Showing papers by "Iris E. C. Sommer published in 1999"

Increased activity of surviving locus ceruleus neurons in Alzheimer's disease

Abstract: In Alzheimer's disease (AD) there is neuronal loss in the locus ceruleus (LC), and the noradrenergic system may be even more affected in depressed AD patients. However, this neuronal loss may go together with an increase in activity of the remaining noradrenergic neurons. We prospectively evaluated 16 AD patients (6 depressed, 5 transiently depressed, and 5 nondepressed) and 10 controls. We determined norepinephrine and its metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in various brain areas, and compared these data with previously established neuron numbers in the LC in the same patients. We could not confirm earlier studies reporting lower norepinephrine concentrations in depressed than in nondepressed dementia patients. The mean norepinephrine concentrations in AD patients were significantly lower than those in control patients, whereas the mean concentrations of MHPG were not different. Moreover, we found significant inverse relationships between the number of remaining pigmented LC neurons and the MHPG/norepinephrine ratio in the frontal cortex and LC. These data are the first to provide direct evidence for the hypothesis that remaining LC neurons are activated to compensate for decreased cerebral norepinephrine levels in AD, by demonstrating that the MHPG/norepinephrine ratio is significantly higher in AD, indicating increased metabolism.

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

Abstract: 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.