI, 0.25-0.92), dementia (HR = 0.43; 95 % CI, 0.21-0.84), and death (HR = 0.35; 95 % CI, 0.13-0.95). APOEɛ2 significantly affected AD progression in all stages. APOE polymorphisms were not associate to depressive symptoms. Women had a higher frequency and developed earlier depressive symptoms than men throughout the illness (HR = 1.63; 95 % CI, 1.14-2.32). CONCLUSION: Depressive symptoms accelerated progress and faster cognitive decline of autosomal dominant AD. Not having a stable partner and factors associated with early depressive symptoms (e.g., in females and individuals with untreated hypothyroidism), could impact prognosis, burden, and costs.