On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis

Bartus, Raymond T.

doi:10.1006/exnr.2000.7397

Cited by 853Alzheimer's disease research and treatmentsCholinesterase and Neurodegenerative DiseasesDementia and Cognitive Impairment Research

On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis

Bartus, Raymond T.·2000·Experimental Neurology

DOI 10.1006/exnr.2000.7397

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Abstract

Life's Journey If life is indeed a journey, then poetry must be the map that reveals all its topographic possibilitiesellipsis while science is the compass that keeps us from getting lost. -R. T. Bartus, Simple Words for Complex Lives, (c) 1998 In the nearly 20 years since the cholinergic hypothesis was initially formulated, significant progress has been achieved. Initial palliative treatments for Alzheimer's disease (AD) have proven beneficial and have gained FDA approval, the use of animal models for studying AD and other neurodegenerative diseases has achieved wider acceptance, and important insight into the potential causes and pathogenic variables associated with various neurodegenerative diseases continues to increase. This paper reviews the current status of the cholinergic hypothesis in the context of continuing efforts to improve upon existing treatments for AD and explores the role that animal models might continue to play. Using the benefit of hindsight, particular emphasis is placed on an analysis of the approaches, strategies, and assumptions regarding animal models that proved useful in developing the initial treatments and those that did not. Additionally, contemporary issues of AD are discussed within the context of the cholinergic hypothesis, with particular attention given to how they may impact the further refinement of animal models, and the development of even more effective treatments. Finally, arguments are presented that, despite the deserved enthusiasm and optimism for identifying means of halting the pathogenesis of AD, a clear need for more effective palliative treatments will continue, long after successful pathogenic treatments are available. This review, therefore, focuses on issues and experiences intended to: (a) facilitate further development and use of animal models for AD and other neurodegenerative diseases, and (b) accelerate the identification of newer, even more effective treatments.

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Abnormalities in cholinergic activity profoundly impair cortical and hippocampal information processing.
“The anatomical organization of this neuronal system predicts that abnormalities in cholinergic activity profoundly impairs cortical and hippocampal information processing (e.g., Bartus, 2000; Mesulam, 2004; Sarter et al, 2005a).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Bartus, 2000

Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,841 · see citing works
The cholinergic hypothesis of geriatric memory dysfunction
Bartus, R. T., Dean, R. L., Beer, B., & Lippa, A. S. (1982) · Science · doi:10.1126/science.7046051 · Cited by 5,545 · see citing works
Self-citation
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 · see citing works
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 · see citing works
Psychopharmacology: The third generation of progress
O’Connell, R. A. (1988) · Comprehensive Psychiatry · doi:10.1016/0010-440x(88)90057-0 · Cited by 3,014 · see citing works
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 · see citing works
A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer's disease
Rogers, S. L., Farlow, M. R., Doody, R. S., Mohs, R., Friedhoff, L. T., & Donepezil Study Group* (1998) · Neurology · doi:10.1212/wnl.50.1.136 · Cited by 1,618 · see citing works
Human Memory and the Cholinergic System
Drachman, D. A. (1974) · Archives of Neurology · doi:10.1001/archneur.1974.00490320001001 · Cited by 1,398 · see citing works
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 · see citing works
APRIORITY
Asher, R. (1961) · The Lancet · doi:10.1016/s0140-6736(61)91217-x · Cited by 1,290 · see citing works
Memory in monkeys severely impaired by combined but not by separate removal of amygdala and hippocampus
Mishkin, M. (1978) · Nature · doi:10.1038/273297a0 · Cited by 1,207 · see citing works
Oral Tetrahydroaminoacridine in Long-Term Treatment of Senile Dementia, Alzheimer Type
Summers, W. K., Majovski, L. V., Marsh, G. M., Tachiki, K. H., & Kling, A. S. (1986) · New England Journal of Medicine · doi:10.1056/nejm198611133152001 · Cited by 1,161 · see citing works
The prefrontal landscape: implications of functional architecture for understanding human mentation and the central executive
Goldman-Rakic, P. S. (1996) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1996.0129 · Cited by 1,072 · see citing works
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 · see citing works
Efficacy and safety of rivastigmine in patients with Alzheimer's disease: international randomised controlled trial Commentary: Another piece of the Alzheimer's jigsaw
Rosler, M., Anand, R., Cicin-Sain, A., Gauthier, S., Agid, Y., Dal-Bianco, P., Stahelin, H. B., Hartman, R., Gharabawi, M., & Bayer, T. (1999) · BMJ · doi:10.1136/bmj.318.7184.633 · Cited by 943 · see citing works
Estrogen Therapy in Postmenopausal Women
Yaffe, K. S., Sawaya, G. F., Lieberburg, I. M., & Grady, D. G. (1998) · JAMA · doi:10.1001/jama.279.9.688 · Cited by 941 · see citing works
Age‐associated memory impairment: Proposed diagnostic criteria and measures of clinical change — report of a national institute of mental health work group
Crook, T. H., Bartus, R. T., Ferris, S. H., Whitehouse, P. J., Cohen, G. D., & Gershon, S. (1986) · Developmental Neuropsychology · doi:10.1080/87565648609540348 · Cited by 930 · see citing works
Self-citation
Senile dementia of the Alzheimer type
Terry, R. D., & Katzman, R. (1983) · Annals of Neurology · doi:10.1002/ana.410140502 · Cited by 831 · see citing works
Alzheimer's Disease: Senile Dementia and Related Disorders
Bellur, S. N. (1979) · JAMA · doi:10.1001/jama.1979.03300200059031 · Cited by 804 · see citing works
Brain mechanisms and intelligence: A quantitative study of injuries to the brain.
Lashley, K. S. (1929) · University of Chicago Press eBooks · doi:10.1037/10017-000 · Cited by 744 · see citing works
The Cholinergic Synapse and the Site of Memory
Deutsch, J. A. (1972) · Advances in behavioral biology · doi:10.1007/978-1-4684-3060-8_11 · Cited by 740 · see citing works
The Cholinergic Synapse and the Site of Memory
Deutsch, J. A. (1971) · Science · doi:10.1126/science.174.4011.788 · Cited by 662 · see citing works
A Double-Blind, Placebo-Controlled Multicenter Study of Tacrine for Alzheimer's Disease
Davis, K. L., Thal, L. J., Gamzu, E. R., Davis, C. S., Woolson, R. F., Gracon, S. I., Drachman, D. A., Schneider, L. S., Whitehouse, P. J., Hoover, T. M., et al. (1992) · New England Journal of Medicine · doi:10.1056/nejm199210293271801 · Cited by 626 · see citing works
Behavior: An introduction to comparative psychology.
Watson, J. B. (1914) · Henry Holt and Company eBooks · doi:10.1037/10868-000 · Cited by 606 · see citing works
Cholinergic mechanisms in learning, memory and dementia: a review of recent evidence
Fibiger, H. C. (1991) · Trends in Neurosciences · doi:10.1016/0166-2236(91)90117-d · Cited by 599 · see citing works
Estrogen Replacement Therapy in Older Women
Henderson, V. W. (1994) · Archives of Neurology · doi:10.1001/archneur.1994.00540210068014 · Cited by 590 · see citing works
α <sub>2</sub> -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 · see citing works
The Effects of Nicotine on Attention, Information Processing, and Short-Term Memory in Patients with Dementia of the Alzheimer Type
Sahakian, B. J., Jones, G., Levy, R., Gray, J. A., & Warburton, D. M. (1989) · The British Journal of Psychiatry · doi:10.1192/bjp.154.6.797 · Cited by 494 · see citing works
Cholinergic Markers in Elderly Patients With Early Signs of Alzheimer Disease
Davis, K. L. (1999) · JAMA · doi:10.1001/jama.281.15.1401 · Cited by 492 · see citing works
Spatial memory deficit in senescent rats.
