Skip to main content
PMC home page
Journal of Neurology, Neurosurgery, and Psychiatry logoLink to Journal of Neurology, Neurosurgery, and Psychiatry
. 1993 Dec;56(12):1282–1289. doi: 10.1136/jnnp.56.12.1282

Cholinergic treatment of an amnestic man with a basal forebrain lesion: theoretical implications.

A Chatterjee 1, M K Morris 1, D Bowers 1, D J Williamson 1, L Doty 1, K M Heilman 1
PMCID: PMC1015375  PMID: 8270928

Abstract

Cholinergic deficient states, such as in Alzheimer's disease, are associated with amnesia. Therapeutic trials with cholinergic augmentation in Alzheimer's disease have had only equivocal results, but mechanisms other than cholinergic deficiency may contribute to the memory deficit. Normally the diagonal band of Broca provides much of the hippocampal cholinergic input. To learn if amnesia secondary to cholinergic deficiency can be ameliorated by cholinergic augmentation, we treated an amnestic man who had a lesion located primarily in the right diagonal band of Broca with physostigmine and lecithin. During the initial best-dose-finding phase, he demonstrated an inverted U-shaped curve for immediate recall of word lists, with peak performances at 3.0 and 3.5 mg of physostigmine. Single photon emission tomography showed decreased blood flow in the medial temporal region ipsilateral to the lesion at baseline, with a reversal of the asymmetry on 3.5 mg of physostigmine. A follow-up double-blind, placebo-controlled study on 3.5 mg of physostigmine, however, failed to demonstrate that cholinergic treatment improved memory.

