Abstract
Monoamine neurotransmitter systems, along with cholinergic systems, are known to play important roles in cognition, and are disrupted in at least some patients with dementia of the Alzheimer type (DAT). This suggests that monoamine-enhancing drugs might ameliorate cognitive symptoms in certain patients with DAT. l-Deprenyl is a monoamine oxidase (MAO) inhibitor which may selectively inhibit MAO-B at low doses, while at high doses it nonselectively inhibits MAO-A as well as MAO-B. We studied its effects on several types of cognitive function in 17 patients with DAT. Two doses of l-deprenyl (10 mg/day and 40 mg/day) and placebo were compared in a double-blind, serial treatment design. Episodic learning and memory, knowledge memory, attention, recognition, and performance on a continuous performance task were assessed at baseline and under these drug and placebo conditions. Statistically significant improvement was noted in performance on an episodic memory and learning task requiring complex information processing and sustained conscious effort during treatment with l-deprenyl 10 mg/day. Knowledge memory, intrusions, and other cognitive functions relevant to DAT were not altered by l-deprenyl at either dose.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Adolfsson R, Gottfries CG, Roos BE, Winblad B (1979) Changes in brain catecholamines in patients with dementia of Alzheimer type. Br J Psychiatry 135:216–223
Adolfsson R, Gottfries CG, Oreland L, Wiberg A, Winblad B (1980) Increased activity of brain and platelet monoamine oxidase in dementia of Alzheimer type. Life Sci 17:1029–1034
Anzelark GM, Crow TJ, Greenway AP (1973) Impaired learning and decreased cortical norepinephrine after bilateral locus coeruleus lesions. Science 181:682–684
Arai H, Kosaka K, Iizuka R (1984) Changes of biogenic amines and their metabolites in postmortem brains from patients with Alzheimer-type dementia. J Neurochem 43(2):388–393
Birkmayer W, Riederer P, Youdim MBH (1982) (-) Deprenyl in the treatment of Parkinson's disease. Clin Neuropharmacol 5(2):195–230
Bondareff W, Mountjoy CQ, Roth M (1982) Loss of neurons of origin of the adrenergic projection to cerebral cortex (nucleus locus coeruleus) in senile dementia. Neurology 32:164–168
Brinkman S, Gershon S (1983) Measurement of cholinergic drug effect on memory in Alzheimer's disease. Neurobiol Aging 4:139–145
Buschke H (1973) Selective reminding for the analysis of memory and learning. J Verb Learn Verb Behav 12:543–550
Clark ANG, Mankikar GD (1979) d-Amphetamine in elderly patients refractory to rehabilitation procedures. J Am Geriatr Soc 27:174–177
Cohen RM, Weingartner H, Smallberg SA, Pickar D, Murphy DL (1982) Effort and cognition in depression. Arch Gen Psychiatry 32:593–597
Cohen RM, Cohen MR, Weingartner H, Pickar D, Murphy DL (1983) Naloxone affects task performance in normal subjects. Psychiatry Res 8:127–136
Cohen RM, Sunderland T, Aulakh CS (1984) Antidepressants in states of cognitive dysfunction. Drug Dev Res 4:517–532
Crook T, Ferris S, Sathananthan G, Raskin A, Gershon S (1977) The effect of methylphenidate on test performance in the cognitively impaired aged. Psychopharmacology 52:251–257
Cross AJ, Crow TJ, Perry EK, Perry RH, Blessed G, Tomlinson BE (1981) Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease. Br Med J 282:93–94
Elliott PB (1964) Tables of d1. In: Swets JA (ed) Signal detection and recognition by human observers. Wiley, New York, pp 651–684
