Abstract
BACKGROUND—The cholinergic nucleus basalis (Ch4) is an exclusive site of neurofibrillary degeneration in alcoholic patients with Wernicke's encephalopathy. Aim—To test the hypothesis that the loss of Ch4 neurons contributes to the memory disorder, Korsakoff's psychosis, commonly seen in Wernicke's encephalopathy. METHODS—Magnocellular basal forebrain neurons were quantified in alcoholic patients with Wernicke's encephalopathy, both with and without Korsakoff's psychosis, and neurologically asymptomatic alcoholic and non-alcoholic controls. Because amnesic and non-amnesic patients with Wernicke's encephalopathy share common periventricular lesions, both thiamine deficient groups as well as alcoholic patients with no neurological complications were included to determine the lesion specific to memory impairment. RESULTS—Ch4 cell number did not differ significantly between alcoholic and non-alcoholic controls and there was no correlation between cell number and lifetime alcohol intake. However, Ch4 cell number in all groups was significantly correlated with the volume of its major projection target, the cerebral cortex. Ch4 cell number in the non-amnesic Wernicke's encephalopathy group was significantly below controls (24%), with cell number in patients with Korsakoff's psychosis 21% below controls. There was considerable overlap in cell number between groups. On discriminant analysis, there was significantly greater cell loss in three non-amnesic patients with Wernicke's encephalopathy than in some patients with Korsakoff's psychosis. The non-amnesic patient with the greatest cell loss was impaired on attentional tasks. CONCLUSION—Whereas neurons in the nucleus basalis are at risk in thiamine deficient alcoholic patients, cell loss is minor and does not account for the profound memory disorder.
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- Arendt T., Bigl V., Arendt A., Tennstedt A. Loss of neurons in the nucleus basalis of Meynert in Alzheimer's disease, paralysis agitans and Korsakoff's Disease. Acta Neuropathol. 1983;61(2):101–108. doi: 10.1007/BF00697388. [DOI] [PubMed] [Google Scholar]
- Arendt T., Brückner M. K., Bigl V., Marcova L. Dendritic reorganisation in the basal forebrain under degenerative conditions and its defects in Alzheimer's disease. II. Ageing, Korsakoff's disease, Parkinson's disease, and Alzheimer's disease. J Comp Neurol. 1995 Jan 9;351(2):189–222. doi: 10.1002/cne.903510203. [DOI] [PubMed] [Google Scholar]
- Blokland A. Acetylcholine: a neurotransmitter for learning and memory? Brain Res Brain Res Rev. 1995 Nov;21(3):285–300. doi: 10.1016/0165-0173(95)00016-x. [DOI] [PubMed] [Google Scholar]
- Butters N. Alcoholic Korsakoff's syndrome: some unresolved issues concerning etiology, neuropathology, and cognitive deficits. J Clin Exp Neuropsychol. 1985 Apr;7(2):181–210. doi: 10.1080/01688638508401252. [DOI] [PubMed] [Google Scholar]
- Caine D., Halliday G. M., Kril J. J., Harper C. G. Operational criteria for the classification of chronic alcoholics: identification of Wernicke's encephalopathy. J Neurol Neurosurg Psychiatry. 1997 Jan;62(1):51–60. doi: 10.1136/jnnp.62.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cullen K. M., Halliday G. M., Cartwright H., Kril J. J. Improved selectivity and sensitivity in the visualization of neurofibrillary tangles, plaques and neuropil threads. Neurodegeneration. 1996 Jun;5(2):177–187. doi: 10.1006/neur.1996.0025. [DOI] [PubMed] [Google Scholar]
- Cullen K. M., Halliday G. M., Double K. L., Brooks W. S., Creasey H., Broe G. A. Cell loss in the nucleus basalis is related to regional cortical atrophy in Alzheimer's disease. Neuroscience. 1997 Jun;78(3):641–652. doi: 10.1016/s0306-4522(96)00569-6. [DOI] [PubMed] [Google Scholar]
- Cullen K. M., Halliday G. M. Neurofibrillary tangles in chronic alcoholics. Neuropathol Appl Neurobiol. 1995 Aug;21(4):312–318. doi: 10.1111/j.1365-2990.1995.tb01065.x. [DOI] [PubMed] [Google Scholar]
- Double K. L., Halliday G. M., Kril J. J., Harasty J. A., Cullen K., Brooks W. S., Creasey H., Broe G. A. Topography of brain atrophy during normal aging and Alzheimer's disease. Neurobiol Aging. 1996 Jul-Aug;17(4):513–521. doi: 10.1016/0197-4580(96)00005-x. [DOI] [PubMed] [Google Scholar]