Full text

PDF
1282

Images in this article

1283Image
on p.1283
1284Image
on p.1284
1285Image
on p.1285
1288Image
on p.1288

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aigner T. G., Mitchell S. J., Aggleton J. P., DeLong M. R., Struble R. G., Price D. L., Wenk G. L., Mishkin M. Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert. Psychopharmacology (Berl) 1987;92(3):292–300. doi: 10.1007/BF00210833. [DOI] [PubMed] [Google Scholar]
  2. Albert M. L. A simple test of visual neglect. Neurology. 1973 Jun;23(6):658–664. doi: 10.1212/wnl.23.6.658. [DOI] [PubMed] [Google Scholar]
  3. Albert M. S., Butters N., Levin J. Temporal gradients in the retrograde amnesia of patients with alcoholic Korsakoff's disease. Arch Neurol. 1979 Apr;36(4):211–216. doi: 10.1001/archneur.1979.00500400065010. [DOI] [PubMed] [Google Scholar]
  4. Crow T. J., Grove-White I. G. An analysis of the learning deficit following hyoscine administration to man. Br J Pharmacol. 1973 Oct;49(2):322–327. doi: 10.1111/j.1476-5381.1973.tb08379.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Damasio A. R., Graff-Radford N. R., Eslinger P. J., Damasio H., Kassell N. Amnesia following basal forebrain lesions. Arch Neurol. 1985 Mar;42(3):263–271. doi: 10.1001/archneur.1985.04060030081013. [DOI] [PubMed] [Google Scholar]
  6. Damasio A. R. Time-locked multiregional retroactivation: a systems-level proposal for the neural substrates of recall and recognition. Cognition. 1989 Nov;33(1-2):25–62. doi: 10.1016/0010-0277(89)90005-x. [DOI] [PubMed] [Google Scholar]
  7. Dudchenko P., Sarter M. GABAergic control of basal forebrain cholinergic neurons and memory. Behav Brain Res. 1991 Jan 31;42(1):33–41. doi: 10.1016/s0166-4328(05)80037-3. [DOI] [PubMed] [Google Scholar]
  8. Dunnett S. Cholinergic grafts, memory and ageing. Trends Neurosci. 1991 Aug;14(8):371–376. doi: 10.1016/0166-2236(91)90166-r. [DOI] [PubMed] [Google Scholar]
  9. Frith C. D., Richardson J. T., Samuel M., Crow T. J., McKenna P. J. The effects of intravenous diazepam and hyoscine upon human memory. Q J Exp Psychol A. 1984 Feb;36(1):133–144. doi: 10.1080/14640748408401507. [DOI] [PubMed] [Google Scholar]
  10. Geaney D. P., Soper N., Shepstone B. J., Cowen P. J. Effect of central cholinergic stimulation on regional cerebral blood flow in Alzheimer disease. Lancet. 1990 Jun 23;335(8704):1484–1487. doi: 10.1016/0140-6736(90)93028-n. [DOI] [PubMed] [Google Scholar]
  11. Harrell L. E., Jope R. S., Falgout J., Callaway R., Avery C., Spiers M., Leli D., Morere D., Halsey J. H., Jr Biological and neuropsychological characterization of physostigmine responders and nonresponders in Alzheimer's disease. J Am Geriatr Soc. 1990 Feb;38(2):113–122. doi: 10.1111/j.1532-5415.1990.tb03471.x. [DOI] [PubMed] [Google Scholar]
  12. Hunter R., Wyper D. J., Patterson J., Hansen M. T., Goodwin G. M. Cerebral pharmacodynamics of physostigmine in Alzheimer's disease investigated using single-photon computerised tomography. Br J Psychiatry. 1991 Mar;158:351–357. doi: 10.1192/bjp.158.3.351. [DOI] [PubMed] [Google Scholar]
  13. Hyman B. T., Van Hoesen G. W., Damasio A. R., Barnes C. L. Alzheimer's disease: cell-specific pathology isolates the hippocampal formation. Science. 1984 Sep 14;225(4667):1168–1170. doi: 10.1126/science.6474172. [DOI] [PubMed] [Google Scholar]
  14. Kopelman M. D., Corn T. H. Cholinergic 'blockade' as a model for cholinergic depletion. A comparison of the memory deficits with those of Alzheimer-type dementia and the alcoholic Korsakoff syndrome. Brain. 1988 Oct;111(Pt 5):1079–1110. doi: 10.1093/brain/111.5.1079. [DOI] [PubMed] [Google Scholar]
  15. Morris M. K., Bowers D., Chatterjee A., Heilman K. M. Amnesia following a discrete basal forebrain lesion. Brain. 1992 Dec;115(Pt 6):1827–1847. doi: 10.1093/brain/115.6.1827. [DOI] [PubMed] [Google Scholar]
  16. PETERSON L. R., PETERSON M. J. Short-term retention of individual verbal items. J Exp Psychol. 1959 Sep;58:193–198. doi: 10.1037/h0049234. [DOI] [PubMed] [Google Scholar]
  18. Paivio A., Yuille J. C., Madigan S. A. Concreteness, imagery, and meaningfulness values for 925 nouns. J Exp Psychol. 1968 Jan;76(1 Suppl):1–25. doi: 10.1037/h0025327. [DOI] [PubMed] [Google Scholar]
  19. Perry E. K., Tomlinson B. E., Blessed G., Bergmann K., Gibson P. H., Perry R. H. Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia. Br Med J. 1978 Nov 25;2(6150):1457–1459. doi: 10.1136/bmj.2.6150.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Richardson J. T. Performance in free recall following rupture and repair of intracranial aneurysm. Brain Cogn. 1989 Mar;9(2):210–226. doi: 10.1016/0278-2626(89)90031-6. [DOI] [PubMed] [Google Scholar]
  21. Stern Y., Sano M., Mayeux R. Effects of oral physostigmine in Alzheimer's disease. Ann Neurol. 1987 Sep;22(3):306–310. doi: 10.1002/ana.410220305. [DOI] [PubMed] [Google Scholar]
  22. Thal L. J., Fuld P. A., Masur D. M., Sharpless N. S. Oral physostigmine and lecithin improve memory in Alzheimer disease. Ann Neurol. 1983 May;13(5):491–496. doi: 10.1002/ana.410130504. [DOI] [PubMed] [Google Scholar]
  23. Wettstein A. No effect from double-blind trial of physostigmine and lecithin in Alzheimer disease. Ann Neurol. 1983 Feb;13(2):210–212. doi: 10.1002/ana.410130220. [DOI] [PubMed] [Google Scholar]
  24. Whitehouse P. J., Price D. L., Clark A. W., Coyle J. T., DeLong M. R. Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol. 1981 Aug;10(2):122–126. doi: 10.1002/ana.410100203. [DOI] [PubMed] [Google Scholar]
  25. Whitehouse P. J., Unnerstall J. R. Neurochemistry of dementia. Eur Neurol. 1988;28 (Suppl 1):36–41. [PubMed] [Google Scholar]
  26. Zola-Morgan S., Squire L. R., Amaral D. G. Human amnesia and the medial temporal region: enduring memory impairment following a bilateral lesion limited to field CA1 of the hippocampus. J Neurosci. 1986 Oct;6(10):2950–2967. doi: 10.1523/JNEUROSCI.06-10-02950.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurology, Neurosurgery, and Psychiatry are provided here courtesy of BMJ Publishing Group

RESOURCES