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Human Memory and the Cholinergic System: A Relationship to Aging?

Human Memory and the Cholinergic System: A Relationship to Aging? Abstract The relationship of the cholinergic system of the brain to memory and cognitive functions was studied in human subjects by the use of scopolamine, methscopolamine bromide, and physostigmine. A battery of tests evaluated immediate memory span, memory storage (acquisition), and retrieval, as well as nonmemory cognitive ability. Subjects receiving scopolamine showed impairment of memory storage and possibly retrieval despite normal immediate memory span; nonmemory cognitive functions were also impaired. Neither methscopolamine (a peripherally acting scopolamine analogue) nor physostigmine (a centrally acting anticholinesterase agent) produced any significant changes in memory or other cognitive functions. Comparisons of the memory and cognitive deficits induced by scopolamine with the performance of aged subjects revealed a marked similarity of pattern. The possible theoretical explanations for the behavioral similarity seen with central cholinergic blockade and normal aging are discussed. References 1. Scoville WB, Milner B: Loss of recent memory after bilateral hippocampal lesions . J Neurol Neurosurg Psychiatry 20:11-21, 1957.Crossref 2. Penfield W, Milner B: Memory deficit produced by bilateral lesions in the hippocampal zone . Arch Neurol Psychiatry 79:475-497, 1958.Crossref 3. Drachman DA, Ommaya AK: Memory and the hippocampal complex . Arch Neurol 10:411-425, 1964.Crossref 4. Drachman DA, Arbit J: Memory and the hippocampal complex: II . Is memory a multiple process? Arch Neurol 15:52-61, 1966. 5. Milner B: Brain mechanisms suggested by studies of temporal lobes , in Darley FL (ed): Brain Mechanisms Underlying Speech and Language . New York, Grune & Stratton Inc, 1967, pp 122-145. 6. Victor M, Adams RD, Collins GH: Wernicke-Korsakoff Syndrome , publication 7. Contemporary Neurological series, Philadelphia, FA Davis, 1971, pp 206. 7. Warrington EK: Neurological disorders of memory . Br Med Bull 27:243-247, 1971. 8. Barbizet J: Human Memory and Its Pathology . San Francisco, WH Freeman & Co, 1970, pp 198. 9. John ER: Switchboard versus statistical theories of learning and memory . Science 177:850-864, 1972.Crossref 10. Pribram KH, Broadbent DE (eds): Biology of Memory . New York, Academic Press, 1970, pp 323. 11. Ojemann RG: Correlations between specific human brain lesions and memory changes . Neurosciences Res Prog Bull 4( (suppl) ):1-70, 1966. 12. Meissner WW: Hippocampal functions in learning , J Psychiatr Res 4:235-304, 1966.Crossref 13. Eccles JC: Possible ways in which synaptic mechanisms participate in learning, remembering and forgetting , in Kimble DP (ed): The Anatomy of Memory . Palo Alto, Calif, Science & Behavior Books, 1965, pp 12-87. 14. Meldrum BS: Electrical signals in the brain and the cellular mechanisms of learning , in Richter D (ed): Aspects of Learning and Memory . New York, Basic Books, 1966, pp 100-120. 15. Whitty CWM, Lisham WA: Amnesia in cerebral disease , in Whitty CWM, Zangwill OL (eds): Amnesia . New York, Appleton-Century-Crofts, 1966, pp 36-76. 16. Murphy DL: L-DOPA, behavioral activation and psychopathology . Res Publ Assoc Res Nerv Ment Dis 50:472-492, 1972. 17. Innes IR, Nickerson N: Drugs inhibiting the action of acetylcholine on structures innovated by postganglionic parasympathetic nerves (antimuscarinic or atropinic drugs , in Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan Co, 1970, pp 524-548. 18. Koelle GB: Anticholinesterase agents , in Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan Co, 1970, pp 442-465. 19. Drachman DA, Leavitt J: Memory impairment in the aged: Storage versus retrieval deficit . J Exp Psychol 93:302-308, 1972.Crossref 20. Safer DJ, Allen RP: The central effects of scopolamine in man . Biol Psychiatry 3:347-355, 1971. 21. Duvoisin R: Cholinergic-anticholinergic antagonism in parkinsonism . Arch Neurol 17:124-136, 1967.Crossref 22. Pfeiffer CC, Jenney H: The inhibition of the conditioned response and the counteraction of schizophrenia by muscarinic stimulation of the brain . Ann NY Acad Med 66:753-764, 1957.Crossref 23. Wechsler D: Manual for the Wechsler Adult Intelligence Scale . New York, Psychological Corporation, 1955, p 40. 