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

The DOI matches its Crossref record; 158 of the 158 references it cites were found in a registry or an index.

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

Open this paper in CoChat — free account

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.

Integrity signals

Registry

Crossref · 10.1126/science.7046051

Cites

158 of 158 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Alzheimer's Disease and Senile Dementia: Loss of Neurons in the Basal Forebrain
Whitehouse, P., Price, D., Struble, R., Clark, A., Coyle, J., & DeLong, M. R. (1982) · Science · doi:10.1126/science.7058341 · Cited by 3,627
SELECTIVE LOSS OF CENTRAL CHOLINERGIC NEURONS IN ALZHEIMER'S DISEASE
DAVIES, P. (1976) · The Lancet · doi:10.1016/s0140-6736(76)91936-x · Cited by 3,565
Correlation of cholinergic abnormalities with senile plaques and mental test scores in senile dementia.
Perry, E., Tomlinson, B. E., Blessed, G., Bergmann, K., Gibson, P., & Perry, R. H. (1978) · British medical journal · doi:10.1136/bmj.2.6150.1457 · Cited by 2,043
Alzheimer disease: Evidence for selective loss of cholinergic neurons in the nucleus basalis
Whitehouse, P. J., Price, D. L., Clark, A. W., Coyle, J. T., & DeLong, M. R. (1981) · Annals of Neurology · doi:10.1002/ana.410100203 · Cited by 1,736
Cognitive Deficit Caused by Regional Depletion of Dopamine in Prefrontal Cortex of Rhesus Monkey
Brozoski, T. J., Brown, R. M., Rosvold, H. E., & Goldman, P. S. (1979) · Science · doi:10.1126/science.112679 · Cited by 1,500
Human Memory and the Cholinergic System
Drachman, D. A. (1974) · Archives of Neurology · doi:10.1001/archneur.1974.00490320001001 · Cited by 1,398
NEUROTRANSMITTER-RELATED ENZYMES AND INDICES OF HYPOXIA IN SENILE DEMENTIA AND OTHER ABIOTROPHIES
Bowen, D. M., Smith, C. B., White, P., & DAVISON, A. N. (1976) · Brain · doi:10.1093/brain/99.3.459 · Cited by 1,313
APRIORITY
Asher, R. (1961) · The Lancet · doi:10.1016/s0140-6736(61)91217-x · Cited by 1,293
THE ASCENDING CHOLINERGIC RETICULAR SYSTEM: NEOCORTICAL, OLFACTORY AND SUBCORTICAL PROJECTIONS
Shute, C. C. D., & Lewis, P. R. (1967) · Brain · doi:10.1093/brain/90.3.497 · Cited by 1,120
NECROPSY EVIDENCE OF CENTRAL CHOLINERGIC DEFICITS IN SENILE DEMENTIA
Perry, E., Perry, R., Blessed, G., & Tomlinson, B. E. (1977) · The Lancet · doi:10.1016/s0140-6736(77)91780-9 · Cited by 1,070

