Psychological Medicine

Original Articles

Clinical and neuropathological correlates of depression in Alzheimer's disease

Hans Förstla1 c1, Alistair Burnsa1, Philip Lutherta1, Nigel Cairnsa1, Peter Lantosa1 and Raymond Levya1

a1 Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London


Depressive symptoms have been reported in patients with mild to moderate Alzheimer's disease (AD). Recent evidence suggests that a noradrenergic deficit originating from neuronal degeneration in brainstem nuclei may represent an organic correlate of these disturbances. We examined the neuropathological changes in the locus coeruleus (LC), substantia nigra (SN), basal nucleus of Meynert and cortex of 52 patients (12 male, 40 female, mean age 83·2 ± 6·4 years) with pathologically verified AD. Fourteen patients (1 male, 13 female) showed signs of depression. The majority of these patients suffered from severe physical disability or sensory impairment and developed persistent delusions, but had less cognitive impairment. Neuronal counts in the LC were significantly lower than in the 38 patients without depression (36·9 ± 14 ·0; 51·4 ± 28·0 neuromelaninpigmented cells per section per nucleus; F = 3·4, df = 1, 50, P = 0·04). Neuron counts were higher in the basal nucleus of Meynert in depressed AD patients and there were no differences of the neuron numbers in the SN. Depression (main effect; F = 4·5, P = 0·04) contributed significantly to the variance of neuronal counts in the LC, even when covarying for gender, age of onset, cognitive impairment and cortical Alzheimer pathology. The observed disproportionate loss of noradrenergic and cholinergic neurons in the LC and basal nucleus of Meynert may represent an important organic substrate of depression in AD.


c1 Address for correspondence: Dr Hans Förstl, Central Institute of Mental Health, PO Box 122–120, I 5, W-6800 Mannheim 1, Germany.