- Freund G. Chronic central nervous system toxicity of alcohol. Annu Rev Pharmacol. 1973;13:217–227. doi: 10.1146/annurev.pa.13.040173.001245. [DOI] [PubMed] [Google Scholar]
- Geula C., Schatz C. R., Mesulam M. M. Differential localization of NADPH-diaphorase and calbindin-D28k within the cholinergic neurons of the basal forebrain, striatum and brainstem in the rat, monkey, baboon and human. Neuroscience. 1993 May;54(2):461–476. doi: 10.1016/0306-4522(93)90266-i. [DOI] [PubMed] [Google Scholar]
- Halliday G. M., Cullen K., Cairns M. J. Quantitation and three-dimensional reconstruction of Ch4 nucleus in the human basal forebrain. Synapse. 1993 Sep;15(1):1–16. doi: 10.1002/syn.890150102. [DOI] [PubMed] [Google Scholar]
- Harper C. G., Kril J. J. Neuropathology of alcoholism. Alcohol Alcohol. 1990;25(2-3):207–216. doi: 10.1093/oxfordjournals.alcalc.a044994. [DOI] [PubMed] [Google Scholar]
- Jacobson R. R., Lishman W. A. Selective memory loss and global intellectual deficits in alcoholic Korsakoff's syndrome. Psychol Med. 1987 Aug;17(3):649–655. doi: 10.1017/s0033291700025885. [DOI] [PubMed] [Google Scholar]
- Kato T., Hirano A., Katagiri T., Sasaki H., Yamada S. Neurofibrillary tangle formation in the nucleus basalis of Meynert ipsilateral to a massive cerebral infarct. Ann Neurol. 1988 Jun;23(6):620–623. doi: 10.1002/ana.410230617. [DOI] [PubMed] [Google Scholar]
- Kril J. J., Halliday G. M., Svoboda M. D., Cartwright H. The cerebral cortex is damaged in chronic alcoholics. Neuroscience. 1997 Aug;79(4):983–998. doi: 10.1016/s0306-4522(97)00083-3. [DOI] [PubMed] [Google Scholar]
- Linville D. G., Williams S., Arneric S. P. Basal forebrain control of cortical cerebral blood flow is independent of local cortical neurons. Brain Res. 1993 Sep 17;622(1-2):26–34. doi: 10.1016/0006-8993(93)90797-q. [DOI] [PubMed] [Google Scholar]
- Lishman W. A. Alcoholic dementia: a hypothesis. Lancet. 1986 May 24;1(8491):1184–1186. doi: 10.1016/s0140-6736(86)91162-1. [DOI] [PubMed] [Google Scholar]
- Melis F., Stancampiano R., Imperato A., Carta G., Fadda F. Chronic ethanol consumption in rats: correlation between memory performance and hippocampal acetylcholine release in vivo. Neuroscience. 1996 Sep;74(1):155–159. doi: 10.1016/0306-4522(96)00109-1. [DOI] [PubMed] [Google Scholar]
- Mesulam M. M., Geula C. Nucleus basalis (Ch4) and cortical cholinergic innervation in the human brain: observations based on the distribution of acetylcholinesterase and choline acetyltransferase. J Comp Neurol. 1988 Sep 8;275(2):216–240. doi: 10.1002/cne.902750205. [DOI] [PubMed] [Google Scholar]
- Nevo I., Hamon M. Neurotransmitter and neuromodulatory mechanisms involved in alcohol abuse and alcoholism. Neurochem Int. 1995 Apr;26(4):305–342. doi: 10.1016/0197-0186(94)00139-l. [DOI] [PubMed] [Google Scholar]
- Okeda R., Taki K., Ikari R., Funata N. Vascular changes in acute Wernicke's encephalopathy. Acta Neuropathol. 1995;89(5):420–424. doi: 10.1007/BF00307646. [DOI] [PubMed] [Google Scholar]
- Salmon D. P., Butters N. The etiology and neuropathology of alcoholic Korsakoff's syndrome. Some evidence for the role of the basal forebrain. Recent Dev Alcohol. 1987;5:27–58. [PubMed] [Google Scholar]
- Torvik A. Topographic distribution and severity of brain lesions in Wernicke's encephalopathy. Clin Neuropathol. 1987 Jan-Feb;6(1):25–29. [PubMed] [Google Scholar]
- Victor M. Alcoholic dementia. Can J Neurol Sci. 1994 May;21(2):88–99. doi: 10.1017/s031716710004899x. [DOI] [PubMed] [Google Scholar]
- Voytko M. L., Olton D. S., Richardson R. T., Gorman L. K., Tobin J. R., Price D. L. Basal forebrain lesions in monkeys disrupt attention but not learning and memory. J Neurosci. 1994 Jan;14(1):167–186. doi: 10.1523/JNEUROSCI.14-01-00167.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Walker L. C., Koliatsos V. E., Kitt C. A., Richardson R. T., Rökaeus A., Price D. L. Peptidergic neurons in the basal forebrain magnocellular complex of the rhesus monkey. J Comp Neurol. 1989 Feb 8;280(2):272–282. doi: 10.1002/cne.902800208. [DOI] [PMC free article] [PubMed] [Google Scholar]
