Tuesday, April 08, 2008

Depression History May Foretell Later Alzheimer's Disease

By Judith Groch
ROTTERDAM, The Netherlands, April 7 -- Individuals with a history of depression requiring medical advice were more than twice as likely to develop Alzheimer's disease as those without past depression, a study found.
Furthermore, those with depressive episodes before age 60 had nearly four times the risk for Alzheimer's, Monique Breteler, M.D., Ph.D., of Erasmus University here, and colleagues reported in the April 8 issue of Neurology.
It is not clear whether the depression-Alzheimer's link is mediated by structural brain changes, the researchers wrote. However, in this study there was no difference in the size of the hippocampal or amygdalar structures in people with a depression history and those without depression.
The study included 486 individuals, ages 60 to 90, without dementia at baseline (1995 to 1996), who reported their history of depressive episodes. Individuals came from the prospective Rotterdam Scan Study, which investigated chronic diseases among elderly participants.
Depression was defined as episodes requiring the attention of a general practitioner, psychologist, or psychiatrist.
Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale. Volumetric assessment of the hippocampus and amygdala was done with three-dimensional MRI.
All individuals were followed for an average of six years for development of Alzheimer's disease, diagnosed according to criteria from the National Institute of Neurological and Communicative Disorders and Stroke--Alzheimer's Disease and Related Disorders Association. Screening was done three times through 2003.
A total of 130 individuals (26.7%) had a history of depression, of those 84 (64.6%) reported onset before age 60 (50% women) and 46 (35.4%) onset after age 60 (63% women). At baseline, 35 individuals scored 16 or higher on the depression scale.
During six-year follow-up, 44 persons developed dementia, of whom 33 were diagnosed with Alzheimer's.
Cox regression analysis showed that persons with early onset depression had an increased risk for Alzheimer's (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) for late-onset depression.
Depressive symptoms at baseline (35 individuals) were not associated with structural brain changes or an increased risk for Alzheimer's, the investigators reported.
For each point increase on the depression scale at baseline, the Alzheimer's hazard ratio was 0.99 (95% CI 0.95 to 1.04).
Multiple linear regression analyses found no significant association with hippocampal or amygdalar volume for any of the depression parameters.
The adjusted difference for mean total hippocampal volume for those without a history of depression and those with a depression history was -0.05 (95% CI -0.21 to 0.10).
Similarly, no difference was observed for total amygdalar volume, -0.003, (95% CI -0.12 to 0.13).
It has been hypothesized that depression increases the risk for Alzheimer's through hyperactivity of the hypothalamic-pituitary-adrenal axis, the researchers wrote.
Studies have suggested that prolonged exposure to glucocorticoids with repeated depressive episodes might lead to hippocampal atrophy and subsequently development of Alzheimer's, they noted.
The findings of this study contrast with some clinical studies among patients with major depression or posttraumatic stress disorder that observed structural volume changes on MRI. Although an absence of a relation has also been observed in other studies, the researchers said.
It is possible, they said, that there were too few cases of severe depression to find a significant relation. On the other hand, they said, the risk estimates were fairly similar for all-cause dementia as well, and adjustment for vascular MRI parameters did not alter the estimates.
One possibility, they said, is that the effect of depression is not through the hippocampus or the amygdala but through other brain structures.
Another explanation, they suggested, is that early-onset depression and Alzheimer's are not causally related, but that another unknown factor leads to an increased risk of both depression and Alzheimer's.
In addition to the lack of cases with severe depression, other study limitations included the need to rely on self-reports for depressive episodes.
Also the lack of follow-up measures of brain structural volumes made it impossible to determine the extent to which smaller volumes represented volume loss or pre-existing smaller volumes.
Future studies should determine whether early onset depression is a true risk factor for Alzheimer's disease or whether a third factor causes both, Dr. Breteler and colleagues concluded.
The study was supported by The Netherlands Organization for Scientific Research and the Health Research and Development Council. The authors declared no conflicts of interest.
Primary source: NeurologySource reference:Geerlings MI, et al "History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease" Neurology 2008; 70: 1258-1264.

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