Hostname: page-component-6bf8c574d5-vmclg Total loading time: 0 Render date: 2025-02-15T17:24:37.492Z Has data issue: false hasContentIssue false
  • English
  • Français

Clinical and neuropathological correlates of depression in Alzheimer's disease

Published online by Cambridge University Press:  09 July 2009

Hans Förstl ,
Alistair Burns ,
Philip Luthert ,
Nigel Cairns ,
Peter Lantos  and
Raymond Levy
Hans Förstl*
Affiliation:
Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London
Alistair Burns
Affiliation:
Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London
Philip Luthert
Affiliation:
Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London
Nigel Cairns
Affiliation:
Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London
Peter Lantos
Affiliation:
Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London
Raymond Levy
Affiliation:
Section of Old Age Psychiatry and the Department of Neuropathology, Institute of Psychiatry, London
*
1 Address for correspondence: Dr Hans Förstl, Central Institute of Mental Health, PO Box 122–120, I 5, W-6800 Mannheim 1, Germany.
Get access Rights & Permissions [Opens in a new window]

Synopsis

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.

Type
Original Articles
Information
Psychological Medicine , Volume 22 , Issue 4 , November 1992 , pp. 877 - 884
Copyright
Copyright © Cambridge University Press 1992

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Alzheimer, A. (1902). Die Seelenstörungen auf arteriosklerotischer Grundlage. Allgemeine Zeitschrift für Psychiatrie 59, 695–710. Translated by Förstl, H., Howard, R. & Levy, R. (1992). Mental disturbances of arteriosclerotic origin. Neuropsychiatry, Neuropsychology and Behavioral Neurology 5, 1–6.Google Scholar
Alzheimer, A. (1911). Ūber eigenartige Krankheiten des späteren Alters. Zeitschrift für die Gesamte Neurologie und Psychiatrie 4, 356–385. Translated by Förstl, H. & Levy, R. (1991). On certain peculiar diseases of old age. History of Psychiatry 2, 71–101.CrossRefGoogle Scholar
American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders, 3rd ed., revised. American Psychiatric Association: Washington, DC.Google Scholar
Barclay, L. L., Zemcov, A., Blass, J. & Sansone, J. (1985). Survival in Alzheimer's disease and vascular dementias. Neurology 35, 834–840.CrossRefGoogle ScholarPubMed
Bondareff, W., Mountjoy, C. Q., Roth, M., Rossor, M. N., Iversen, L. & Reynolds, G. (1986). Age and histopathological heterogeneity in Alzheimer's disease: evidence for subtypes. Archives of General Psychiatry 44, 412–417.CrossRefGoogle Scholar
Bondareff, W., Mountjoy, C. Q., Roth, M., Rossor, M. N., Iversen, L. L., Reynolds, G. P. & Hauser, D. L. (1987). Neuronal degeneration in locus ceruleus and cortical correlates of Alzheimer disease. Alzheimer Disease and Associated Disorders 1, 256–262.CrossRefGoogle ScholarPubMed
Burns, A., Jacoby, R. & Levy, R. (1990 a). Psychiatric phenomena in Alzheimer's disease. British Journal of Psychiatry 157, 72–76.CrossRefGoogle ScholarPubMed
Burns, A., Luthert, P., Levy, R., Jacoby, R. & Lantos, P. (1990 b). Accuracy of clinical diagnosis of Alzheimer's disease. British Medical Journal 301, 1026.CrossRefGoogle ScholarPubMed
Chan-Palay, V. & Asan, E. (1989 a). Quantitation of catecholamine neurons in the locus coeruleus in human brains of normal young and older adults and in depression. Journal of Comparative Neurology 287, 357–372.CrossRefGoogle Scholar
Chan-Palay, V. & Asan, E. (1989 b). Alterations in catecholamine neurons of the locus coeruleus in senile dementia of the Alzheimer type and in Parkinson's disease with and without dementia and depression. Journal of Comparative Neurology 287, 373–392.CrossRefGoogle ScholarPubMed
Copeland, J. R. M., Kelleher, M. J., Kellett, J. M., Gourlay, A. J., Gurland, B. J., Fleiss, J. L. & Sharpe, L. (1976). A semi-structured clinical interview for the assessment of diagnosis and mental state in the elderly: the Geriatric Mental State Schedule. I. Development and reliability. Psychological Medicine 6, 439–449.CrossRefGoogle Scholar