24. Drachman DA, Zaks MS: The memory cliff beyond span in immediate recall . Psychol Rep 21:105-112, 1967.Crossref 25. Drachman DA, Hughes JR: Memory and the hippocampal complexes: III. Aging and temporal EEG abnormalities . Neurology 21:1-14, 1971.Crossref 26. Carlton P, Markiewicz B: Behavioral effects of atropine and scopolamine , in Furchigott E (ed): Pharmacological and Biophysical Agents and Behavior . New York, Academic Press, 1971, pp 345-373. 27. Grossman S: Cholinergic synapses in the limbic system and behavioral inhibition . Res Publ Assoc Nerv Ment Dis 50:315-326, 1972. 28. Wickelgren WA: Sparing of short-term memory in an amnesic patient: Implications for strength theory of memory . Neuropsychologia 6:235-244, 1968.Crossref 29. Iverson S, Weiskrantz L: Temporal lobe lesions and memory in the monkey . Nature 201:740-742, 1964.Crossref 30. Atkinson RC, Shiffrin RM: The control of short-term memory . Sci Am 225:82-90, 1971.Crossref 31. Atkinson RC, Shiffrin RM: Human memory: A proposed system and its control processes , in Spence KW, Spence JT (eds): The Psychology of Learning and Motivation: Advances in Research and Theory . New York, Academic Press, 1968, vol 2, pp 89-195. 32. Weiskrantz L: Comparison of amnesic states in monkey and man , in Jarrard LE (ed): Cognitive Processes of Nonhuman Primates . New York, Academic Press, 1971, pp 25-46. 33. Kintsch W: Learning, Memory and Conceptual Processes . New York, John Wiley & Sons Inc, 1970, p 498. 34. Hrbek J, et al: On the acute effects of scopolamine and physostigmine on verbal association . Activitas Nervosa Superior 12:273-276, 1970. 35. Hrbek J, et al: Effect of physostigmine on the inhibitory action of scopolamine in man . Activitas Nervosa Superior 13:199-200, 1971. 36. Ostfeld AM, Aruguete A: Central nervous system effects of hyoscine in man . J Pharmacol Exp Ther 137:133-139, 1962. 37. Domino EF, Corssen G: Central and peripheral effects of muscarinic cholinergic blocking agents in man . Anesthesiology 28:568-574, 1967.Crossref 38. Dundee JW, Pandit SK: Anterograde amnesic effects of pethidine, myoscine and diazepam in adults . Br J Pharmacol 44:140-144, 1972.Crossref 39. Crow TJ, Grove-White IG: Differential effects of atropine and hyoscine on human learning capacity . Br J Pharmacol 43:464, 1971. 40. Berger BD, Stein L: An analysis of the learning deficits produced by scopolamine . Psychopharmacologia 14:271-283, 1969.Crossref 41. Chiappetta L, Jarvik ME: Comparison of learning impairment and activity depression produced by two classes of cholinergic blocking agents . Arch Int Pharmacodyn 179:161-166, 1969. 42. Renfro CT, Freeman PE, Rosen AJ: The concurrent effects of scopolamine on spontaneous motor activity and the acquisition of an active avoidance response . Neuropharmacology 11:337-346, 1972.Crossref 43. Meyers B: Some effects of scopolamine on a passive avoidance response in rats . Psychopharmacologia 8:111-119, 1965.Crossref 44. Deutsch JA: The cholinergic synapse and the site of memory . Science 174:788-794, 1971.Crossref 45. Deutsch JA, Rocklin K: Anticholinesterase amnesia as a function of massed or spaced retest . J Comp Physiol Psychol 81:64-68, 1972.Crossref 46. Hamburg MD: Retrograde amnesia produced in intraperitoneal injection of physostigmine . Science 156:973-974, 1967.Crossref 47. Bohdanecky Z, Jarvik ME: The effect of D-amphetamine and physostigmine upon acquisition and retrieval in a single-trial learning task . Arch Int Pharmacodyn 170:58-65, 1967. 48. Shute CCD, Lewis PR: The ascending cholinergic reticular system: Neocortical, olfactory and subcortical projections . Brain 90:497-520, 1967.Crossref 49. Lewis PR, Shute CCD: The cholinergic limbic system: Projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest . Brain 90:521-540, 1967.Crossref 50. Krnjevic K: Central cholinergic pathways . Fed Proc 28:113-120, 1969. 51. Leaton RN: The limbic system and its pharmacological aspects , in Rech RH, Moore KE (eds): An Introduction to Psychopharmacology . New York: Raven Press, 1971, pp 137-174. 52. Karczmar AG: Is the central cholinergic nervous system overexploited? Fed Proc 28:147-159, 1969. 53. Kooi KA, Guvener AM, Tupper CJ: Electroencephalographic patterns of the temporal region in normal adults . Neurology 14:1029-1035, 1964.Crossref 54. Tomlinson BE, Blessed G, Roth M: Observations on the brains of non-demented old people . J Neurol Sci 7:331-356, 1968.Crossref 55. Lashley KS: Brain Mechanisms and Intelligence . Chicago, University of Chicago Press, 1929, p 186. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Neurology American Medical Association

