Lack of association between depression and loss of neurons in the locus coeruleus in Alzheimer disease

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 (5105 +/- 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 nith 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.