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Witte J. G. Hoogendijk, MD, PhD; Iris E. C. Sommer, MD; Chris W. Pool, PhD; Wouter Kamphorst, MD, PhD; Michel A. Hofman, PhD; Piet Eikelenboom, MD, PhD; Dick F. Swaab, MD, PhD

Arch Gen Psychiatry. 1999;56:45-51.

Background  Depression, one of the most frequent psychiatric disturbances in Alzheimer disease (AD), is proposed to have its neurobiological basis in neuron loss in the noradrenergic locus coeruleus, although this is not the case in idiopathic depression.

Methods  We performed image analyzer–assisted morphometry of the locus coeruleus in 6 depressed, 6 transiently depressed, and 6 nondepressed patients with AD and in 8 control subjects, emphasizing longitudinal psychiatric evaluations and matching for the clinical and neuropathological severity of dementia.

Results  The mean (±SD) number of pigmented neurons in the locus coeruleus in controls (11,607±946) was higher than in patients with AD, regardless of being depressed (5165±928; P=.001), transiently depressed (5647±1163; P=.003), or nondepressed (3717±661; P=.001). No significant difference was found in the number of pigmented neurons between patients with AD who were depressed, transiently depressed, and nondepressed. Patients who had depression at the onset of AD had a higher pigmented neuron number than other patients with AD.

Conclusions  We confirmed the loss of pigmented neurons in the locus coeruleus of patients with AD; however, no supplementary loss of pigmented neurons in the locus coeruleus was found in patients with depression and AD. This finding resembles the situation in idiopathic depression, but is in contrast with earlier studies on depression in AD.

From the Netherlands Institute for Brain Research (Drs Hoogendijk, Pool, Hofman, and Swaab); Research Institute Neurosciences, Free University, Faculty of Medicine, Department of Psychiatry, Valerius Clinic (Drs Hoogendijk, Sommer, and Eikelenboom); and the Department of Neuropathology, Institute of Pathology (Dr Kamphorst), Amsterdam, the Netherlands.

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