Barnes, C. A., Nadel, L., & Honig, W. K. (1980) · Canadian Journal of Psychology/Revue Canadienne de Psychologie · doi:10.1037/h0081022 · Cited by 487 · see citing works
Nicotinic acetylcholine binding sites in Alzheimer's disease
Whitehouse, P. J., Martino, A. M., Antuono, P., Lowenstein, P. R., Coyle, J. T., Price, D. L., & Kellar, K. J. (1986) · Brain Research · doi:10.1016/0006-8993(86)90819-x · Cited by 485 · see citing works
Basal forebrain lesions in monkeys disrupt attention but not learning and memory [published erratum appears in J Neurosci 1995 Mar;15(3): following table of contents]
Voytko, M. L., Olton, D. S., Richardson, R., Gorman, L. K., Tobin, J., & Price, D. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-01-00167.1994 · Cited by 483 · see citing works
Effects of acute subcutaneous nicotine on attention, information processing and short-term memory in alzheimer's disease
Jones, G., Sahakian, B. J., Levy, R., Warburton, D. M., & Gray, J. A. (1992) · Psychopharmacology · doi:10.1007/bf02247426 · Cited by 476 · see citing works
Function of neurotrophic factors in the adult and aging brain and their possible use in the treatment of neurodegenerative diseases
Hefti, F., Hartikka, J., & Knusel, B. (1989) · Neurobiology of Aging · doi:10.1016/0197-4580(89)90118-8 · Cited by 466 · see citing works
The basal forebrain-cortical cholinergic system: interpreting the functional consequences of excitotoxic lesions
Dunnett, S. B., Everitt, B. J., & Robbins, T. W. (1991) · Trends in Neurosciences · doi:10.1016/0166-2236(91)90061-x · Cited by 460 · see citing works
The Predictive Value of Changes in Effective Connectivity for Human Learning
Büchel, C., Coull, J. T., & Friston, K. J. (1999) · Science · doi:10.1126/science.283.5407.1538 · Cited by 447 · see citing works
Physostigmine: Improvement of Long-Term Memory Processes in Normal Humans
Davis, K. L., Mohs, R. C., Tinklenberg, J. R., Pfefferbaum, A., Hollister, L. E., & Kopell, B. S. (1978) · Science · doi:10.1126/science.351807 · Cited by 442 · see citing works
Treatment of Alzheimer's Disease
Mayeux, R. P., & Sano, M. C. (1999) · New England Journal of Medicine · doi:10.1056/nejm199911253412207 · Cited by 389 · see citing works
Alteration in nicotine binding sites in Parkinson's disease, Lewy body dementia and Alzheimer's disease: Possible index of early neuropathology
Perry, E. K., Morris, C. M., COURT, J. A., Cheng, A. V., FAIRBAIRN, A. F., McKeith, I. G., Irving, D., Brown, A. J., & Perry, R. H. (1995) · Neuroscience · doi:10.1016/0306-4522(94)00410-7 · Cited by 386 · see citing works
BEHAVIORAL AND ELECTROENCEPHALOGRAPHIC EFFECTS OF ATROPINE AND RELATED COMPOUNDS
Longo, V. G. (1966) · Pharmacological Reviews · doi:10.1016/s0031-6997(25)07156-x · Cited by 385 · see citing works
The Cholinergic Hypothesis: A Historical Overview, Current Perspective, and Future Directions
Bartus, R. T., Dean, R. L., Pontecorvo, M. J., & Flicker, C. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb37600.x · Cited by 384 · see citing works
Self-citation
Alzheimer's disease : senile dementia and related disorders
Disorders, B. R., Katzman, R., Terry, R. D., & Bick, K. L. (1978) · Raven Press eBooks · Cited by 377 · see citing works
Behavioral and neurochemical effects following neurotoxic lesions of a major cholinergic input to the cerebral cortex in the rat1
Flicker, C., DEAN, R., Watkins, D. L., FISHER, S., & Bartus, R. T. (1983) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(83)80023-9 · Cited by 370 · see citing works
Self-citation
Reduced number of [3H]nicotine and [3H]acetylcholine binding sites in the frontal cortex of Alzheimer brains
Nordberg, A. K., & Winblad, B. G. (1986) · Neuroscience Letters · doi:10.1016/0304-3940(86)90629-4 · Cited by 361 · see citing works
Physostigmine and Arecoline: Effects of Intravenous Infusions in Alzheimer Presenile Dementia
CHRISTIE, J. E., Shering, A., Ferguson, J. M., & Glen, A. I. M. (1981) · The British Journal of Psychiatry · doi:10.1192/bjp.138.1.46 · Cited by 360 · see citing works
Cognitive functions of the basal forebrain
Baxter, M. G., & Chiba, A. A. (1999) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(99)80024-5 · Cited by 351 · see citing works
Behavioural, biochemical and histochemical effects of different neurotoxic amino acids injected into nucleus basalis magnocellularis of rats
Dunnett, S. B., Whishaw, I. Q., Jones, G. H., & Bunch, S. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90117-5 · Cited by 349 · see citing works
Age-related learning deficits in transgenic mice expressing the 751-amino acid isoform of human beta-amyloid precursor protein.
Moran, P. M., Higgins, L. S., Cordell, B., & Moser, P. C. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5341 · Cited by 338 · see citing works
Brain acetylcholine: Increase after systematic choline administration
Cohen, E. L., & Wurtman, R. J. (1975) · Life Sciences · doi:10.1016/0024-3205(75)90194-0 · Cited by 336 · see citing works
Short-term memory in the rhesus monkey: Disruption from the anti-cholinergic scopolamine
Bartus, R. T., & Johnson, H. R. (1976) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(76)90286-0 · Cited by 334 · see citing works
Self-citation
Differential effects on spatial navigation of immunotoxin-induced cholinergic lesions of the medial septal area and nucleus basalis magnocellularis
Berger-Sweeney, J. E., Heckers, S., Mesulam, M. M., Wiley, R. G., Lappi, D., & Sharma, M. C. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-07-04507.1994 · Cited by 327 · see citing works
Stable Complexes Involving Acetylcholinesterase and Amyloid-β Peptide Change the Biochemical Properties of the Enzyme and Increase the Neurotoxicity of Alzheimer’s Fibrils
Alvarez, A. R., Alarcón, R., Opazo, C., Campos, E. O., Muñoz, F. J., Calderón, F. H., Dajas, F., Gentry, M. K., Doctor, B. P., Mello, F. G. D., et al. (1998) · Journal of Neuroscience · doi:10.1523/jneurosci.18-09-03213.1998 · Cited by 320 · see citing works
Acetylcholinesterase promotes the aggregation of amyloid-beta-peptide fragments by forming a complex with the growing fibrils.
