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Lewy bodies in the amygdala increase risk for major depression in subjects with Alzheimer disease

From Alzheimer's Disease Research Center (O.L.L., J.T.B., R.A.S., F.J.M.-S., R.L.H.), Departments of Neurology (O.L.L., J.T.B.), Psychiatry (O.L.L., J.T.B., R.A.S.), Psychology (J.T.B.), and Pathology (R.L.H.), University of Pittsburgh School of Medicine, PA.

Address correspondence and reprint requests to Dr. Oscar L. Lopez, 3501 Forbes Avenue, Suite 830, Oxford Building, Pittsburgh, PA 15213; e-mail: lopezol{at}upmc.edu.

Objective: To determine the relationship between major depression and the presence of Lewy bodies (LBs) in patients with Alzheimer disease (AD).

Methods: The authors examined the presence of major depression in 267 pathologically diagnosed AD cases with Mini-Mental State Examination (MMSE) scores >9. LBs were identified in 142 (53%) patients using alpha-synuclein immunohistochemistry. Subjects were classified according to the Consensus Guidelines for the Clinical and Pathologic Diagnosis of Dementia with LB: 1 to 2 (n = 21), 3 to 6 (n = 26), and 7 to 10 (n = 69). Twenty-six patients had LB only in the amygdala. All cases with LB scores 7 to 10 (or cortical) had amygdala LBs. The association between LBs and major depression was examined with logistic regression analyses, controlled for age at study entry, education level, MMSE scores, antidepressant use, follow-up time, and the presence of cerebrovascular disease.

Results: Major depression was present in 11 (9%) AD alone cases, and in 25 (18%) of the AD + LBs cases; amygdala: 8 (31%), scores 1 to 2: 1 (5%), scores 3 to 6: 3 (11.5%), and scores 7 to 10: 13 (14%). Major depression was associated with LBs, in general (relative risk [RR] = 3.06, 95% CI: 1.25 to 7.46), with amygdala only LBs (RR = 8.56 (95% CI: 1.83 to 40.3), and with LB scores 7 to 10 (RR = 3.83, 95% CI: 1.33 to 11.0). There was an association between all amygdala LBs cases (amygdala only LBs + LB scores 7 to 10) and major depression (RR = 4.77, 95% CI: 1.78 to 12.7), but no association was noted between LBs and depression in the absence of amygdala LBs (RR = 0.96, 95% CI: 0.46 to 1.06).

Conclusion: Lewy bodies (LBs) in the amygdala and in cortical areas increase the risk for major depression in Alzheimer disease. What is common in these two groups is the presence of LBs in the amygdala. That is, all of the cases with cortical LBs also had LBs in the amygdala, making this region the critical area for the development of depression.

Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the August 22 issue to find the title link for this article.

Supported by grants AG03705 and AG05133 from the National Institute on Aging, and MH52247 from the National Institute of Mental Health. J.T.B. is a recipient of the Research Scientist Development Award (Level II) (K02-MH01077).

Disclosure: The authors report no conflicts of interest.

Received January 5, 2005.

Accepted in final form April 27, 2006.