Flagged first, then by citations

Show all 158 references

Research works printed but not linked: 36

BARBEAU, A, LECITHIN IN NEUROLOGIC DISORDERS, NEW ENGLAND JOURNAL OF MEDICINE 299: 200 (1978).
BARTUS, R.T., AGING 10: 85 (1979).
BONDAREFF, W, LANCET 1: 784 (1981).
BOWEN, D.M., TREATMENT OF ALZHEIMERS-DISEASE - A CAUTIONARY NOTE, NEW ENGLAND JOURNAL OF MEDICINE 305: 1016 (1981).
BOYD, W.D., CLINICAL EFFECTS OF CHOLINE IN ALZHEIMER SENILE DEMENTIA, LANCET 2: 711 (1977).
CAIRD, W.K., J GERONTOL 21: 195 (1966).
DAVIES, P, BRAIN RES 138: 385 (1978).
DAVIS, K.L., LIFE SCI 22: 2699 (1978).
DAVIS, K.L., CHOLINE FOR TARDIVE-DYSKINESIA, NEW ENGLAND JOURNAL OF MEDICINE 293: 152 (1975).
DAVIS, K.L., ENHANCEMENT OF MEMORY BY PHYSOSTIGMINE, NEW ENGLAND JOURNAL OF MEDICINE 301: 946 (1979).
ECKERNAS, S. A., ACTA PHYSIOLOGICA SCANDINAVICA 449: 1 (1977).
ETIENNE, P, LANCET 1: 500 (1978).
ETIENNE, P, LECITHIN IN ALZHEIMERS-DISEASE, LANCET 2: 1206 (1978).
FERRIS, S. H., Combination Choline/Piracetam Treatment of Senile Dementia, PSYCHOPHARMACOLOGY BULLETIN 18: 94 (1982).
FORNO, L. S., JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY 37: 614 (1978).
FROLKIS, V.V., INTERDISCIP TOP GERO 16: 1 (1979).
GIBSON, G.E., NEUROTRANSMITTER AND CARBOHYDRATE-METABOLISM DURING AGING AND MILD HYPOXIA, NEUROBIOLOGY OF AGING 2: 165 (1981). · DOI
GLURGEA, C, CURR DEV PSYCHOPHARM 3: 221 (1976).
HOLBERT, N.M., GERONTOLOGY 1: 131 (1976).
JENSEN, R.A., AGING 1980S PSYCHOL: 191 (1980).
KATZMAN, R, LANCET 2: 1403 (1976).
KUHAR, J.J., BIOL CHOLINERGIC FUN: 3 (1976).
KUTZ, P, BEHAV REV 1: 25 (1977).
LIPPA, A.S., NEUROBIOL AGING 1: 10 (1980).
MARRIOTT, J.G., SOCIETY FOR NEUROSCIENCE. ABSTRACTS 5: 319 (1979).
MORIN, A.M., NEUROCHEM RES 5: 310 (1980).
PALACIOS, J.M., MOL PHARM 16: 1984 (1979).
PERRY, E.K., NORADRENERGIC AND CHOLINERGIC SYSTEMS IN SENILE DEMENTIA OF ALZHEIMER TYPE, LANCET 2: 149 (1981).
RENVOISE, D.G., NEW ENGLAND JOURNAL OF MEDICINE 301: 330 (1979).
SCHMIDT, D.E., NEUROSCIENCE ABSTRACTS 4: 433 (1978).
SIGNORET, J.L., INFLUENCE OF CHOLINE ON AMNESIA IN EARLY ALZHEIMERS-DISEASE, LANCET 2: 837 (1978).
SMITH, C.M., CHOLINE THERAPY IN ALZHEIMERS-DISEASE, LANCET 2: 318 (1978).
SMITH, C.M., LANCET 1: 42 (1979).
VROULIS, G.A., PSYCHOPHARMACOLOGY BULLETIN 17: 127 (1981).
WHITELEY, A, REV NEUROL 135: 565 (1973).
YATES, C.M., DOPAMINE IN ALZHEIMERS-DISEASE AND SENILE DEMENTIA, LANCET 2: 851 (1979).

