Abstract
Senile dementia of Alzheimer and Alzheimer type (AD/SDAT) is characterized by extensive neuropathological and neurochemical changes including loss of neurons, particularly in specific areas, the presence of amyloid plaques and neurofibrillary tangles, and the hypofunction of many neurotransmitter systems (Katzman, 1986). Among the different neurotransmitter systems affected by this degenerative disease, the hypofunction of the cholinergic system has been the object of much interest for several reasons. The major transmitter change in the brain of patients affected by senile dementia is a 40 to 90% decrease in choline acetyltransferase activity (ChAT) in the hippocampus and neocortex and this decrease can be related to the number of senile plaques in the cerebral cortex (Perry et al., 1978) and the severity of cognitive impairment (Palmer et al., 1987). The cortical and hippocampal ChAT decrease results from the degenerations of cholinergic neurons located in the basal forebrain nuclei. These neuropathological findings are the main foundation of the cholinergic hypothesis of geriatric memory dysfunction (Bartus et al., 1982). The hypothesis represents the rationale for administering cholinomimetic agents to AD/SDAT patients with the purpose of restoring the central cholinergic hypofunction.
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References
Bartus RT, Dean RL, Bee B and Lippa AS (1982): The cholinergic hypothesis of geriatric memory dysfunction. Science 217:408–416.
Becker RE and Giacobini E (1988): Issues in the study and development of cholinomimetic therapy. In: Current Research in Alzheimer Therapy, Giacobini E and Becker R, eds. New York: Taylor and Francis, pp. 1–11.
Casamenti F, Mantovani P, Amaducci L and Pepeu G (1979): Effect of phosphatidylserine on acetylcholine output from the cerebral cortex of the rat. J Neurochem 32:529–533.
Casamenti F, Scali C and Pepeu G (1991): Phosphatidylserine reverses the age-dependent decrease in cortical acetylcholine release: a microdialysis study. Eur J Pharmacol 194:11–16.
Giacobini E and Becker R (1988): Current Research in Alzheimer Therapy, Giacobini E and Becker R, eds. New York: Taylor and Francis.
Harbaugh RE (1987): Intracerebroventricular cholinergic drug administration in Alzheimer’s disease: preliminary results of a double blind study. In: Alzheimer’s Disease: Advances in Basic Research and Therapies. Wurtman RJ, Corkin SH and Growdon JH, eds. Proceeding of the fourth meeting of the international study group on the pharmacology of memory disorders associated with aging. Zurich. Center for Brain Sciences and Metabolism Charitable Trust, Cambridge, MA, pp. 315–323.
Katzman R (1986): Alzheimer’s disease. AT Engl J Med 314:964–973.
Mouradian MM, Mohr E, Williams MA and Chase TN (1987): No response to high-dose muscarinic agonist therapy in Alzheimer’s disease. Neurol 38:606–608.
Palmer AM, Francis PT, Benton JS, Sims NR, Mannn DMA and Neary D et al. (1987): Presynaptic serotoninergic dysfunction in patients with Alzheimer’s Disease. J Neurochem 48:8–15.
Pedata F, Giovannelli G, Spignoli G and Pepeu G (1985): Phosphatidylserine increases acetylcholine release from cortical slices in aged rats. Neurobiol Aging 6:337–339.
Pepeu G and Spignoli G (1989): Nootropic drugs and brain cholinergic mechanisms. Prog Neuropsychopharmacol & Biol Psych 13:S77–S88.
Pepeu G and Marconcini Pepeu I (1991): Phosphatidylserine and preclinical experimental models: biochemical results. In: Diagnosis and Treatment of Adult-Onset Cognitive Disorders (AOCD). Crook T, ed. Madison: Mark Powley Inc. (In Press).
Pepeu G, Gori G and Bartolini L (1980): Pharmacologic and therapeutic perspectives on dementia: an experimental approach. In: Aging of the brain and dementia. Amaducci L, Davison AN and Antuono P, eds. New York: Raven Press, pp 271–274.
Pepeu G, Spignoli G, Giovannini MG and Magnani M (1989): The relationship between behavioral effects of cognition-enhancing drugs and brain acetylcholine. Pharmacopsychiat 22:116–119(Suppl).
Pepeu G, Marconcini Pepeu I and Casamenti F (1990): The validity of animal models in the search for drugs for the aging brain. Drug Des Del 7:1–10.
Perry EK, Tomlinson BE, Blessed G, Bergman K, Gibson PH and Perry RH (1978): Correlation of cholinergic abnormality with senile plaques and mental test scores in senile dementia. Brit Med J 2:1457–1459.
Schindler U, Rush DK and Fielding S (1984): Nootropic drugs: animal models for studying effects on cognition. Drug Dev Res 4:567–576.
SMID Group (1988): Phosphatidylserine in the treatment of Alzheimer’s disease: results of a multicenter study. Psychopharmacol Bull 24:130–142.
Spignoli G and Pepeu G (1986): Oxiracetam prevents electroshock-induced decrease in brain acetylcholine and amnesia. Eur J Pharmacol 126:253–257.
Spignoli G and Pepeu G (1987): Interaction between oxiracetam, aniracetam and scopolamine on behavior and brain acetylcholine. Pharmacol Biochem Behav 27:491–495.
Vannucchi G and Pepeu G (1987): Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aged rats. Neurobiol Aging 8:403–407.
Vannucchi G, Casamenti F and Pepeu G (1990): Decrease in acetylcholine release from cortical slices in aged rats investigations into its reversal by phosphatidylserine. J Neurochem 55:819–825.
Villardita C, Parmi J, Grioli M, Quattropani M, Lomeo C and Scapagnini U (1987): Clinical and neuropsychological study with oxiracetam versus placebo in patients with mild to moderate dementia. J Neural Transm 24 (Suppl):293–298.
Zanotti A, Valzelli G and Toffano G (1986): Reversal of scopolamine-induced amnesia by phosphatidylserine in rats. Psychopharmacol 90:274–275.
Zanotti A, Valzelli L and Toffano G (1989): Chronic phosphatidylserine treatment improves spatial memory and passive avoidance in aged rats. Psychopharmacol 99:316–321.
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Pepeu, G., Giovannini, M.G., Casamenti, F., Scali, C., Rodino, P. (1991). Activation of the Brain Cholinergic System by Noncholinomimetic Agents. In: Becker, R., Giacobini, E. (eds) Cholinergic Basis for Alzheimer Therapy. Advances in Alzheimer Disease Therapy. Birkhäuser, Boston, MA. https://doi.org/10.1007/978-1-4899-6738-1_23
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DOI: https://doi.org/10.1007/978-1-4899-6738-1_23
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