Ellsworth JD, Glover V, Reynolds GP, Sandler M, Lees AJ, Phuapradit P, Shaw KM, Stein GM, Kumar P (1978) Deprenyl administration in man: A selective monoamine oxidase inhibitor without the “cheese” effect. Psychopharmacology 57:33–38
Francis PT, Palmer AM, Sims NR, Bowen DM, Davison AN, Esiri MM, Neary D, Snowdon JS, Wilcock GK (1985) Neurochemical studies of early-onset Alzheimer's disease: Possible influence on treatment. N Engl J Med 313(1):7–11
Fuld PA, Katzman R, Davies P, Terry RD (1982) Intrusions as a sign of Alzheimer dementia: Chemical and pathological verification. Ann Neurol 11:155–159
Glass RM, Uhlenhuth EH, Hartel FW, Matuzas W, Fischman MW (1981) Cognitive dysfunction and imipramine in outpatient depressives. Arch Gen Psychiatry 38:1048–1051
Gorelick DA, Bozewicz TR, Bridger WH (1975) The role of catecholamines in animal learning and memory. In: Friedhoff AJ (ed) Catecholamines and behavior, vol 2. Plenum, New York, pp 1–30
Gottfries CG (1985) Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. Psychopharmacology 86:245–252
Hamilton M (1967) Development of a rating scale for primary depressive illness. Br J Soc Psychol 6:278–296
Hasher L, Zacks RJ (1979) Automatic and effortful processes in memory. J Exp Psychol [Gen] 108:386–388
Henry GM, Weingartner H, Murphy DL (1973) The influence of affective states and psychoactive drugs on verbal learning and memory. Am J Psychiatry 130:966–971
Hopkins NF, Johnston D (1984) Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus. Science 226:350–352
Karoum F, Chuang L-W, Eisler T, Calne DB, Liebowitz MR, Quitkin MR, Klein DF, Wyatt RJ (1982) Metabolism of (-) deprenyl to amphetamine and methamphetamine. Neurology 32:503–509
Kety SF (1970) The biogenic amines in the central nervous system: Their possible roles in arousal, emotion, and learning. In: Schmitt FO (ed) The neurosciences: second study program. Rockefeller Press, New York, pp 324–336
Knoll J (1976) Analysis of the pharmacological effects of selective monoamine oxidase inhibitors. CIBA Foundation Symposium 39, Monoamine oxidase and its inhibition. Elsevier/North Holland, Excerpta Medical, pp 135–161
Knoll J, Ecseri Z, Kelmen K, Nievel J, Knoll B (1965) Phenylisopropylmethylpropinylamine (E-250), a new spectrum psychic energizer. Arch Int Pharmacodyn Ther 155(1):154–164
Mann DA, Lincoln J, Yates PO, Stamp JE, Toper S (1980) Changes in the monoamine containing neurons of the human CNS in senile dementia. Br J Psychiatry 136:533–541
Mann JJ, Frances A, Kaplan R, Kocsis J, Peselow ED, Gershon S (1982) The relative efficacy of l-deprenyl, a selective monoamine oxidase type B inhibitor, in endogenous and nonendogenous depression. J Clin Psychopharmacol 2:54–57
McGaugh JL (1983) Hormonal influences on memory. Annu Rev Psychol 34:297–323
McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM (1984) Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group. Neurology 34:939–944
Mendis N, Pare CMB, Sandler M, Glover V, Stern GM (1981) Is the failure of (-) deprenyl, a selective MAO B inhibitor, to alleviate depression related to freedom from cheese effect? Psychopharmacology 73:87–90
Mendlewicz J, Youdim MBH (1983) l-Deprenil, a selective monoamine oxidase type B inhibitor, in the treatment of depression: A double-blind evaluation. Br J Psychiatry 142:508–511
Moss MB, Albert MS, Butters N, Payne M (1986) Differential patterns of memory loss among patients with Alzheimer's disease, Huntington's disease, and alcoholic Korsakoff's syndrome. Arch Neurol 43:239–246