Eastwood, M. R., Corbin, S. L., Reed, M., Nobbs, H. & Kedward, H. B. (1985). Acquired hearing loss and psychiatric illness: an estimate of prevalence and co-morbidity in a geriatric setting. British Journal of Psychiatry 147, 552–556.CrossRefGoogle Scholar
Folstein, M. F., Folstein, S. E. & McHugh, P. R. (1975). ‘Mini-Mental state’. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189–198.CrossRefGoogle Scholar
Forno, L. S. (1978). The locus caeruleus in Alzheimer's disease. Journal of Neuropathology and Experimental Neurology 37, 614.CrossRefGoogle Scholar
Förstl, H., Almeida, O. P., Owen, A., Burns, A. & Howard, R. (1991). Psychiatric, neurological and medical aspects of misidentification syndromes: a review of 260 cases. Psychological Medicine 21, 905–910.CrossRefGoogle ScholarPubMed
Förstl, H., Burns, A., Levy, R., Cairns, N., Luthert, P. & Lantos, P. (1992 a). Neurological signs in Alzheimer's disease: results of a prospective clinical and neuropathological study. Archives of Neurology (in the press).Google Scholar
Förstl, H., Burns, A., Luthert, P., Cairns, N. & Levy, R. (1992 b). The Lewy-body variant of Alzheimer's disease: clinical and pathological findings. British Journal of Psychiatry (in the press).CrossRefGoogle Scholar
Gellerstedt, N. (1933). Zur Kenntnis der Hirnveränderungen bei der normalen Altersinvolution. Upsala Läkareförenings Förhandlingar 38, 193–408.Google Scholar
Häfner, H. (1986). Psychische Gesundheit im Alter, (Mental Health in Old Age). G. Fischer: Stuttgart.Google Scholar
Hankoff, L. D. & Peress, N. S. (1981). Neuropathology of the brain stem in psychiatric disorders. Biological Psychiatry 16, 945–952.Google Scholar
Ichimaya, Y., Arai, H., Kosaka, K. & Iizuka, R. (1986). Morphological and biochemical changes in the cholinergic and monoaminergic systems in Alzheimer-type dementia. Acta Neuropathologica 70, 112–116.CrossRefGoogle Scholar
Jeste, D. V., Lohr, J. B. & Goodwin, F. K. (1988). Neuroanatomical studies of major affective disorders: a review and suggestions for further research. British Journal of Psychiatry 153, 444–459.CrossRefGoogle ScholarPubMed
Knesevich, J. W., Martin, R. L., Berg, L. & Danziger, W. (1983). Preliminary report on affective symptoms in the early stages of senile dementia of the Alzheimer type. American Journal of Psychiatry 10, 233–235.Google Scholar
Lopez, O. L., Boller, F., Becker, J. T., Miller, M. & Reynolds, C. F. (1990). Alzheimer's disease and depression: neuropsychological impairment and progression of the illness. American Journal of Psychiatry 17, 855–860.Google Scholar
Mackenzie, T. B., Robiner, W. N. & Knopman, D. S. (1989). Differences between patient and family assessments of depression in Alzheimer's disease. American Journal of Psychiatry 16, 1174–1178.Google Scholar
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. & Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services Task Force on Alzheimer's disease. Neurology 34, 939–944.CrossRefGoogle ScholarPubMed
Mann, D. M. A., Yates, P. O. & Marcyniuk, B. (1984). A comparison of changes in the nucleus basalis and locus caeruleus in Alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry 47, 201–203.CrossRefGoogle ScholarPubMed
Marcyniuk, B., Mann, D. M. A. & Yates, P. O. (1986). The topography of cell loss from locus caeruleus in Alzheimer's disease. Journal of the Neurological Sciences 76, 335–345.CrossRefGoogle ScholarPubMed
Maxwell, S. E. & Delaney, H. D. (1990). Designing Experiments and Analyzing Data. Wadsworth: Belmont, Ca.Google Scholar
Mayeux, R., Stern, Y. & Spanton, S. (1983). Heterogeneity in dementia of the Alzheimer type: evidence of subgroups. Neurology 35, 53–61.Google Scholar
Merriam, A. E., Aronson, M. K., Gaston, P., Wey, S.-L. & Katz, I. (1988). The psychiatric symptoms of Alzheimer's disease. Journal of the American Geriatric Society 36, 7–12.CrossRefGoogle ScholarPubMed
Mesulam, M.-M. & Geula, C. (1988). Nucleus basalis and cortical cholinergic innervation in the human brain: observations based on the distribution of acetylcholinesterase and choline acetyltransferase. Journal of Comparative Neurology 275, 216–240.Google Scholar