Human Memory and the Cholinergic System: A Relationship to Aging?

Archives of Neurology , Volume 30 (2) – Feb 1, 1974

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American Medical Association
Copyright
Copyright © 1974 American Medical Association. All Rights Reserved.
ISSN
0003-9942
eISSN
1538-3687
DOI
10.1001/archneur.1974.00490320001001
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Abstract

Abstract The relationship of the cholinergic system of the brain to memory and cognitive functions was studied in human subjects by the use of scopolamine, methscopolamine bromide, and physostigmine. A battery of tests evaluated immediate memory span, memory storage (acquisition), and retrieval, as well as nonmemory cognitive ability. Subjects receiving scopolamine showed impairment of memory storage and possibly retrieval despite normal immediate memory span; nonmemory cognitive functions were also impaired. Neither methscopolamine (a peripherally acting scopolamine analogue) nor physostigmine (a centrally acting anticholinesterase agent) produced any significant changes in memory or other cognitive functions. Comparisons of the memory and cognitive deficits induced by scopolamine with the performance of aged subjects revealed a marked similarity of pattern. The possible theoretical explanations for the behavioral similarity seen with central cholinergic blockade and normal aging are discussed. References 1. Scoville WB, Milner B: Loss of recent memory after bilateral hippocampal lesions . J Neurol Neurosurg Psychiatry 20:11-21, 1957.Crossref 2. Penfield W, Milner B: Memory deficit produced by bilateral lesions in the hippocampal zone . Arch Neurol Psychiatry 79:475-497, 1958.Crossref 3. Drachman DA, Ommaya AK: Memory and the hippocampal complex . Arch Neurol 10:411-425, 1964.Crossref 4. Drachman DA, Arbit J: Memory and the hippocampal complex: II . Is memory a multiple process? Arch Neurol 15:52-61, 1966. 5. Milner B: Brain mechanisms suggested by studies of temporal lobes , in Darley FL (ed): Brain Mechanisms Underlying Speech and Language . New York, Grune & Stratton Inc, 1967, pp 122-145. 6. Victor M, Adams RD, Collins GH: Wernicke-Korsakoff Syndrome , publication 7. Contemporary Neurological series, Philadelphia, FA Davis, 1971, pp 206. 7. Warrington EK: Neurological disorders of memory . Br Med Bull 27:243-247, 1971. 8. Barbizet J: Human Memory and Its Pathology . San Francisco, WH Freeman & Co, 1970, pp 198. 9. John ER: Switchboard versus statistical theories of learning and memory . Science 177:850-864, 1972.Crossref 10. Pribram KH, Broadbent DE (eds): Biology of Memory . New York, Academic Press, 1970, pp 323. 11. Ojemann RG: Correlations between specific human brain lesions and memory changes . Neurosciences Res Prog Bull 4( (suppl) ):1-70, 1966. 12. Meissner WW: Hippocampal functions in learning , J Psychiatr Res 4:235-304, 1966.Crossref 13. Eccles JC: Possible ways in which synaptic mechanisms participate in learning, remembering and forgetting , in Kimble DP (ed): The Anatomy of Memory . Palo Alto, Calif, Science & Behavior Books, 1965, pp 12-87. 