Murphy DL, Henry GM, Weingartner H (1972) Catecholamines and memory: Enhanced verbal learning during l-dopa administration. Psychopharmacologia 27:319–326
Palermo DS, Jenkins JJ (1964) Word association norms: Grade school through college. Univ Minnesota Press, Minneapolis
Quitkin FM, Liebowitz MR, Stewart JW, McGrath PJ, Harrison W, Rabkin JG, Markowitz J, Davies SO (1984) l-Deprenyl in atypical depressives. Arch Gen Psychiatry 41:777–781
Reisberg B, Ferris SH, DeLeon MJ, Crook T (1982) The global deterioration scale for assessment of primary degenerative dementia. Am J Psychiatry 139(9):1136–1139
Reynolds GP, Elsworth JD, Blau K, Sandler M, Lees AJ, Stern GM (1978) Deprenyl is metabolized to amphetamine and methamphetamine in man. Br J Clin Pharmacol 6:542–543
Reus VI, Silberman E, Post RM, et al. (1979) d-Amphetamine: Effects on memory in a depressed population. Biol Psychiatry 14:345–356
Robinson DS, Davis JM, Nies A, Colburn RW, Davis JN, Bourne HR, Bunney WE, Shaw DM, Coppen AJ (1972) Ageing, monoamines, and monoamine oxidase levels. Lancet I:290–291
Rossor MN, Iversen LL, Reynolds GP, Mountjoy CO, Roth M (1984) Neurochemical characteristics of early and late onset types of Alzheimer's disease. Br Med J 288:961–964
Rosvold HE, Mirsky AF, Sarason I (1956) A continuous performance test of brain damage. J Consult Clin Psychol 20:343–350
Roy-Byrne PP, Weingartner H, Bierer L, Thompson K, Post RM (1986) Effortful and automatic cognitive processes in depression. Arch Gen Psychiatry 43:265–267
Squire LR, Davis HP (1981) The pharmacology of memory: A neurobiological perspective. Annu Rev Pharmacol Toxicol 21:323–356
Sternberg DE, Jarvik ME (1976) Memory functions in depression: Improvement with antidepressant medication. Arch Gen Psychiatry 33:219–224
Sunderland T, Tariot PN, Cohen RM, Weingartner H, Mueller EA, Murphy DL (1987) Anticholinergic sensitivity in Alzheimer patients and age-matched controls. Arch Gen Psychiatry (in press)
Tariot PN, Sunderland T, Weingartner H, Murphy DL, Cohen MR, Cohen RM (1986) Naloxone and Alzheimer's disease. Arch Gen Psychiatry 43:727–732
Tariot PN, Weingartner H (1986) A psychobiologic analysis of cognitive failures: Structure and mechanisms. Arch Gen Psychiatry 43:1183–1188
Tariot PN, Cohen RM, Sunderland T, Newhouse PA, Yount D, Mellow AM, Weingartner H, Mueller EA, Murphy DL (1987) l-deprenyl in Alzheimer's disease: preliminary evidence for behavioral change with MAO-B inhibition. Arch Gen Psychiatry (in press)
Weingartner H, Cohen RM, Murphy DL, Martello J, Gerdt C (1981) Cognitive processes in depression. Arch Gen Psychiatry 38:42–47
Weingartner H, Grafman J, Boutelle W, Kaye W, Martin PR (1983) Forms of memory failure. Science 221:380–382
Wise RA (1978) Catecholamine theories of reward: A critical review. Brain Res 152:215–247
Woods SW, Tesar GE, Murray GB, Cassem NH (1986) Psychostimulant treatment of depressive disorders secondary to medical illness. J Clin Psychiatry 47:12–15
Yates CM, Simpson J, Gordon A, Maloney AFJ, Allison Y, Ritchie IM, Urquhart A (1983) Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down's syndrome. Brain Res 280:119–126
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tariot, P.N., Sunderland, T., Weingartner, H. et al. Cognitive effects of l-deprenyl in Alzheimer's disease. Psychopharmacology 91, 489–495 (1987). https://doi.org/10.1007/BF00216016
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00216016