Álvarez, A., Opazo, C., Alarcón, R., Garrido, J., & Inestrosa, N. (1997) · Journal of Molecular Biology · doi:10.1006/jmbi.1997.1245 · Cited by 308 · see citing works
Changes of Biogenic Amines and Their Metabolites in Postmortem Brains from Patients with Alzheimer‐Type Dementia
Aral, H., Kosaka, K., & Iizuka, R. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb00913.x · Cited by 308 · see citing works
Mechanisms of memory
John, E. (1967) · Academic Press eBooks · Cited by 304 · see citing works
Progressive decline in spatial learning and integrity of forebrain cholinergic neurons in rats during aging
Fischer, W., Chen, K. S., Gage, F. H., & Björklund, A. (1992) · Neurobiology of Aging · doi:10.1016/0197-4580(92)90003-g · Cited by 293 · see citing works
Long-term tacrine (Cognex) treatment
Knopman, D. S., Schneider, L. S. S., Davis, K. L., Talwalker, S., Smith, F., Hoover, T. M., & Gracon, S. I. (1996) · Neurology · doi:10.1212/wnl.47.1.166 · Cited by 293 · see citing works
Aging in the Rhesus Monkey: Debilitating Effects on Short-term Memory
Bartus, R. T., Fleming, D., & Johnson, H. R. (1978) · Journal of Gerontology · doi:10.1093/geronj/33.6.858 · Cited by 284 · see citing works
Self-citation
Characterization of l ‐[3H]Nicotine Binding in Human Cerebral Cortex: Comparison Between Alzheimer's Disease and the Normal
Flynn, D. D., & Mash, D. C. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb13113.x · Cited by 284 · see citing works
Evidence for task-dependent memory dysfunction in the aged monkey
Rapp, P. R., & Amaral, D. (1989) · Journal of Neuroscience · doi:10.1523/jneurosci.09-10-03568.1989 · Cited by 277 · see citing works
Age-Related Changes in Passive Avoidance Retention: Modulation with Dietary Choline
Bartus, R. T., Dean, R. L., Goas, J. A., & LIPPA, A. S. (1980) · Science · doi:10.1126/science.7384805 · Cited by 275 · see citing works
Self-citation
Enhancement of memory processes in Alzheimer's disease with multiple- dose intravenous physostigmine
Davis, K. L., & Mohs, R. C. (1982) · American Journal of Psychiatry · doi:10.1176/ajp.139.11.1421 · Cited by 268 · see citing works
Reduced dopamine-beta-hydroxylase activity in Alzheimer's disease
Cross, A. J., Crow, T. J., Perry, E. K., Perry, R. H., Blessed, G., & Tomlinson, B. E. (1981) · BMJ · doi:10.1136/bmj.282.6258.93 · Cited by 267 · see citing works
Aged monkeys exhibit behavioral deficits indicative of widespread cerebral dysfunction
Bachevalier, J., Landis, L. S., Walker, L. C., Brickson, M., Mishkin, M., Price, D. L., & Cork, L. C. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90048-o · Cited by 264 · see citing works
The 36-hour day
Mace, N. L. (1981) · Cited by 261 · see citing works
Aging in the 1980's: Psychological Issues
Sinnott, J. D. (1981) · Journal of Gerontology · doi:10.1093/geronj/36.2.251 · Cited by 260 · see citing works
Brain cholinergic dysfunction and memory in aged rats
LIPPA, A. S., Pelham, R. W., Beer, B., Critchett, D. J., DEAN, R., & Bartus, R. T. (1980) · Neurobiology of Aging · doi:10.1016/0197-4580(80)90019-6 · Cited by 257 · see citing works
Self-citation
Dopamine D2 receptor mechanisms contribute to age-related cognitive decline: the effects of quinpirole on memory and motor performance in monkeys
Arnsten, A. F. T., Cai, J., Steere, J. C., & Goldman-Rakic, P. S. (1995) · Journal of Neuroscience · doi:10.1523/jneurosci.15-05-03429.1995 · Cited by 254 · see citing works
Spatial learning deficits in old rats: A model for memory decline in the aged
Gallagher, M., & Pelleymounter, M. A. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80112-x · Cited by 253 · see citing works
Behavioral, biochemical, histological, and electrophysiological effects of 192 IgG-saporin injections into the basal forebrain of rats
Wenk, G. L., Stoehr, J. D., Quintana, G., Mobley, S., & Wiley, R. G. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-10-05986.1994 · Cited by 252 · see citing works
Patterns of memory failure after scopolamine treatment: Implications for cholinergic hypotheses of dementia
Beatty, W. W., Butters, N., & Janowsky, D. S. (1986) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(86)90772-7 · Cited by 249 · see citing works
Selective memory loss following nucleus basalis lesions: Long term behavioral recovery despite persistent cholinergic deficiencies
Bartus, R. T., Flicker, C., Dean, R. L., Pontecorvo, M. J., Figueiredo, J. C., & Fisher, S. K. (1985) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(85)90139-x · Cited by 247 · see citing works
Self-citation
Age-associated neuronal atrophy occurs in the primate brain and is reversible by growth factor gene therapy
Smith, D. E., Roberts, J. A., Gage, F. H., & Tuszynski, M. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.19.10893 · Cited by 244 · see citing works
Oral physostigmine treatment of patients with Alzheimer's disease
Mohs, R. C., Davis, B. J., Johns, C. A., Mathé, A. A., GREENWALD, B. S., Horvath, T., & Davis, K. L. (1985) · American Journal of Psychiatry · doi:10.1176/ajp.142.1.28 · Cited by 240 · see citing works
Disruption of a Single Allele of the Nerve Growth Factor Gene Results in Atrophy of Basal Forebrain Cholinergic Neurons and Memory Deficits
Chen, K. S., Nishimura, M. C., Armanini, M. P., Crowley, C. W., Spencer, S. D., & PHILLIPS, H. S. (1997) · Journal of Neuroscience · doi:10.1523/jneurosci.17-19-07288.1997 · Cited by 227 · see citing works
Aging and the physiology of spatial memory
Barnes, C. A. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80114-3 · Cited by 223 · see citing works
Age-related behavioral and neurobiological changes: A review with an emphasis on memory
Kubanis, P., & Zornetzer, S. F. (1981) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(81)91195-x · Cited by 222 · see citing works
Ageing: the cholinergic hypothesis of cognitive decline
Gallagher, M., & Colombo, P. J. (1995) · Current Opinion in Neurobiology · doi:10.1016/0959-4388(95)80022-0 · Cited by 212 · see citing works
Enhancement by an Ampakine of Memory Encoding in Humans
Ingvar, M., Ambros‐Ingerson, J., Davis, M., Granger, R., Kessler, M., Rogers, G. A., Schehr, R. S., & LYNCH, G. S. (1997) · Experimental Neurology · doi:10.1006/exnr.1997.6581 · Cited by 211 · see citing works
Brain Acetylcholine and Neuropsychiatric Disease
Davis, K. L., & Berger, P. A. (1979) · Springer eBooks · doi:10.1007/978-1-4613-2934-3 · Cited by 210 · see citing works
Behavior: an Introduction to Comparative Psychology.
Washburn, M. F., & Watson, J. B. (1915) · The Philosophical Review · doi:10.2307/2178235 · Cited by 208 · see citing works
Physostigmine and Recent Memory: Effects in Young and Aged Nonhuman Primates
Bartus, R. T. (1979) · Science · doi:10.1126/science.227061 · Cited by 207 · see citing works
Self-citation
Age-related differences in behavior across the life span of the C57BL/6J mouse
Dean, R. L., Scozzafava, J., Goas, J. A., Regan, B., Beer, B., & Bartus, R. T. (1981) · Experimental Aging Research · doi:10.1080/03610738108259823 · Cited by 200 · see citing works
Self-citation
Treatment Development Strategies for Alzheimer’s Disease
Seelye, E. E. (1987) · American Journal of Psychotherapy · doi:10.1176/appi.psychotherapy.1987.41.4.622 · Cited by 199 · see citing works
Relation between nicotine intake and Alzheimer's disease.
van Duijn, C. M., & Hofman, A. (1991) · BMJ · doi:10.1136/bmj.302.6791.1491 · Cited by 198 · see citing works
β-Amyloid peptides as direct cholinergic neuromodulators: a missing link?
Auld, D. S., Kar, S., & Quirion, R. (1998) · Trends in Neurosciences · doi:10.1016/s0166-2236(97)01144-2 · Cited by 192 · see citing works
Reductions in [ 3 H]nicotinic acetylcholine binding in Alzheimer's disease and Parkinson's disease
Whitehouse, P. J., Martino, A. M., Wagster, M. V., Price, D. L., Mayeux, R. P., Atack, J. R., & Kellar, K. J. (1988) · Neurology · doi:10.1212/wnl.38.5.720 · Cited by 185 · see citing works
Aging in the Rhesus Monkey: Effects on Visual Discrimination Learning and Reversal Learning
Bartus, R. T., Dean, R. L., & Fleming, D. L. (1979) · Journal of Gerontology · doi:10.1093/geronj/34.2.209 · Cited by 185 · see citing works
Self-citation
Increased cognitive sensitivity to scopolamine with age and a perspective on the scopolamine model
Molchan, S. E., Martínez, R. A., Hill, J., Weingartner, H. J., Thompson, K., Vitiello, B., & Sunderland, T. (1992) · Brain Research Reviews · doi:10.1016/0165-0173(92)90017-g · Cited by 184 · see citing works
Evidence for a direct cholinergic involvement in the scopolamine-induced amnesia in monkeys: Effects of concurrent administration of physostigmine and methylphenidate with scopolamine
Bartus, R. T. (1978) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(78)90364-7 · Cited by 181 · see citing works
Self-citation
Effects of aging on visual recognition memory in the rhesus monkey
Moss, M. B., Rosene, D. L., & Peters, A. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80103-9 · Cited by 181 · see citing works
Monoamine neurons in aging and Alzheimer's disease
Palmer, A. M., & DeKosky, S. T. (1993) · Journal of Neural Transmission · doi:10.1007/bf01245229 · Cited by 178 · see citing works
Reversal of spatial memory impairments in aged rats by nerve growth factor and neurotrophins 3 and 4/5 but not by brain-derived neurotrophic factor.