14. Meldrum BS: Electrical signals in the brain and the cellular mechanisms of learning , in Richter D (ed): Aspects of Learning and Memory . New York, Basic Books, 1966, pp 100-120. 15. Whitty CWM, Lisham WA: Amnesia in cerebral disease , in Whitty CWM, Zangwill OL (eds): Amnesia . New York, Appleton-Century-Crofts, 1966, pp 36-76. 16. Murphy DL: L-DOPA, behavioral activation and psychopathology . Res Publ Assoc Res Nerv Ment Dis 50:472-492, 1972. 17. Innes IR, Nickerson N: Drugs inhibiting the action of acetylcholine on structures innovated by postganglionic parasympathetic nerves (antimuscarinic or atropinic drugs , in Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan Co, 1970, pp 524-548. 18. Koelle GB: Anticholinesterase agents , in Goodman LS, Gilman A (eds): The Pharmacological Basis of Therapeutics , ed 4. New York, Macmillan Co, 1970, pp 442-465. 19. Drachman DA, Leavitt J: Memory impairment in the aged: Storage versus retrieval deficit . J Exp Psychol 93:302-308, 1972.Crossref 20. Safer DJ, Allen RP: The central effects of scopolamine in man . Biol Psychiatry 3:347-355, 1971. 21. Duvoisin R: Cholinergic-anticholinergic antagonism in parkinsonism . Arch Neurol 17:124-136, 1967.Crossref 22. Pfeiffer CC, Jenney H: The inhibition of the conditioned response and the counteraction of schizophrenia by muscarinic stimulation of the brain . Ann NY Acad Med 66:753-764, 1957.Crossref 23. Wechsler D: Manual for the Wechsler Adult Intelligence Scale . New York, Psychological Corporation, 1955, p 40. 24. Drachman DA, Zaks MS: The memory cliff beyond span in immediate recall . Psychol Rep 21:105-112, 1967.Crossref 25. Drachman DA, Hughes JR: Memory and the hippocampal complexes: III. Aging and temporal EEG abnormalities . Neurology 21:1-14, 1971.Crossref 26. Carlton P, Markiewicz B: Behavioral effects of atropine and scopolamine , in Furchigott E (ed): Pharmacological and Biophysical Agents and Behavior . New York, Academic Press, 1971, pp 345-373. 27. Grossman S: Cholinergic synapses in the limbic system and behavioral inhibition . Res Publ Assoc Nerv Ment Dis 50:315-326, 1972. 28. Wickelgren WA: Sparing of short-term memory in an amnesic patient: Implications for strength theory of memory . Neuropsychologia 6:235-244, 1968.Crossref 29. Iverson S, Weiskrantz L: Temporal lobe lesions and memory in the monkey . Nature 201:740-742, 1964.Crossref 30. Atkinson RC, Shiffrin RM: The control of short-term memory . Sci Am 225:82-90, 1971.Crossref 31. Atkinson RC, Shiffrin RM: Human memory: A proposed system and its control processes , in Spence KW, Spence JT (eds): The Psychology of Learning and Motivation: Advances in Research and Theory . New York, Academic Press, 1968, vol 2, pp 89-195. 32. Weiskrantz L: Comparison of amnesic states in monkey and man , in Jarrard LE (ed): Cognitive Processes of Nonhuman Primates . New York, Academic Press, 1971, pp 25-46. 33. Kintsch W: Learning, Memory and Conceptual Processes . New York, John Wiley & Sons Inc, 1970, p 498. 34. Hrbek J, et al: On the acute effects of scopolamine and physostigmine on verbal association . Activitas Nervosa Superior 12:273-276, 1970. 