Sorted by citations

Dementia prevention, intervention, and care
Livingston, G., Sommerlad, A., Orgeta, V., Costafreda, S. G., Huntley, J., Ames, D., Ballard, C., Banerjee, S., Burns, A., Cohen-Mansfield, J., et al. (2017) · The Lancet · doi:10.1016/s0140-6736(17)31363-6 · Cited by 6,072
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies
Long, J. M., & Holtzman, D. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.001 · Cited by 3,204
Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Synapse loss in frontal cortex biopsies in Alzheimer's disease: Correlation with cognitive severity
DeKosky, S. T., & Scheff, S. W. (1990) · Annals of Neurology · doi:10.1002/ana.410270502 · Cited by 2,376
Oxidative stress hypothesis in Alzheimer’s disease
Markesbery, W. R. (1997) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(96)00629-6 · Cited by 2,383
Alzheimer's disease: cell-specific pathology isolates the hippocampal formation.
Hyman, B. T., Van Hoesen, G. W., Damasio, A. R., & Barnes, C. L. (1984) · Science · doi:10.1126/science.6474172 · Cited by 2,268
The cholinergic hypothesis of Alzheimer’s disease: A review of progress
Francis, P. T., Palmer, A. M., Snape, M., & Wilcock, G. K. (1999) · Journal of Neurology, Neurosurgery & Psychiatry · doi:10.1136/jnnp.66.2.137 · Cited by 2,198
Profound Loss of Layer II Entorhinal Cortex Neurons Occurs in Very Mild Alzheimer’s Disease
Gómez-Isla, T., Price, J. L., McKeel Jr., D. W., Morris, J. C., Growdon, J. H., & Hyman, B. T. (1996) · The Journal of Neuroscience · doi:10.1523/jneurosci.16-14-04491.1996 · Cited by 1,796
“From a clinical point of view, the idea that mild memory loss is a common concomitant of aging raises a theoretical model whereby AD and aging lie on a continuous spectrum (Bartus et al., 1982; Brayne and Calloway, 1988).”
Background
Brain Systems that Mediate both Emotion and Cognition
Gray, J. A. (1990) · Cognition & Emotion · doi:10.1080/02699939008410799 · Cited by 1,400
CENTRAL CHOLINERGIC SYSTEMS AND COGNITION
Everitt, B. J., & Robbins, T. W. (1997) · Annual Review of Psychology · doi:10.1146/annurev.psych.48.1.649 · Cited by 1,348
Efficacy of acetylcholinesterase inhibitors in Alzheimer’s disease.
Marucci, G., Buccioni, M., Ben, D. D., Lambertucci, C., Volpini, R., & Amenta, F. (2021) · Neuropharmacology · doi:10.1016/j.neuropharm.2020.108352 · Cited by 1,147
Multi-target-Directed Ligands To Combat Neurodegenerative Diseases
Cavalli, A., Bolognesi, M. L., Minarini, A., Rosini, M., Tumiatti, V., Recanatini, M., & Melchiorre, C. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm7009364 · Cited by 1,152
A phase 1 clinical trial of nerve growth factor gene therapy for Alzheimer disease
Tuszynski, M. H., Thal, L., Pay, M., Salmon, D. P., U, H. S., Bakay, R., Patel, P., Blesch, A., Vahlsing, H. L., Ho, G., et al. (2005) · Nature Medicine · doi:10.1038/nm1239 · Cited by 1,050
Cholinergic systems in mammalian brain and spinal cord
WOOLF, N. (1991) · Progress in Neurobiology · doi:10.1016/0301-0082(91)90006-m · Cited by 948
Skeletal muscle performance and ageing
Tieland, M., Trouwborst, I., & Clark, B. C. (2018) · Journal of Cachexia, Sarcopenia and Muscle · doi:10.1002/jcsm.12238 · Cited by 904
Long-term donepezil treatment in 565 patients with Alzheimer's disease (AD2000): randomised double-blind trial
(2004) · The Lancet · doi:10.1016/s0140-6736(04)16499-4 · Cited by 892
Dynapenia and aging: an update
Manini, T. M., & Clark, B. C. (2012) · The Journals of Gerontology: Series A · doi:10.1093/gerona/glr010 · Cited by 875
On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis
Bartus, R. T. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7397 · Cited by 829
Self-citation
Identification of cells in rat brain and peripheral tissues expressing mRNA for members of the nerve growth factor family