Fischer, W., Sirevaag, A. M., Wiegand, S. J., Lindsay, R. M., & Björklund, A. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.18.8607 · Cited by 170 · see citing works
Memory Deficits in Aged Cebus Monkeys and Facilitation With Central Cholinomimetics
Bartus, R. T., Dean, R. L., & Beer, B. (1980) · Neurobiology of Aging · doi:10.1016/0197-4580(80)90008-1 · Cited by 170 · see citing works
Self-citation
Alzheimer Disease, Attention, and the Cholinergic System
Lawrence, A. D., & Sahakian, B. J. (1995) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199501002-00008 · Cited by 169 · see citing works
Age-related alterations in neurotransmitter receptors: An electrophysiological and biochemical analysis
LIPPA, A. S., Critchett, D. J., Ehlert, F. J., Yamamura, H. I., Enna, S. J., & Bartus, R. T. (1981) · Neurobiology of Aging · doi:10.1016/0197-4580(81)90052-x · Cited by 168 · see citing works
Self-citation
Cognitive Processes of Nonhuman Primates
(1971) · Elsevier eBooks · doi:10.1016/b978-0-12-380850-9.x5001-4 · Cited by 163 · see citing works
Age differences in recognition memory of the rhesus monkey (Macaca mulatta)
Presty, S. K., Bachevalier, J., Walker, L. C., Struble, R. G., Price, D. L., Mishkin, M., & Cork, L. C. (1987) · Neurobiology of Aging · doi:10.1016/0197-4580(87)90038-8 · Cited by 162 · see citing works
Cognitive functions of the basal forebrain cholinergic system in monkeys: memory or attention?
Voytko, M. L. (1996) · Behavioural Brain Research · doi:10.1016/0166-4328(95)00143-3 · Cited by 162 · see citing works
Pain Sensitivity in Schizophrenics
Davis, K. L., Mohs, R. C., & Tinklenberg, J. R. (1979) · New England Journal of Medicine · doi:10.1056/nejm197910253011722 · Cited by 159 · see citing works
Pharmacology of memory: cholinergic—glutamatergic interactions
Aigner, T. G. (1995) · Current Opinion in Neurobiology · doi:10.1016/0959-4388(95)80021-2 · Cited by 157 · see citing works
Monoamine metabolism in senile dementia of Alzheimer type
Cross, A. J., Crow, T. J., Johnson, J. A., Joseph, M. H., Perry, E. K., Perry, R. H., Blessed, G., & Tomlinson, B. E. (1983) · Journal of the Neurological Sciences · doi:10.1016/0022-510x(83)90149-1 · Cited by 150 · see citing works
Recognition memory deficits in a subpopulation of aged monkeys resemble the effects of medial temporal lobe damage
Rapp, P. R., & Amaral, D. G. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90077-w · Cited by 144 · see citing works
Systemic Administration of a Nerve Growth Factor Conjugate Reverses Age-Related Cognitive Dysfunction and Prevents Cholinergic Neuron Atrophy
Bäckman, C. M., Rose, G. M., Hoffer, B. J., Henry, M. A., Bartus, R. T., Friden, P. M., & Granholm, A. (1996) · Journal of Neuroscience · doi:10.1523/jneurosci.16-17-05437.1996 · Cited by 142 · see citing works
Self-citation
Hippocampal neurobiological mechanisms of age-related memory dysfunction
Landfield, P. W. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80116-7 · Cited by 141 · see citing works
Profound effects of combining choline and piracetam on memory enhancement and cholinergic function in aged rats
Bartus, R. T., Dean, R. L., Sherman, K. A., Friedman, E., & Beer, B. (1981) · Neurobiology of Aging · doi:10.1016/0197-4580(81)90007-5 · Cited by 140 · see citing works
Self-citation
Learning impairments following injection of a selective cholinergic immunotoxin, ME20.4 IgG-saporin, into the basal nucleus of Meynert in monkeys
Fine, A., Hoyle, C., Maclean, C. J., LeVatte, T. L., Baker, H. F., & Ridley, R. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00208-x · Cited by 138 · see citing works
Pharmacological Manipulations of the ??2-Noradrenergic System
Coull, J. T. (1994) · Drugs & Aging · doi:10.2165/00002512-199405020-00005 · Cited by 137 · see citing works
Estrogen and Nerve Growth Factor‐related Systems in Brain
Gibbs, R. B. (1994) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1994.tb55792.x · Cited by 128 · see citing works
Decline of Frontal Lobe Functions in Subjects with Age-associated Memory Impairment
Hänninen, T., Hallikainen, M., Koivisto, K. J., Partanen, K. P. L., Laakso, M. P., Riekkinen, P. J., & Soininen, H. S. (1997) · Neurology · doi:10.1212/wnl.48.1.148 · Cited by 126 · see citing works
Strategies for the Development of an Effective Treatment for Senile Dementia
Gever, J. (1982) · Journal of Clinical Psychopharmacology · doi:10.1097/00004714-198206000-00036 · Cited by 126 · see citing works
Effects of aging and dementia upon recent visuospatial memory
Flicker, C., Bartus, R. T., Crook, T. H., & Ferris, S. H. (1984) · Neurobiology of Aging · doi:10.1016/0197-4580(84)90003-4 · Cited by 122 · see citing works
Self-citation
Regulation of Acetylcholine Synthesis: Does Cytoplasmic Acetylcholine Control High Affinity Choline Uptake?
Jenden, D. J., Jope, R. S., & Weiler, M. H. (1976) · Science · doi:10.1126/science.982031 · Cited by 120 · see citing works
Toward Understanding Age-Related Memory Loss in Late Adulthood
Luszcz, M. A., & Bryan, J. (1998) · Gerontology · doi:10.1159/000022048 · Cited by 119 · see citing works
Brain neurotransmitters and receptors in aging and age-related disorders
Enna, S. J., Samorajski, T., & Beer, B. (1981) · Medical Entomology and Zoology · Cited by 118 · see citing works
Loss of place specificity in hippocampal complex spike cells of senescent rat
Barnes, C. A., McNaughton, B. L., & O'Keefe, J. M. (1983) · Neurobiology of Aging · doi:10.1016/0197-4580(83)90034-9 · Cited by 118 · see citing works
Recognition memory span in rhesus monkeys of advanced age
Moss, M. B., Killiany, R., Lai, Z. C., Rosene, D. L., & Herndon, J. G. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(96)00211-4 · Cited by 117 · see citing works
Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.
Shen, J., Barnes, C. A., Wenk, G. L., & McNaughton, B. L. (1996) · Behavioral Neuroscience · doi:10.1037//0735-7044.110.5.1181 · Cited by 116 · see citing works
Long-term functional recovery from age-induced spatial memory impairments by nerve growth factor gene transfer to the rat basal forebrain.
Martı́nez-Serrano, A., Fischer, W., Söderström, S., Ebendal, T., & Björklund, A. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.13.6355 · Cited by 116 · see citing works
The Delayed-Response Problem
Fletcher, H. J. (1965) · Behavior of non-human primates · doi:10.1016/b978-1-4832-2820-4.50011-1 · Cited by 115 · see citing works
Some effects of muscarinic cholinergic blocking drugs on behavior and the electrocorticogram
Meyers, B., Roberts, K. H., Riciputi, R. H., & Domino, E. F. (1964) · Psychopharmacology · doi:10.1007/bf02341261 · Cited by 114 · see citing works
Behavior of Nonhuman Primates: Modern Research Trends
Zimmerman, R. R., Schrier, A. M., & Stollnitz, F. (1972) · The American Journal of Psychology · doi:10.2307/1421725 · Cited by 112 · see citing works
Effects of scopolamine and physostigmine on recognition memory in monkeys with ibotenic-acid lesions of the nucleus basalis of Meynert
Aigner, T. G., Mitchell, S. J., Aggleton, J. P., DeLong, M. R., Struble, R. G., Price, D. L., Wenk, G. L., & Mishkin, M. (1987) · Psychopharmacology · doi:10.1007/bf00210833 · Cited by 112 · see citing works
Reevaluation of the contribution of the basal forebrain cholinergic system to memory
Kesner, R. P. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80122-2 · Cited by 111 · see citing works
Regulation of acetylcholine synthesis in nervous tissue
Haubrich, D. R., & Chippendale, T. J. (1977) · Life Sciences · doi:10.1016/0024-3205(77)90437-4 · Cited by 106 · see citing works
A re-examination of the role of basal forebrain cholinergic neurons in spatial working memory
Chappell, J., McMahan, R., Chiba, A. A., & Gallagher, M. (1998) · Neuropharmacology · doi:10.1016/s0028-3908(98)00032-x · Cited by 106 · see citing works
Anticholinesterase-Induced Amnesia and Its Temporal Aspects
Deutsch, J. A., Hamburg, M. D., & Dahl, H. (1966) · Science · doi:10.1126/science.151.3707.221 · Cited by 105 · see citing works
A Monoclonal Antibody against Acetylcholinesterase Inhibits the Formation of Amyloid Fibrils Induced by the Enzyme
Reyes, A. E., Perez, D. R., Alvarez, A. R., Garrido, J., Gentry, M. K., Doctor, B. P., & Inestrosa, N. C. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6357 · Cited by 104 · see citing works
Pharmacological investigations of the cholinergic imbalance hypotheses of movement disorders and psychosis.
