Lewy bodies in the amygdala increase risk for major depression in subjects with Alzheimer disease
Lopez OL, Becker JT, Sweet RA, Martin-Sanchez FJ, Hamilton RL;
Commented by , 27 Sep 2006
Aim of the study
To determine the relationship between major depression and the presence of Lewy bodies (LBs) in patients with Alzheimer’s disease (AD).
Method
Chart review of 267 pathologically diagnosed AD cases with MMSE scores >9, to find evidence of major depression, active or in remission at the time of initial clinical visit at the AD Research Center at the University of Pittsburgh. Histological examination of brain using alpha-synuclein immunohistochemistry to find evidence of LBs with emphasis on location, taking into account the Consensus Guidelines for the pathologic diagnosis for Dementia with Lewy Bodies (DLB).
Results
LBs were identified in 142 (53%) of patients; 26 cases had LBs only in the amygdala. Major depression was present in 11 (9%) of AD alone cases, 25 (18%) of AD with LBs in the amygdala with or without LBs in the cortical areas. There was an association between all amygdala LBs cases 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).
Professor Gauthier's comments
The authors conclude that LBs in the amygdala increase the risk of major depression in AD. This information is important since the pathological substrate for the common neuropsychiatric symptoms of AD is lacking.
Depression is common in early stages of AD and DLB, although not usually major in severity. It tends to improve spontaneously as patients lose insight into their condition, and appears to be responsive to selective serotonin re-uptake inhibitors such as citalopram and sertraline. The authors highlight the fact that the deposition of LBs in the amygdala could well be an early stage phenomenon since depression occurs early in AD (and sometimes before dementia is diagnosable).
They hypothesize that LBs may alter the functional connectivity of this structure. The authors already established that symptoms of depression preceding or concomitant with dementia convey an increased risk of death, but not when depression develops later in the course of AD (ref. 1). This is also true of psychotic symptoms (ref. 2). The overall message is that depressive symptoms preceding or concomitant with a diagnosis of dementia convey a poor prognostic, require treatment, and may have a specific anatomical substrate.
Readers should be aware that the Consensus Guidelines for the pathologic diagnosis for DLB used in this study (ref. 3) have been updated earlier this year (ref. 4).
References
1. Lopez OL, Wisniewski SR, Becker JT, Boller F, DeKosky ST. Psychiatric medication and abnormal behavior as predictors of progression in probable Alzheimer disease Archives of Neurology 1999; 56 (10); 1266-1272 (Free full text article)
2. Stern Y, Mayeux R, Sano M, Hauser WA, Bush T. Predictors of disease course in patients with probable Alzheimer's disease Neurology 1987; 37 (10); 1649-1653
3. McKeith IG, Galasko D, Kosaka K, Perry EK, Dickson DW, Hansen LA, et al. Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB): report of the consortium on DLB international workshop Neurology 1996; 47 (5); 1113-1124
4. McKeith IG, Dickson DW, Lowe J, Emre M, O'Brien JT, Feldman H, et al. Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium Neurology 2005; 65 (12); 1863-1872 [Epub 2005 Oct 19]