35. Hrbek J, et al: Effect of physostigmine on the inhibitory action of scopolamine in man . Activitas Nervosa Superior 13:199-200, 1971. 36. Ostfeld AM, Aruguete A: Central nervous system effects of hyoscine in man . J Pharmacol Exp Ther 137:133-139, 1962. 37. Domino EF, Corssen G: Central and peripheral effects of muscarinic cholinergic blocking agents in man . Anesthesiology 28:568-574, 1967.Crossref 38. Dundee JW, Pandit SK: Anterograde amnesic effects of pethidine, myoscine and diazepam in adults . Br J Pharmacol 44:140-144, 1972.Crossref 39. Crow TJ, Grove-White IG: Differential effects of atropine and hyoscine on human learning capacity . Br J Pharmacol 43:464, 1971. 40. Berger BD, Stein L: An analysis of the learning deficits produced by scopolamine . Psychopharmacologia 14:271-283, 1969.Crossref 41. Chiappetta L, Jarvik ME: Comparison of learning impairment and activity depression produced by two classes of cholinergic blocking agents . Arch Int Pharmacodyn 179:161-166, 1969. 42. Renfro CT, Freeman PE, Rosen AJ: The concurrent effects of scopolamine on spontaneous motor activity and the acquisition of an active avoidance response . Neuropharmacology 11:337-346, 1972.Crossref 43. Meyers B: Some effects of scopolamine on a passive avoidance response in rats . Psychopharmacologia 8:111-119, 1965.Crossref 44. Deutsch JA: The cholinergic synapse and the site of memory . Science 174:788-794, 1971.Crossref 45. Deutsch JA, Rocklin K: Anticholinesterase amnesia as a function of massed or spaced retest . J Comp Physiol Psychol 81:64-68, 1972.Crossref 46. Hamburg MD: Retrograde amnesia produced in intraperitoneal injection of physostigmine . Science 156:973-974, 1967.Crossref 47. Bohdanecky Z, Jarvik ME: The effect of D-amphetamine and physostigmine upon acquisition and retrieval in a single-trial learning task . Arch Int Pharmacodyn 170:58-65, 1967. 48. Shute CCD, Lewis PR: The ascending cholinergic reticular system: Neocortical, olfactory and subcortical projections . Brain 90:497-520, 1967.Crossref 49. Lewis PR, Shute CCD: The cholinergic limbic system: Projections to hippocampal formation, medial cortex, nuclei of the ascending cholinergic reticular system, and the subfornical organ and supra-optic crest . Brain 90:521-540, 1967.Crossref 50. Krnjevic K: Central cholinergic pathways . Fed Proc 28:113-120, 1969. 51. Leaton RN: The limbic system and its pharmacological aspects , in Rech RH, Moore KE (eds): An Introduction to Psychopharmacology . New York: Raven Press, 1971, pp 137-174. 52. Karczmar AG: Is the central cholinergic nervous system overexploited? Fed Proc 28:147-159, 1969. 53. Kooi KA, Guvener AM, Tupper CJ: Electroencephalographic patterns of the temporal region in normal adults . Neurology 14:1029-1035, 1964.Crossref 54. Tomlinson BE, Blessed G, Roth M: Observations on the brains of non-demented old people . J Neurol Sci 7:331-356, 1968.Crossref 55. Lashley KS: Brain Mechanisms and Intelligence . Chicago, University of Chicago Press, 1929, p 186.

Journal

Archives of NeurologyAmerican Medical Association

Published: Feb 1, 1974

References