Davis, K. L., & Berger, P. A. (1978) · PubMed · Cited by 101 · see citing works
Changes in Learning and Memory During Aging
Gold, P. E., & McGaugh, J. L. (1975) · Advances in behavioral biology · doi:10.1007/978-1-4684-0925-3_6 · Cited by 101 · see citing works
Hypersensitivity to scopolamine in the elderly
Flicker, C., Ferris, S. H., & Serby, M. (1992) · Psychopharmacology · doi:10.1007/bf02245172 · Cited by 100 · see citing works
Enhancement of Memory by Physostigmine
(1979) · New England Journal of Medicine · doi:10.1056/nejm197910253011721 · Cited by 99 · see citing works
Genetic and environmental aspects of the role of nicotinic receptors in neurodegenerative disorders: Emphasis on Alzheimer's disease and Parkinson's disease
James, J. R., & Nordberg, A. K. (1995) · Behavior Genetics · doi:10.1007/bf02196924 · Cited by 98 · see citing works
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 · see citing works
Differential effects of selective immunotoxic lesions of medial septal cholinergic cells on spatial working and reference memory.
Shen, J., Barnes, C. A., Wenk, G. L., et al. (1996) · Behavioral Neuroscience · doi:10.1037/0735-7044.110.5.1181 · Cited by 95 · see citing works
Apolipoprotein E Genotype and Gender Influence Response to Tacrine Therapya
Farlow, M. R., Lahiri, D. K., Poirier, J., Davignon, J., & Hui, S. L. (1996) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1996.tb32603.x · Cited by 92 · see citing works
Perceptual noise and aging.
Layton, B. S. (1975) · Psychological Bulletin · doi:10.1037/0033-2909.82.6.875 · Cited by 91 · see citing works
Molecular pathology of amyloidogenic proteins and the role of vascular amyloidosis in Alzheimer's disease
Selkoe, D. J. (1989) · Neurobiology of Aging · doi:10.1016/0197-4580(89)90072-9 · Cited by 90 · see citing works
Homovanillic acid and 5-hydroxyindoleacetic acid levels in cerebrospinal fluid of patients with senile dementia of Alzheimer type
Soininen, H. S., MacDonald, E., Rekonen, M., & Riekkinen, P. J. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1981.tb04392.x · Cited by 90 · see citing works
Treatment development strategies for Alzheimer's disease
Crook, T. H. (1986) · Medical Entomology and Zoology · Cited by 88 · see citing works
Possible biochemical basis of memory disorder in Alzheimer disease
Smith, C. M., & Swash, M. (1978) · Annals of Neurology · doi:10.1002/ana.410030602 · Cited by 88 · see citing works
Catecholamines and Cognitive Decline in Aged Nonhuman Primates
Arnsten, A. F. T., & Goldman‐Rakic, P. S. (1985) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1985.tb37592.x · Cited by 88 · see citing works
Effects of oral physostigmine in Alzheimer's disease
Stern, Y., Sano, M. C., & Mayeux, R. P. (1987) · Annals of Neurology · doi:10.1002/ana.410220305 · Cited by 88 · see citing works
Drugs to Treat Age‐Related Neurodegenerative Problems The Final Frontier of Medical Science?
Bartus, R. T. (1990) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1990.tb01430.x · Cited by 87 · see citing works
Self-citation
Long‐term administration of oral physostigmine in Alzheimer's disease
Stern, Y., Sano, M. C., & Mayeux, R. P. (1988) · Neurology · doi:10.1212/wnl.38.12.1837 · Cited by 85 · see citing works
Present Imperfect: A Critical Review of Animal Models of the Mnemonic Impairments in Alzheimer's Disease
McDonald, M. P., & Overmier, J. B. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(97)00024-9 · Cited by 85 · see citing works
Selective removal of cholinergic neurons in the basal forebrain alters cued target detection
Chiba, A. A., Bushnell, P. J., Oshiro, W. M., & Gallagher, M. (1999) · NeuroReport · doi:10.1097/00001756-199909290-00044 · Cited by 83 · see citing works
Restoration of cholinomimetic activity by clonidine in cholinergic plus noradrenergic lesioned rats
Haroutunian, V. H., Kanof, P. D., Tsuboyama, G. K., & Davis, K. L. (1990) · Brain Research · doi:10.1016/0006-8993(90)90280-o · Cited by 83 · see citing works
Basal forebrain—lesioned monkeys are severely impaired in tasks of association and recognition memory
Irle, E., & Markowitsch, H. J. (1987) · Annals of Neurology · doi:10.1002/ana.410220610 · Cited by 82 · see citing works
The ageing brain: normal and abnormal memory
The American Association for Research into Nervous and Mental Diseases, & Albert, M. (1997) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.1997.0152 · Cited by 82 · see citing works
Long-Term Tacrine Treatment in Three Mild Alzheimer Patients
Nordberg, A. K., Amberla, K., Shigeta, M., Lundqvist, H., Viitanen, M. H., Hellström‐Lindahl, E., Johansson, M., Andersson, J., Hartvig, P., Lilja, A., et al. (1998) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199809000-00017 · Cited by 81 · see citing works
An evaluation of drugs for improving memory in aged monkeys: implications for clinical trials in humans.
Bartus, R. T., Dean, R., & Beer, B. (1983) · PubMed · Cited by 77 · see citing works
Self-citation
Different effects on learning ability after injection of the cholinergic immunotoxin ME20.4IgG-saporin into the diagonal band of Broca, basal nucleus of Meynert, or both in monkeys.
Ridley, R. M., Barefoot, H. C., Maclean, C. J., Pugh, P. L., & Baker, H. F. (1999) · Behavioral Neuroscience · doi:10.1037//0735-7044.113.2.303 · Cited by 75 · see citing works
Postsynaptic alpha-2 receptor stimulation improves memory in aged monkeys: Indirect effects of yohimbine versus direct effects of clonidine
Arnsten, A. F. T., & Cai, J. X. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90044-c · Cited by 75 · see citing works
Acute and chronic effects of oral physostigmine and lecithin in Alzheimer's disease
Thal, L. J., Masur, D. M., Sharpless, N. S., Fuld, P. A., & Davies, P. (1986) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(86)90032-1 · Cited by 75 · see citing works
Basal forebrain neurons and memory: A biochemical, histological, and behavioral study of differential vulnerability to ibotenate and quisqualate.
Wenk, G. L., Harrington, C. A., Tucker, D. A., Rance, N. E., & al, E. (1992) · Behavioral Neuroscience · doi:10.1037/0735-7044.106.6.909 · Cited by 69 · see citing works
Neuronal Nicotinic Receptor Deficits in Alzheimer Patients with the Swedish Amyloid Precursor Protein 670/671 Mutation
Marutle, A., Warpman, U., Bogdanović, N., Lannfelt, L., & Nordberg, A. K. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0721161.x · Cited by 66 · see citing works
Memory systems in normal and pathological aging
Rapp, P. R., & Heindel, W. C. (1994) · Current Opinion in Neurology · doi:10.1097/00019052-199408000-00003 · Cited by 66 · see citing works
THE EFFECT OF CHOLINERGIC BLOCKING DRUGS ON SPONTANEOUS ALTERNATION IN RATS.
