Changes in dementia risk along with onset age of depression: A longitudinal cohort study of elderly depressed patients

Abstract

Background Depression in late-life is linked to an increased risk of Alzheimer's dementia (AD), with the risk potentially varying based on the onset age of depression. Previous research typically dichotomized depression onset age between 55 and 65 years; however, the specific age at which depression onset increases AD risk in older adults remains unclear. In this study, we aimed to investigate the relationship between depression onset age and AD risk and compare characteristics between different onset age groups. Methods A longitudinal cohort of 251 elderly patients diagnosed with major depressive disorder was followed for up to 22 years. Participants were categorized into four groups based on depression onset age: ≤ 54 years, 55–64, 65–74, and ≥ 75 years. Annual cognitive assessments were conducted using the Korean Mini-Mental State Examination, with further neuropsychological testing when cognitive decline was suspected. Cox proportional hazards models were used to assess AD conversion risk across groups, adjusting for covariates. Results During follow-up, 75 patients (29.88%) converted to AD. Depression onset after age 75 was significantly associated with a higher risk of AD conversion (hazard ratio [HR], 8.95; 95% confidence interval [CI], 3.41–23.48; p < 0.0001) and a shorter time to conversion compared to onset before age 55 (40.93 vs. 83.40 months). After adjusting for covariates, depression onset after age 75 remained significantly associated with AD conversion (adjusted HR, 6.07; 95% CI, 1.26–29.34; p = 0.0189). This group also had milder depressive symptoms and a higher prevalence of hypertension and cerebrovascular disease than those with depression onset before age 55. Conclusions Depression onset after age 75 is strongly associated with an increased risk of AD and a shorter time to dementia onset. Individuals with depression onset after age 75 appear more closely linked to vascular comorbidities, while those with depression onset before age 55 are characterized by severe and recurrent depressive episodes. The mechanisms leading to AD in individuals with depression may differ from those without prior depression. Trial registration: The study is registered (NCT01237275, 1994-10-14, Development of A Technique to Predict Antidepressant Responsiveness in Depressive Patients) in ClinicalTrials.gov.