Cited by 5,545Cholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment ResearchNeuroscience and Neuropharmacology Research

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The Cholinergic Hypothesis of Geriatric Memory Dysfunction

Bartus, Raymond T., Dean, Reginald L., Beer, Bernard, Lippa, Arnold S.·1982·Science

DOI 10.1126/science.7046051

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Abstract

Biochemical, electrophysiological, and pharmacological evidence supporting a role for cholinergic dysfunction in age-related memory disturbances is critically reviewed. An attempt has been made to identify pseudoissues, resolve certain controversies, and clarify misconceptions that have occurred in the literature. Significant cholinergic dysfunctions occur in the aged and demented central nervous system, relationships between these changes and loss of memory exist, similar memory deficits can be artificially induced by blocking cholinergic mechanisms in young subjects, and under certain tightly controlled conditions reliable memory improvements in aged subjects can be achieved after cholinergic stimulation. Conventional attempts to reduce memory impairments in clinical trials hav not been therapeutically successful, however. Possible explanations for these disappointments are given and directions for future laboratory and clinical studies are suggested.

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Authors: Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S.
Affiliations: NYU Langone Health (US)
Department of CNS Research, Lederle Laboratories of American Cyanamid Co., Pearl River, New York 10965.
ORCID: Dean, Reginald L.
Lippa, Arnold S.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1982-07-30
Volume: 217
Issue: 4558
Pages: 408-414
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.7046051
OpenAlex: W1994067502
Cited by: 5,545
References: 158
Citations by year: 2026: 66 · 2025: 98 · 2024: 90 · 2023: 107 · 2022: 130 · 2021: 142 · 2020: 123 · 2019: 119 · 2018: 130 · 2017: 116 · 2016: 122 · 2015: 111 · 2014: 139 · 2013: 145 · 2012: 132
FWCI: 11.90
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords: cholinergic hypothesis, age-related memory impairment, cholinergic dysfunction, dementia, cholinergic stimulation, cholinergic blockade
MeSH terms: Acetylcholine, Adult, Aged, Aging, Alzheimer Disease, Animals, Brain Chemistry, Choline, Choline O-Acetyltransferase, Cognition, Forecasting, Humans, Memory, Memory Disorders, Models, Neurological, Parasympathetic Nervous System, Parasympathomimetics, Phosphatidylcholines, Receptors, Muscarinic, Mice, Rats

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The Cholinergic Hypothesis of Geriatric Memory Dysfunction

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