Meyers, B., & Ef, D. (1964) · PubMed · Cited by 66 · see citing works
Scopolamine challenges in Alzheimer's disease
Sunderland, T., Tariot, P. N., Murphy, D. L., Weingartner, H., Mueller, E. A., & Cohen, R. M. (1985) · Psychopharmacology · doi:10.1007/bf00431817 · Cited by 65 · see citing works
Recent memory in aged non-human primates: Hypersensitivity to visual interference during retention
Bartus, R. T., & Dean, R. L. (1979) · Experimental Aging Research · doi:10.1080/03610737908257214 · Cited by 65 · see citing works
Self-citation
The neurotoxicity of amyloid beta protein in aged primates
McKee, A. C., Kawall, N. W., Schumacher, J. S., & Beal, M. F. (1998) · Amyloid · doi:10.3109/13506129809007283 · Cited by 64 · see citing works
Enhanced Release of Secreted Form of Alzheimer’s Amyloid Precursor Protein from PC12 Cells by Nicotine
Kim, S., Kim, Y. K., Jeong, S., Haass, C., Kim, Y.-H., & Suh, Y. (1997) · Molecular Pharmacology · doi:10.1124/mol.52.3.430 · Cited by 62 · see citing works
Age-related disruption of classical conditioning: A model systems approach to memory disorders
Solomon, P. R., Beal, M. F., & Pendlebury, W. W. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80110-6 · Cited by 57 · see citing works
Animal models of dementia: A synaptic neurochemical perspective
Max, S. R. (1988) · Neurochemistry International · doi:10.1016/0197-0186(88)90044-7 · Cited by 57 · see citing works
Economic considerations in the treatment and management of Alzheimer’s disease
Schumock, G. T. (1998) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/55.suppl_2.s17 · Cited by 56 · see citing works
Neuropeptide effects on memory in aged monkeys
Bartus, R. T., Dean, R. L., & Beer, B. (1982) · Neurobiology of Aging · doi:10.1016/0197-4580(82)90062-8 · Cited by 54 · see citing works
Self-citation
Modulation of Memory by Pituitary Hormones and Related Peptides
Rigter, H., & Crabbe, J. C. (1980) · Vitamins and hormones · doi:10.1016/s0083-6729(08)61070-5 · Cited by 53 · see citing works
Short-term memory in the rhesus monkey: Effects of dopamine blockade via acute haloperidol administration
Bartus, R. T. (1978) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(78)90296-4 · Cited by 53 · see citing works
Self-citation
Acetylcholinesterase inhibitors for Alzheimer's disease
Flicker, L. A. (1999) · BMJ · doi:10.1136/bmj.318.7184.615 · Cited by 49 · see citing works
Cholinergic Markers in Alzheimer Disease
Bartus, R. T., & Emerich, D. F. (1999) · JAMA · doi:10.1001/jama.282.23.2208 · Cited by 49 · see citing works
Self-citation
Behavioral recovery following bilateral lesions of the nucleus basalis does not occur spontaneously
Bartus, R. T., Pontecorvo, M. J., Flicker, C., Dean, R. L., & Figueiredo, J. C. (1986) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(86)90186-3 · Cited by 47 · see citing works
Self-citation
Behavioral Models of Aging in Nonhuman Primates
Dean, R. L., & Bartus, R. T. (1988) · Springer eBooks · doi:10.1007/978-1-4613-0933-8_8 · Cited by 45 · see citing works
Self-citation
Discrimination of Alzheimer patients responding to cholinesterase inhibitor therapy
Alhainen, K., & Riekkinen, P. J. (2009) · Acta Neurologica Scandinavica · doi:10.1111/j.1600-0404.1993.tb04248.x · Cited by 45 · see citing works
Clonidine Treatment of Alzheimer's Disease
Mohr, E., Schlegel, J. R., Fabbrini, G., Williams, J. A., Mouradian, M. M., Mann, U. M., Claus, J. J., Fedio, P., & Chase, T. N. (1989) · Archives of Neurology · doi:10.1001/archneur.1989.00520400030015 · Cited by 45 · see citing works
Improvement in accuracy of delayed recall in aged and non-aged, mature monkeys after intramuscular or transdermal administration of the CNS nicotinic receptor agonist ABT-418
Prendergast, M., Terry, A. V., Jackson, W. J., Marsh, K. C., Decker, M. W., Arnerić, S. P., Buccafusco, J. J., & Terry, A. V. (1997) · Psychopharmacology · doi:10.1007/s002130050240 · Cited by 43 · see citing works
A visual recognition memory test for the assessment of cognitive function in aging and dementia
Flicker, C., Ferris, S. H., Crook, T. H., & Bartus, R. T. (1987) · Experimental Aging Research · doi:10.1080/03610738708259313 · Cited by 43 · see citing works
Self-citation
Monoaminergic and cholinergic synaptic markers in the nucleus basalis of meynert (nbM): Normal age‐related changes and the effect of heart disease and Alzheimer's disease
Sparks, D. L., Hunsaker, J. C., Slevin, J. T., DeKosky, S. T., Kryscio, R. J., & Markesbery, W. R. (1992) · Annals of Neurology · doi:10.1002/ana.410310608 · Cited by 43 · see citing works
Strategies For the development of an Effective Treatment for Senile Dementia
Gershon, C. (1981) · Cited by 43 · see citing works
Cognitive changes during normal aging in monkeys assessed with an automated test apparatus
Voytko, M. L. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90055-g · Cited by 42 · see citing works
Age Changes in Chimpanzees
Riopelle, A. J., & Rogers, C. M. (1965) · Elsevier eBooks · doi:10.1016/b978-1-4832-2821-1.50012-4 · Cited by 42 · see citing works
Guidelines for the evaluation of dementia and age-related cognitive decline.
(1998) · American Psychologist · doi:10.1037/0003-066x.53.12.1298 · Cited by 42 · see citing works
Brain Mechanisms and Intelligence. A Quantitative Study of Injuries to the Brain.
(1930) · Archives of Neurology And Psychiatry · doi:10.1001/archneurpsyc.1930.02220130225023 · Cited by 42 · see citing works
Treatment and Care in Old Age Psychiatry
Levy, R., Howard, R. J., Burns, A. S., & Schneider, L. S. S. (1995) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-199505000-00012 · Cited by 41 · see citing works
Chapter 22 Behavioral and biochemical effects of nucleus basalis magnocellularis lesions: implications and possible relevance to understanding or treating Alzheimer's disease
Bartus, R. T., Flicker, C., Dean, R. L., Fisher, S. K., Pontecorvo, M. J., & Figueiredo, J. C. (1986) · Progress in brain research · doi:10.1016/s0079-6123(08)64315-0 · Cited by 40 · see citing works
Self-citation
Cognitive Function in Normal Aging and Early Dementia
Flicker, C., Ferris, S. H., Crook, T. H., Bartus, R. T., & Reisberg, ‌. (1985) · Advances in applied neurological sciences · doi:10.1007/978-3-642-70644-8_1 · Cited by 39 · see citing works
Self-citation
Cannabinoids And The Cholinergic System
Domino, E. F. (1981) · The Journal of Clinical Pharmacology · doi:10.1002/j.1552-4604.1981.tb02602.x · Cited by 39 · see citing works
Age-related memory deficits in Swiss mice
Kubanis, P., Gobbel, G. T., & Zornetzer, S. F. (1981) · Behavioral and Neural Biology · doi:10.1016/s0163-1047(81)90555-0 · Cited by 39 · see citing works
Behavioral changes in aged rhesus monkeys
Bachevalier, J. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90048-g · Cited by 39 · see citing works
Cholinergic drug effects on memory and cognition in animals.
Bartus, R. T. (1980) · American Psychological Association eBooks · doi:10.1037/10050-011 · Cited by 37 · see citing works
Self-citation
Nutrition in Gerontology
(1984) · Journal of Gerontology · doi:10.1093/geronj/39.6.760 · Cited by 36 · see citing works
Four Stimulants of the Central Nervous System: Effects on Short-Term Memory in Young versus Aged Monkeys*
Bartus, R. T. (1979) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1979.tb06042.x · Cited by 36 · see citing works
Self-citation
Neuropsychological analysis of learning and memory in the aged nonhuman primate
Rapp, P. R. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90050-l · Cited by 36 · see citing works
Age Differences in Retention of Concurrent Discrimination Problems in Monkeys
Medin, D. L., O'Neil, P., Smeltz, E., & Davis, R. T. (1973) · Journal of Gerontology · doi:10.1093/geronj/28.1.63 · Cited by 36 · see citing works
Emerging drugs for Alzheimer's disease. Mechanisms of action and prospects for cognitive enhancing medications.