Norusis, M. J. (1988). SPSS/PC + V2.0. SPSS Inc.: Chicago, IL.Google Scholar
Reding, M., Haycox, J. & Blass, J. (1985). Depression in patients referred to a dementia clinic: a three-year prospective study. Archives of Neurology 2, 894–896.CrossRefGoogle Scholar
Reifler, B. V., Larson, E., Teri, L. & Poulsen, M. (1986). Dementia of the Alzheimer's type and depression. Journal of the American Geriatric Society 3, 855–859.CrossRefGoogle Scholar
Reifter, B. V., Teri, L., Raskind, M., Veith, R., Barnes, R., White, E. & McLean, P. (1989). Double-blind trial of imipramine in Alzheimer's disease patients with and without depression. American Journal of Psychiatry 146, 45–49.Google Scholar
Roth, M., Tym, E., Mountjoy, C., Huppert, F., Hendrie, H., Verma, S. & Goddard, R. (1985). CAMDEX: a standardized instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. British Journal of Psychiatry 149, 698–709.CrossRefGoogle Scholar
Rovner, B. W., Broadhead, J., Spencer, M., Carson, K. & Folstein, M. F. (1989). Depression and Alzheimer's disease. American Journal of Psychiatry 16, 350–353.Google Scholar
Rubin, E. H. & Kinscherf, D. (1989). Psychopathology of very mild dementia of the Alzheimer type. American Journal of Psychiatry 146, 1017–1021.Google Scholar
Rubin, E. H., Kinscherf, D. A., Grant, E. A. & Storandt, M. (1991). The influence of major depression on clinical and psychometric assessment of senile dementia of the Alzheimer type. American Journal of Psychiatry 18, 1164–1171.Google Scholar
Saper, C. B. & Petito, C. K. (1982). Correspondence of melaninpigmented neurons in human brain with A1–A14 catecholamine cell groups. Brain 105, 87–101.CrossRefGoogle ScholarPubMed
Schildkraut, J. J. (1965). The catecholamine hypothesis of affective disorders: a review of supporting evidence. American Journal of Psychiatry 122, 483–497.CrossRefGoogle ScholarPubMed
Sunderland, T., Alterman, I. S., Yount, D., Hill, J. L., Tariot, P. N., Newhouse, P. A., Mueller, E. A., Mellow, A. M. & Cohen, R. M. (1988). A new scale for the assessment of depressed mood in demented patients. American Journal of Psychiatry 145, 955–959.Google ScholarPubMed
Thal, L. J., Grundman, M. & Klauber, M. R. (1988). Dementia: characteristics of a referral population and factors associated with progression. Neurology 38, 1083–1090.Google ScholarPubMed
Tomlinson, B. E., Irving, D. & Blessed, G. (1981). Cell loss in the locus coeruleus in senile dementia of Alzheimer type. Journal of the Neurological Sciences 49, 419–428.CrossRefGoogle ScholarPubMed
Veith, R. C. & Raskind, M. A. (1988). The neurobiology of aging: does it predispose to depression? Neurobiology of Aging 9, 101–117.CrossRefGoogle ScholarPubMed
Vijashankar, N. & Brody, H. (1979). A quantitative study of the pigmented neurons in the nuclei locus coeruleus and subcoeruleus in man as related to aging. Journal of Neuropathology and Experimental Neurology 38, 490–498.CrossRefGoogle Scholar
Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T. and DeJong, M. R. (1981). Alzheimer disease: evidence for a selective loss of cholinergic neurons in the nucleus basalis. Annals of Neurology 10, 122–126.CrossRefGoogle ScholarPubMed
World Health Organization (1978). Mental Disorders Glossary and Guide to their Classification in Accordance with the Ninth Revision of the International Classification of Diseases. World Health Organization: Geneva.Google Scholar
Wragg, R. E. & Jeste, D. V. (1989). Overview of depression and psychosis in Alzheimer's disease. American Journal of Psychiatry 146, 577–587.Google ScholarPubMed
Zubenko, G. S. & Moossy, J. (1988). Major depression in primary dementia: clinical and neuropathologic correlates. Archives of Neurology 45, 1182–1186.CrossRefGoogle ScholarPubMed
Zweig, R. M., Ross, C. A., Hedreen, J. C., Steele, C., Cardillo, J. E., Whitehouse, P. J., Folstein, M. F. & Price, D. L. (1988). The neuropathology of aminergic nuclei in Alzheimer's disease. Annals of Neurology 24, 233–242.CrossRefGoogle ScholarPubMed