Ernfors, P., Wetmore, C., Olson, L., & Persson, H. (1990) · Neuron · doi:10.1016/0896-6273(90)90090-3 · Cited by 819
Neuron numbers and dendritic extent in normal aging and Alzheimer’s disease
Coleman, P. D., & Flood, D. G. (1987) · Neurobiology of Aging · doi:10.1016/0197-4580(87)90127-8 · Cited by 772
Precursor form of brain-derived neurotrophic factor and mature brain-derived neurotrophic factor are decreased in the pre-clinical stages of Alzheimer’s disease
Peng, S., Wuu, J., Mufson, E. J., & Fahnestock, M. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03135.x · Cited by 691
Current and future treatments for Alzheimer's disease
Yiannopoulou, K. G., & Papageorgiou, S. G. (2013) · Therapeutic Advances in Neurological Disorders · doi:10.1177/1756285612461679 · Cited by 677
Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship
Nelson, P. T., Braak, H., & Markesbery, W. R. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181919a48 · Cited by 643
Brain-Derived Neurotrophic Factor in Alzheimer’s Disease and Its Pharmaceutical Potential
Gao, L., Zhang, Y., Sterling, K., & Song, W. (2022) · Translational Neurodegeneration · doi:10.1186/s40035-022-00279-0 · Cited by 606
Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease
Barage, S. H., & Sonawane, K. D. (2015) · Neuropeptides · doi:10.1016/j.npep.2015.06.008 · Cited by 579
The road to restoring neural circuits for the treatment of Alzheimer's disease
Canter, R. G., Penney, J., & Tsai, L.-H. (2016) · Nature · doi:10.1038/nature20412 · Cited by 565
α 2 -Adrenergic Mechanisms in Prefrontal Cortex Associated with Cognitive Decline in Aged Nonhuman Primates
Arnsten, A. F. T., & Goldman-Rakic, P. S. (1985) · Science · doi:10.1126/science.2999977 · Cited by 549
Alzheimer’s disease: Recent treatment strategies
Vaz, M., & Silvestre, S. (2020) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2020.173554 · Cited by 547
Efficacy and safety of donepezil, galantamine, rivastigmine, and memantine for the treatment of Alzheimer’s disease: A systematic review and meta-analysis
Tan, C.-C., Yu, J.-T., Wang, H.-F., Tan, M.-S., Meng, X.-F., Wang, C., Jiang, T., Zhu, X.-C., & Tan, L. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-132690 · Cited by 484
Progress in studies of huperzine A, a natural cholinesterase inhibitor from Chinese herbal medicine1
WANG, R., YAN, H., & TANG, X.-C. (2006) · Acta Pharmacologica Sinica · doi:10.1111/j.1745-7254.2006.00255.x · Cited by 470
Plasticity of Cortical Excitatory-Inhibitory Balance
Froemke, R. C. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-034002 · Cited by 458
The Cholinergic Lesion of Alzheimer's Disease: Pivotal Factor or Side Show?
Mesulam, M. (2004) · Learning & Memory · doi:10.1101/lm.69204 · Cited by 467
Quantitative assessment of cortical synaptic density in Alzheimer's disease
Scheff, S. W., DeKosky, S. T., & Price, D. A. (1990) · Neurobiology of Aging · doi:10.1016/0197-4580(90)90059-9 · Cited by 446
Cholinergic Switching Within Neocortical Inhibitory Networks
Xiang, Z., Huguenard, J. R., & Prince, D. A. (1998) · Science · doi:10.1126/science.281.5379.985 · Cited by 438
In vivo mapping of cholinergic terminals in normal aging, Alzheimer's disease, and Parkinson's disease
Kuhl, D. E., Minoshima, S., Fessler, J. A., Ficaro, E. P., Wieland, D. M., Koeppe, R. A., Frey, K. A., & Foster, N. L. (1996) · Annals of Neurology · doi:10.1002/ana.410400309 · Cited by 426
The Infectious Etiology of Alzheimer’s Disease
Sochocka, M., Zwolińska, K., & Leszek, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313122937 · Cited by 399
Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome
Lam, B., Masellis, M., Freedman, M., Stuss, D. T., & Black, S. E. (2013) · Alzheimer's Research & Therapy · doi:10.1186/alzrt155 · Cited by 386
Cholinesterase Inhibitors for the Treatment of Alzheimer's Disease:
Grossberg, G. T. (2003) · Current Therapeutic Research · doi:10.1016/s0011-393x(03)00059-6 · Cited by 384
Inflammation and neurodegenerative diseases
Griffin, W. S. T. (2006) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/83.2.470s · Cited by 351
Glucagon‐like peptide‐1 decreases endogenous amyloid‐β peptide (Aβ) levels and protects hippocampal neurons from death induced by Aβ and iron
Perry, T., Lahiri, D. K., Sambamurti, K., Chen, D., Mattson, M. P., Egan, J. M., & Greig, N. H. (2003) · Journal of Neuroscience Research · doi:10.1002/jnr.10611 · Cited by 347
Recent development of multifunctional agents as potential drug candidates for the treatment of Alzheimer’s disease
Guzior, N., Wi.eckowska, A., Panek, D., & Malawska, B. (2014) · Current Medicinal Chemistry · doi:10.2174/0929867321666141106122628 · Cited by 323
Status of Acetylcholinesterase and Butyrylcholinesterase in Alzheimer's Disease and Type 2 Diabetes Mellitus
Mushtaq, G., Greig, N., Khan, J., & Kamal, M. (2014) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/1871527313666141023141545 · Cited by 331
Amyloid β peptide induces tau phosphorylation and loss of cholinergic neurons in rat primary septal cultures
Zheng, W.-H., Bastianetto, S., Mennicken, F., Ma, W., & Kar, S. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00404-9 · Cited by 321
Pharmacokinetics and Pharmacodynamics in Clinical Use of Scopolamine
Renner, U. D., Oertel, R., & Kirch, W. (2005) · Therapeutic Drug Monitoring · doi:10.1097/01.ftd.0000168293.48226.57 · Cited by 314
Genetic Control of Human Brain Transcript Expression in Alzheimer Disease
Webster, J. A., Gibbs, J. R., Clarke, J., Ray, M., Zhang, W., Holmans, P., Rohrer, K., Zhao, A., Marlowe, L., Kaleem, M., et al. (2009) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2009.03.011 · Cited by 304
Piecing together the Puzzle of Basal Forebrain Anatomy
Heimer, L., & Alheid, G. F. (1991) · Advances in Experimental Medicine and Biology · doi:10.1007/978-1-4757-0145-6_1 · Cited by 310
Cholinergic Enhancement and Increased Selectivity of Perceptual Processing During Working Memory
Furey, M. L., Pietrini, P., & Haxby, J. V. (2000) · Science · doi:10.1126/science.290.5500.2315 · Cited by 308
Role of hippocampal oxidative stress in memory deficits induced by sleep deprivation in mice
Silva, R. H., Abílio, V. C., Takatsu, A. L., Kameda, S. R., Grassl, C., Chehin, A. B., Medrano, W. A., Calzavara, M. B., Registro, S., Andersen, M. L., et al. (2004) · Neuropharmacology · doi:10.1016/j.neuropharm.2003.11.032 · Cited by 307
Allosteric Sensitization of Nicotinic Receptors by Galantamine, a New Treatment Strategy for Alzheimer’s Disease
Maelicke, A., Samochocki, M., Jostock, R., Fehrenbacher, A., Ludwig, J., Albuquerque, E. X., & Zerlin, M. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01109-4 · Cited by 303
The role of G protein-coupled receptors in the pathology of Alzheimer's disease
Thathiah, A., & De Strooper, B. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn2977 · Cited by 288
Acetylcholinesterase inhibitors for Alzheimer’s disease: anti-inflammatories in acetylcholine clothing!
Tabet, N. (2006) · Age and Ageing · doi:10.1093/ageing/afl027 · Cited by 285
The nature of learning and memory impairments in schizophrenia
Paulsen, J. S., Heaton, R. K., Sadek, J. R., Perry, W., Delis, D. C., Braff, D., Kuck, J., Zisook, S., & Jeste, D. V. (1995) · Journal of the International Neuropsychological Society · doi:10.1017/s135561770000014x · Cited by 284
A Comprehensive Behavioral Test Battery to Assess Learning and Memory in 129S6/Tg2576 Mice
Wolf, A., Bauer, B., Abner, E. L., Ashkenazy-Frolinger, T., & Hartz, A. M. S. (2016) · PLOS ONE · doi:10.1371/journal.pone.0147733 · Cited by 281
“Scopolamine-induced dementia has been studied in rodents and humans, but no work has been published on scopolamine-induced dementia in 129S6 mice [42, 43].”
Background
Muscarinic cholinergic influences in memory consolidation
Power, A. (2003) · Neurobiology of Learning and Memory · doi:10.1016/s1074-7427(03)00086-8 · Cited by 261
The Role of Estrogen in Brain and Cognitive Aging
Russell, J. K., Jones, C. K., & Newhouse, P. A. (2019) · Neurotherapeutics · doi:10.1007/s13311-019-00766-9 · Cited by 257
The exercise-induced expression of BDNF within the hippocampus varies across life-span
Adlard, P. A., Perreau, V. M., & Cotman, C. W. (2005) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.05.006 · Cited by 260
New approach to the diagnosis of growth hormone deficiency in adults
Ghigo, E., Aimaretti, G., Gianotti, L., Bellone, J., Arvat, E., & Camanni, F. (1996) · European Journal of Endocrinology · doi:10.1530/eje.0.1340352 · Cited by 257
The metabolic topography of normal aging
Moeller, J. R., Ishikawa, T., Dhawan, V., Spetsieris, P., Mandel, F., Alexander, G. E., Grady, C., Pietrini, P., & Eidelberg, D. (1996) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199605000-00005 · Cited by 254
An atlas of the regional and laminar distribution of choline acetyltransferase immunoreactivity in rat cerebral cortex
Lysakowski, A., Wainer, B. H., Bruce, G., & Hersh, L. B. (1989) · Neuroscience · doi:10.1016/0306-4522(89)90180-2 · Cited by 239
The cholinergic system and hippocampal plasticity
Drever, B. D., Riedel, G., & Platt, B. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.037 · Cited by 240
Vitamin A deficiency produces spatial learning and memory impairment in rats
Cocco, S., Diaz, G., Stancampiano, R., Diana, A., Carta, M., Curreli, R., Sarais, L., & Fadda, F. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00423-2 · Cited by 231
A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer’s disease
Rafii, M. S., Baumann, T. L., Bakay, R. A. E., Ostrove, J. M., Siffert, J., Fleisher, A. S., Herzog, C. D., Barba, D., Pay, M., Salmon, D. P., et al. (2014) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2013.09.004 · Cited by 223
Self-citation
Adeno-Associated Viral Vector (Serotype 2)–Nerve Growth Factor for Patients With Alzheimer Disease: A Randomized Clinical Trial
Rafii, M. S., Tuszynski, M. H., Thomas, R. G., Barba, D., Brewer, J. B., Rissman, R. A., Siffert, J., Aisen, P. S., & for the AAV2-NGF Study Team (2018) · JAMA Neurology · doi:10.1001/jamaneurol.2018.0233 · Cited by 219
Neurophysiological and neuropsychological evidence for attentional dysfunction in schizophrenia
Cullum, C. M., Harris, J. G., Waldo, M. C., Smernoff, E., Madison, A., Nagamoto, H. T., Griffith, J., Adler, L. E., & Freedman, R. (1993) · Schizophrenia Research · doi:10.1016/0920-9964(93)90048-n · Cited by 212
Cholinesterase Inhibitors and Beyond
Pepeu, G., & Giovannini, M. (2009) · Current Alzheimer Research · doi:10.2174/156720509787602861 · Cited by 209
Neuronal nicotinic receptors: A perspective on two decades of drug discovery research
Arneric, S. P., Holladay, M., & Williams, M. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.06.033 · Cited by 208
Preferential Localization of Muscarinic M1Receptor on Dendritic Shaft and Spine of Cortical Pyramidal Cells and Its Anatomical Evidence for Volume Transmission
Yamasaki, M., Matsui, M., & Watanabe, M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.5719-09.2010 · Cited by 203
Excitotoxic lesions of basal forebrain cholinergic neurons: Effects on learning, memory and attention
Muir, J. L., Page, K. J., Sirinathsinghji, D. J. S., Robbins, T. W., & Everitt, B. J. (1993) · Behavioural Brain Research · doi:10.1016/0166-4328(93)90128-d · Cited by 199
Cholinergic stimulation enhances long-term potentiation in the CA1 region of rat hippocampus
Blitzer, R. D., Gil, O., & Landau, E. M. (1990) · Neuroscience Letters · doi:10.1016/0304-3940(90)90835-w · Cited by 192
Neuromodulation by acetylcholine: examples from schizophrenia and depression
Higley, M. J., & Picciotto, M. R. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.06.004 · Cited by 184
Reimagining cholinergic therapy for Alzheimer’s disease
Giacobini, E., Cuello, A. C., & Fisher, A. (2022) · Brain · doi:10.1093/brain/awac096 · Cited by 187
Topography of Cross-sectional and Longitudinal Glucose Metabolic Deficits in Alzheimer's Disease: Pathophysiologic Implications
Smith, G. S. (1992) · Archives of Neurology · doi:10.1001/archneur.1992.00530350056020 · Cited by 178
Cholinergic deficits contribute to behavioral disturbance in patients with dementia
Minger, S. L., Esiri, M. M., McDonald, B., Keene, J., Carter, J., Hope, T., & Francis, P. T. (2000) · Neurology · doi:10.1212/wnl.55.10.1460 · Cited by 176
The Possibility of an Infectious Etiology of Alzheimer Disease
Ashraf, G. M., Tarasov, V. V., Makhmutovа, A., Chubarev, V. N., Avila-Rodriguez, M., Bachurin, S. O., & Aliev, G. (2019) · Molecular Neurobiology · doi:10.1007/s12035-018-1388-y · Cited by 175
From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology
Albertini, C., Salerno, A., de Sena Murteira Pinheiro, P., & Bolognesi, M. L. (2021) · Medicinal Research Reviews · doi:10.1002/med.21699 · Cited by 179
Cholinergic Changes in the APP23 Transgenic Mouse Model of Cerebral Amyloidosis
Boncristiano, S., Calhoun, M. E., Kelly, P. H., Pfeifer, M., Bondolfi, L., Stalder, M., Phinney, A. L., Abramowski, D., Sturchler-Pierrat, C., Enz, A., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-08-03234.2002 · Cited by 160
The art of building multifunctional metal-binding agents from basic molecular scaffolds for the potential application in neurodegenerative diseases
Rodríguez-Rodríguez, C., Telpoukhovskaia, M., & Orvig, C. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.03.008 · Cited by 151
Cholinergic modulation of excitatory synaptic transmission in the CA3 area of the hippocampus
Vogt, K. E., & Regehr, W. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-01-00075.2001 · Cited by 149
Efficacy, safety and tolerability of rivastigmine capsules in patients with probable vascular dementia: the VantagE study
Ballard, C., Sauter, M., Scheltens, P., He, Y., Barkhof, F., van Straaten, E. C. W., van der Flier, W. M., Hsu, C., Wu, S., & Lane, R. (2008) · Current Medical Research and Opinion · doi:10.1185/03007990802328142 · Cited by 147
Basal forebrain cholinergic signalling: development, connectivity and roles in cognition
Ananth, M. R., Rajebhosale, P., Kim, R., Talmage, D. A., & Role, L. W. (2023) · Nature Reviews Neuroscience · doi:10.1038/s41583-023-00677-x · Cited by 148
Nicotinic treatment of Alzheimer’s disease
Newhouse, P. A., Potter, A., Kelton, M., & Corwin, J. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(00)01069-6 · Cited by 146
Adding fuel to the fire: the impact of stress on the ageing brain
Prenderville, J. A., Kennedy, P. J., Dinan, T. G., & Cryan, J. F. (2015) · Trends in Neurosciences · doi:10.1016/j.tins.2014.11.001 · Cited by 136
Cholinergic nerve terminals establish classical synapses in the rat cerebral cortex: synaptic pattern and age-related atrophy
Turrini, P., Casu, M. A., Wong, T. P., De Koninck, Y., Ribeiro-da-Silva, A., & Cuello, A. C. (2001) · Neuroscience · doi:10.1016/s0306-4522(01)00172-5 · Cited by 135
Clinical Pharmacokinetics of Galantamine
Farlow, M. R. (2003) · Clinical Pharmacokinetics · doi:10.2165/00003088-200342150-00005 · Cited by 134
The Coming of Age of the Angiotensin Hypothesis in Alzheimer’s Disease: Progress Toward Disease Prevention and Treatment?
Kehoe, P. G. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171119 · Cited by 133
Communication breaks-Down: From neurodevelopment defects to cognitive disabilities in Down syndrome
Contestabile, A., Benfenati, F., & Gasparini, L. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.01.003 · Cited by 134
Choline Alphoscerate in Cognitive Decline and in Acute Cerebrovascular Disease: An Analysis of Published Clinical Data