Schneider, L. S., & Tariot, P. (1994) · The Medical clinics of North America · doi:10.1016/s0025-7125(16)30142-0 · Cited by 31 · see citing works
The need for common perspectives in the development and use of animal models for age-related cognitive and neurodegenerative disorders
Bartus, R. T. (1988) · Neurobiology of Aging · doi:10.1016/s0197-4580(88)80097-6 · Cited by 31 · see citing works
Self-citation
Age differences in short-term memory of test-sophisticated rhesus monkeys
Marriott, J. G., & Abelson, J. S. (1980) · AGE · doi:10.1007/bf02434999 · Cited by 30 · see citing works
Effects of Cholinergic Enhancement Therapies on Memory Function in Alzheimer's Disease: A Meta-Analysis of the Literature
Jorm, A. F. (1986) · Australian & New Zealand Journal of Psychiatry · doi:10.3109/00048678609161337 · Cited by 30 · see citing works
Guanfacine Treatment of Alzheimerʼs Disease
Schlegel, J. R., Mohr, E., Williams, J. A., Mann, U. M., Gearing, M., & Chase, T. N. (1989) · Clinical Neuropharmacology · doi:10.1097/00002826-198904000-00007 · Cited by 29 · see citing works
Cholinergic-glutamatergic interactions in visual recognition memory of rhesus monkeys
Matsuoka, N., & Aigner, T. G. (1996) · Neuroreport · doi:10.1097/00001756-199601310-00045 · Cited by 29 · see citing works

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Alzheimer's disease: Targeting the Cholinergic System
H. Ferreira-Vieira, T., M. Guimaraes, I., R. Silva, F., & M. Ribeiro, F. (2016) · Current Neuropharmacology · doi:10.2174/1570159x13666150716165726 · Cited by 1,551 · see citing works
The Cholinergic Hypothesis of Age and Alzheimer’s Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development
Terry, A. V., & Buccafusco, J. J. (2003) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.102.041616 · Cited by 1,159 · see citing works
The cholinergic system in aging and neuronal degeneration
Schliebs, R., & Arendt, T. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.058 · Cited by 1,047 · see citing works
Aging cognition: from neuromodulation to representation
Li, S., Lindenberger, U., & Sikström, S. (2001) · Trends in Cognitive Sciences · doi:10.1016/s1364-6613(00)01769-1 · Cited by 884 · see citing works
The Brain Metabolite Kynurenic Acid Inhibits α7 Nicotinic Receptor Activity and Increases Non-α7 Nicotinic Receptor Expression: Physiopathological Implications
Hilmas, C., Pereira, E., Alkondon, M., Rassoulpour, A., Schwarcz, R., & Albuquerque, E. X. (2001) · Journal of Neuroscience · doi:10.1523/jneurosci.21-19-07463.2001 · Cited by 772 · see citing works
Modes and models of forebrain cholinergic neuromodulation of cognition
Hasselmo, M. E., & Sarter, M. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.104 · Cited by 733 · see citing works
Impact of aging on hippocampal function: plasticity, network dynamics, and cognition
Rosenzweig, E. S., & Barnes, C. A. (2003) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00126-0 · Cited by 730 · see citing works
Upregulation of choline acetyltransferase activity in hippocampus and frontal cortex of elderly subjects with mild cognitive impairment
DeKosky, S. T., Ikonomovic, M. D., Styren, S. D., Beckett, L., Wisniewski, S., Bennett, D. A., Cochran, E. J., Kordower, J. H., & Mufson, E. J. (2002) · Annals of Neurology · doi:10.1002/ana.10069 · Cited by 686 · see citing works
The pharmacology, neuroanatomy and neurogenetics of one-trial object recognition in rodents
Dere, E., Huston, J. P., & Silva, M. A. D. S. (2007) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.01.005 · Cited by 669 · see citing works
Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies
Auld, D. S., Kornecook, T. J., Bastianetto, S., & Quirion, R. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00079-5 · Cited by 669 · see citing works
Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development
Wess, J., Eglen, R. M., & Gautam, D. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2379 · Cited by 637 · see citing works
Cholinergic system during the progression of Alzheimer’s disease: therapeutic implications
Mufson, E. J., Counts, S., Perez, S. E., & Ginsberg, S. D. (2008) · Expert Review of Neurotherapeutics · doi:10.1586/14737175.8.11.1703 · Cited by 589 · see citing works
The significance of the cholinergic system in the brain during aging and in Alzheimer’s disease
Schliebs, R., & Arendt, T. (2006) · Journal of Neural Transmission · doi:10.1007/s00702-006-0579-2 · Cited by 531 · see citing works
Revisiting the cholinergic hypothesis in the development of Alzheimer's disease
Craig, L. A., Hong, N. S., & McDonald, R. J. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.03.001 · Cited by 487 · see citing works
Cholinergic modulation of the hippocampal region and memory function
Haam, J., & Yakel, J. L. (2017) · Journal of Neurochemistry · doi:10.1111/jnc.14052 · Cited by 446 · see citing works
Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease
Daulatzai, M. A. (2016) · Journal of Neuroscience Research · doi:10.1002/jnr.23777 · Cited by 433 · see citing works
Noradrenergic mechanisms in neurodegenerative diseases: a theory
Marien, M. R., Colpaert, F. C., & Rosenquist, A. C. (2004) · Brain Research Reviews · doi:10.1016/j.brainresrev.2004.02.002 · Cited by 411 · see citing works
Naturally Occurring Acetylcholinesterase Inhibitors and Their Potential Use for Alzheimer's Disease Therapy
dos Santos, T. C., Gomes, T. M., Pinto, B., Camara, A. L., & Paes, A. M. D. A. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01192 · Cited by 393 · see citing works
Pharmacology and Therapeutic Potential of Sigma1 Receptor Ligands
Cobos, E., Entrena, J., Nieto, F., Cendán, C., & del Pozo, E. (2008) · Current Neuropharmacology · doi:10.2174/157015908787386113 · Cited by 373 · see citing works
The history of the cholinergic hypothesis
Contestabile, A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2009.12.044 · Cited by 373 · see citing works
Recent progress in the identification of selective butyrylcholinesterase inhibitors for Alzheimer's disease
Li, Q., Yang, H., Chen, Y., & Sun, H. (2017) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2017.03.062 · Cited by 331 · see citing works
Metabolic imprinting of choline by its availability during gestation: implications for memory and attentional processing across the lifespan
Meck, W. H., & Williams, C. L. (2003) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(03)00069-1 · Cited by 325 · see citing works
Muscarinic receptor subtypes in neuronal and non‐neuronal cholinergic function
Eglen, R. M. (2006) · Autonomic and Autacoid Pharmacology · doi:10.1111/j.1474-8673.2006.00368.x · Cited by 311 · see citing works
Enrichment enhances spatial memory and increases synaptophysin levels in aged female mice
Frick, K. M., & Fernandez, S. M. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00138-0 · Cited by 303 · see citing works
Mechanistic insights and perspectives involved in neuroprotective action of quercetin
Grewal, A. K., Singh, T. G., Sharma, D., Sharma, V., Singh, M., Rahman, M. H., Najda, A., Walasek-Janusz, M., Kamel, M. S., Albadrani, G. M., et al. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111729 · Cited by 287 · see citing works
Atrophy of the Cholinergic Basal Forebrain Over the Adult Age Range and in Early Stages of Alzheimer's Disease
Grothe, M. J., Heinsen, H., & Teipel, S. J. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.06.019 · Cited by 283 · see citing works
Attentional functions of cortical cholinergic inputs: What does it mean for learning and memory?
Sarter, M. F., Bruno, J. P., & Givens, B. S. (2003) · Neurobiology of Learning and Memory · doi:10.1016/s1074-7427(03)00070-4 · Cited by 278 · see citing works
Motor cortex hyperexcitability to transcranial magnetic stimulation in Alzheimer's disease
Lazzaro, V. D. (2004) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.2003.018127 · Cited by 274 · see citing works
Operational calixarene-based fluorescent sensing systems for choline and acetylcholine and their application to enzymatic reactions
Guo, D., Uzunova, V. D., Su, X., Liu, Y., & Nau, W. M. (2011) · Chemical Science · doi:10.1039/c1sc00231g · Cited by 257 · see citing works
β-Amyloid Peptide Activates α7 Nicotinic Acetylcholine Receptors Expressed in Xenopus Oocytes
Dineley, K. T., Bell, K. A., Bui, D., & Sweatt, J. D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200066200 · Cited by 241 · see citing works
Neuroprotective Effects of Marine Algae
Pangestuti, R., & Kim, S. (2011) · Marine Drugs · doi:10.3390/md9050803 · Cited by 245 · see citing works
A Selective Allosteric Potentiator of the M 1 Muscarinic Acetylcholine Receptor Increases Activity of Medial Prefrontal Cortical Neurons and Restores Impairments in Reversal Learning
Shirey-Rice, J. K., Brady, A. E., Jones, P. J., Davis, A. A., Bridges, T. M., Kennedy, J. P., Jadhav, S. B., Menon, U. N., Xiang, Z., Watson, M. L., et al. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.3930-09.2009 · Cited by 237 · see citing works
Therapeutic Opportunities for Muscarinic Receptors in the Central Nervous System
Felder, C. C., Bymaster, F. P., Ward, J. S., & DeLapp, N. W. (2000) · Journal of Medicinal Chemistry · doi:10.1021/jm990607u · Cited by 235 · see citing works
Chronic Caffeine Consumption Prevents Memory Disturbance in Different Animal Models of Memory Decline
Cunha, R. A., & Agostinho, P. M. (2010) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-1408 · Cited by 233 · see citing works
Modeling behavioral and neuronal symptoms of Alzheimer's disease in mice: A role for intraneuronal amyloid
Giménez‐Llort, L., Blázquez, G., Cañete, T., Johansson, B. A., Oddo, S., Tobeña, A., LaFerla, F. M., & Fernández‐Teruel, A. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2006.07.007 · Cited by 232 · see citing works
Rivastigmine: the advantages of dual inhibition of acetylcholinesterase and butyrylcholinesterase and its role in subcortical vascular dementia and Parkinson’s disease dementia
Kandiah, N., Pai, M.-C., Senanarong, V., Looi, I., Ampil, E. R., Park, K. W., Karanam, A. K., & Christopher, S. (2017) · Clinical Interventions in Aging · doi:10.2147/cia.s129145 · Cited by 232 · see citing works
Rational Approach To Discover Multipotent Anti-Alzheimer Drugs
Rosini, M., Andrisano, V., Bartolini, M., Bolognesi, M. L., Hrelia, P., Minarini, A., Tarozzi, A., & Melchiorre, C. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049112h · Cited by 228 · see citing works
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 · see citing works
Self-citation
Cholinergic Neurotransmission Is Essential for Perirhinal Cortical Plasticity and Recognition Memory
Warburton, E. C., Koder, T., Cho, K., Massey, P. V., Duguid, G., Barker, G. R. I., Aggleton, J. P., Bashir, Z. I., & Brown, M. W. (2003) · Neuron · doi:10.1016/s0896-6273(03)00358-1 · Cited by 226 · see citing works
The Role of Nerve Growth Factor Receptors in Cholinergic Basal Forebrain Degeneration in Prodromal Alzheimer Disease
Counts, S., & Mufson, E. J. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.4.263 · Cited by 223 · see citing works
Vascular determinants of cholinergic deficits in Alzheimer disease and vascular dementia.
Román, G. C., & Kalaria, R. N. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.10.004 · Cited by 213 · see citing works
Nerve growth factor and galantamine ameliorate early signs of neurodegeneration in anti-nerve growth factor mice
Capsoni, S., Giannotta, S., & Cattaneo, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.192442999 · Cited by 213 · see citing works
Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease
Li, Q., He, S., Chen, Y., Feng, F., Qu, W., & Sun, H. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.09.031 · Cited by 211 · see citing works
Estrogen therapy and cognition: a review of the cholinergic hypothesis
Gibbs, R. B. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0036 · Cited by 206 · see citing works
Histamine receptors in the CNS as targets for therapeutic intervention
Passani, M. B., & Blandina, P. (2011) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2011.01.003 · Cited by 206 · see citing works
Interactions of AChE with A? Aggregates in Alzheimer?s Brain: Therapeutic Relevance of IDN 5706
Carvajal, F. J., & Inestrosa, N. C. (2011) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2011.00019 · Cited by 204 · see citing works
Discovery of Histamine H3 Antagonists for the Treatment of Cognitive Disorders and Alzheimer’s Disease
Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R., & Cowart, M. (2010) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.110.166876 · Cited by 329 · see citing works
Long-term continuous, but not daily, environmental enrichment reduces spatial memory decline in aged male mice
BENNETT, J., McRae, P. A., Levy, L. J., & Frick, K. M. (2005) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2005.09.003 · Cited by 198 · see citing works
Effects of lavender oil inhalation on improving scopolamine-induced spatial memory impairment in laboratory rats
Hriţcu, L., Cioancă, O., & Hăncianu, M. (2012) · Phytomedicine · doi:10.1016/j.phymed.2012.02.002 · Cited by 197 · see citing works
Septohippocampal Acetylcholine: Involved in but not Necessary for Learning and Memory?Preprint
Parent, M. B., & Baxter, M. G. (2004) · Learning & Memory · doi:10.1101/lm.69104 · Cited by 194 · see citing works
Effects of the cognition impairer MK-801 on learning and memory in mice and rats
van der Staay, F. J., Rutten, K., Erb, C., & Blokland, A. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.01.052 · Cited by 192 · see citing works
Foreign language training as cognitive therapy for age-related cognitive decline: A hypothesis for future research
Antoniou, M., Gunasekera, G. M., & Wong, P. C. M. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.09.004 · Cited by 198 · see citing works
Mechanisms of Melatonin in Alleviating Alzheimer’s Disease
Shukla, M., Govitrapong, P., Boontem, P., Reiter, R., & Satayavivad, J. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170313123454 · Cited by 173 · see citing works
Cholinergic receptor pathways involved in apoptosis, cell proliferation and neuronal differentiation
Resende, R. R., & Adhikari, A. (2009) · Cell Communication and Signaling · doi:10.1186/1478-811x-7-20 · Cited by 190 · see citing works
Wnt Signaling: Role in Alzheimer Disease and Schizophrenia
Inestrosa, N. C., Montecinos-Oliva, C., & Fuenzalida, M. (2012) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-012-9417-5 · Cited by 186 · see citing works
Broad-Spectrum Efficacy across Cognitive Domains by α7 Nicotinic Acetylcholine Receptor Agonism Correlates with Activation of ERK1/2 and CREB Phosphorylation Pathways
Bitner, R. S., Bunnelle, W. H., Anderson, D. J., Briggs, C. A., Buccafusco, J. J., Curzon, P., Decker, M. W., Frost, J. M., Grønlien, J. H., Gubbins, E. J., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.2444-07.2007 · Cited by 184 · see citing works
Cerebral cortex : principles of operation
Rolls, E. T. (2016) · doi:10.82444/warw.33712699 · Cited by 187 · see citing works
Reduction of cortical TrkA but not p75NTR protein in early‐stage Alzheimer's disease
Counts, S., Nadeem, M., Wuu, J., Ginsberg, S. D., Saragovi, H. U., & Mufson, E. J. (2004) · Annals of Neurology · doi:10.1002/ana.20233 · Cited by 183 · see citing works
Long-term Effects of Cholinesterase Inhibitors on Cognitive Decline and Mortality
Xu, H., Garcia-Ptacek, S., Jönsson, L., Wimo, A., Nordström, P., & Eriksdotter, M. (2021) · Neurology · doi:10.1212/wnl.0000000000011832 · Cited by 182 · see citing works
Longitudinal measures of cholinergic forebrain atrophy in the transition from healthy aging to Alzheimer's disease
Grothe, M. J., Heinsen, H., & Teipel, S. J. (2012) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.10.018 · Cited by 179 · see citing works
Cholinergic modulation of cognition: Insights from human pharmacological functional neuroimaging
Bentley, P., Driver, J., & