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History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease

From Julius Center for Health Sciences and Primary Care (M.I.G.), University Medical Center Utrecht; and Departments of Epidemiology and Biostatistics (M.I.G., T.d.H., A.H., M.M.B.B.) and Neurology (T.d.H., P.J.K.), Erasmus Medical Center, Rotterdam, The Netherlands.

Address correspondence and reprint requests to Dr. Monique M.B. Breteler, Dept. of Epidemiology & Biostatistics, Erasmus Medical Center, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands m.breteler{at}erasmusmc.nl

Background: Depression may increase risk for Alzheimer disease (AD), but it is not clear whether this risk is mediated by structural brain changes. We determined whether history of depressive episodes and presence of depressive symptoms were associated with smaller hippocampal and amygdalar volumes and with increased risk for incident AD.

Methods: Within the Rotterdam Scan Study 503 persons, aged 60–90 years at baseline and without dementia, reported their history of depressive episodes. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. Volumetric assessment of the hippocampus and amygdala was performed using three-dimensional MRI. All subjects were followed for an average of 6 years for development of AD, diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke–Alzheimer’s Disease and Related Disorders Association criteria.

Results: A total of 134 subjects (26.6%) reported a history of depression (88 reported an onset <60 years and 46 a late onset). Multiple linear regression analyses did not reveal a significant association with hippocampal or amygdalar volume for any of the depression parameters. During follow-up, 33 persons developed AD. Cox regression analyses showed that subjects with early onset depression had an increased risk for AD (HR 3.76; 95% CI 1.41 to 10.06), independent of hippocampal and amygdalar volume, whereas this risk was 2.34 (95% CI 0.82 to 6.69) in subjects with a late-onset depression. Depressive symptoms at baseline were not associated with increased risk for AD.

Conclusion: History of depression, and particularly an early onset, but not presence of depressive symptoms increased the risk for Alzheimer disease. This risk was not mediated by smaller hippocampal or amygdalar volumes.

Abbreviations: AD = Alzheimer disease; CAMDEX = Cambridge Examination for Mental Disorders of the Elderly; CES-D = Center for Epidemiologic Studies Depression Scale; HASTE = half-Fourier acquisition single-shot turbo spin-echo; HPA = hypothalamic-pituitary-adrenal; ICV = intracranial volume; MMSE = Mini-Mental State Examination.

Supported by The Netherlands Organisation for Scientific Research (NWO) and the Health Research and Development Council (ZonMW).

Disclosure: The authors report no conflicts of interest.

Received June 1, 2007. Accepted in final form August 14, 2007.