Parnetti, L., Amenta, F., & Gallai, V. (2001) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(01)00312-8 · Cited by 132
The human basal forebrain. Part II
Heimer, L., de Olmos, J. S., Alheid, G. F., Pearson, J., Sakamoto, N., Shinoda, K., Marksteiner, J., & Switzer, R. C. (1999) · Handbook of Chemical Neuroanatomy · doi:10.1016/s0924-8196(99)80024-4 · Cited by 125
Neuronal Circuitry Mechanisms Regulating Adult Mammalian Neurogenesis
Song, J., Olsen, R. H. J., Sun, J., Ming, G.-L., & Song, H. (2016) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a018937 · Cited by 125
Molecular mechanisms of brain-derived neurotrophic factor in neuro-protection: Recent developments
Zhao, H., Alam, A., San, C.-Y., Eguchi, S., Chen, Q., Lian, Q., & Ma, D. (2017) · Brain Research · doi:10.1016/j.brainres.2017.03.029 · Cited by 122
Role of Serotonin in Alzheimerʼs Disease: A New Therapeutic Target?
Geldenhuys, W. J., & Van der Schyf, C. J. (2011) · CNS Drugs · doi:10.2165/11590190-000000000-00000 · Cited by 117
Clitoria ternatea root extract enhances acetylcholine content in rat hippocampus
Rai, K. S., Murthy, K. D., Karanth, K. S., Nalini, K., Rao, M. S., & Srinivasan, K. K. (2002) · Fitoterapia · doi:10.1016/s0367-326x(02)00249-6 · Cited by 113
Novel tacrine-tryptophan hybrids: Multi-target directed ligands as potential treatment for Alzheimer's disease
Chalupova, K., Korabecny, J., Bartolini, M., Monti, B., Lamba, D., Caliandro, R., Pesaresi, A., Brazzolotto, X., Gastellier, A.-J., Nachon, F., et al. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.02.021 · Cited by 118
Hippocampal memory enhancing activity of pine needle extract against scopolamine-induced amnesia in a mouse model
Lee, J.-S., Kim, H.-G., Lee, H.-W., Han, J.-M., Lee, S.-K., Kim, D.-W., Saravanakumar, A., & Son, C.-G. (2015) · Scientific Reports · doi:10.1038/srep09651 · Cited by 110
Acetylcholinesterase Inhibitory Potential of Various Sesquiterpene Analogues for Alzheimer’s Disease Therapy
Arya, A., Chahal, R., Rao, R., Rahman, M. H., Kaushik, D., Akhtar, M. F., Saleem, A., Khalifa, S. M. A., El-Seedi, H. R., Kamel, M., et al. (2021) · Biomolecules · doi:10.3390/biom11030350 · Cited by 111
“It has also been observed that cholinergic neurons are highly damaged in the forebrain during the progression of AD [16,17].”
Background
PET Neuroimaging of Alzheimer's Disease: Radiotracers and Their Utility in Clinical Research
Bao, W., Xie, F., Zuo, C., Guan, Y., & Huang, Y. H. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.624330 · Cited by 102
Aged Non‐Human Primates: An Animal Model of Age‐Associated Neurodegenerative Disease
Price, D. L., Martin, L. J., Sisodia, S. S., Wagster, M. V., Koo, E. H., Walker, L. C., Koliatsos, V. E., & Cork, L. C. (1991) · Brain Pathology · doi:10.1111/j.1750-3639.1991.tb00672.x · Cited by 100
Clinical tests of neurotrophic factors for human neurodegenerative diseases, part 1: Where have we been and what have we learned?
Bartus, R. T., & Johnson, E. M. (2017) · Neurobiology of Disease · doi:10.1016/j.nbd.2016.03.027 · Cited by 97
Self-citation
Single-Cell Gene Expression Analysis: Implications for Neurodegenerative and Neuropsychiatric Disorders
Ginsberg, S. D., Elarova, I., Ruben, M., Tan, F., Counts, S. E., Eberwine, J. H., Trojanowski, J. Q., Hemby, S. E., Mufson, E. J., & Che, S. (2004) · Neurochemical Research · doi:10.1023/b:nere.0000023593.77052.f7 · Cited by 97
Effects of cholinergic drugs on delayed match-to-sample performance of rhesus monkeys
Penetar, D. M., & McDonough, J. H. (1983) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(83)90399-4 · Cited by 96

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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The Cholinergic Hypothesis of Geriatric Memory Dysfunction

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks