P1-220: History of depression and risk of hippocampal atrophy and future Alzheimer’s disease

Abstract

Depression may increase risk of Alzheimer's disease (AD) but explanations for underlying mechanisms are still not well understood. One of the hypotheses is that prolonged exposure to glucocorticoids with repeated depressive episodes may lead to hippocampal atrophy and AD. To determine whether history and frequency of depressive episodes increase risk of hippocampal atrophy and incident AD. Participants were 511 persons, aged 60–90 years at baseline and without dementia, from the population–based Rotterdam Scan Study. At baseline, participants reported their history of depressive episodes and, if relevant, the number of episodes. Volumetric assessment of the hippocampus was performed using a 3–dimensional MRI sequence. Total hippocampal volumes were calculated with correction for head size and gender. Subjects with volumes below the 25th percentile of the distribution were defined as having a small hippocampus (n=128). All subjects were followed for development of AD. The diagnosis of AD was made according to internationally accepted criteria. A history of depressive episodes was reported by 142 (27.8%) subjects, with 85 reporting one episode and 50 reporting 2 or more episodes. Logistic regression analyses adjusted for age, gender, education, memory complaints, and MMSE score, showed that subjects with a history of depression were less likely to have a small hippocampus than those without such a history (OR 0.63; 95%CI 0.38–1.05). The OR of having a small hippocampus associated with 1 episode versus none was 0.74 (95%CI 0.41–1.33) and 2+ versus none 0.42 (95%CI 0.18–0.98) (p–trend 0.03). After an average of 6 years of follow–up, 34 subjects developed AD. Cox regression analyses with adjustment for the same covariates showed that subjects with a history of depression had an increased risk of AD (HR 2.42; 95%CI 1.15–5.10). The HR of AD associated with 1 episode versus none was 2.14 (95%CI 0.81–5.64), and 2+ versus none 2.54 (95%CI 0.90–7.16) (p–trend 0.04). This study suggests that elderly with a history of depressive episodes are less likely to have a small hippocampus, whereas prospectively they have an increased risk of AD. If replicated, future research should investigate what mechanisms may underly these seemingly contradictory associations.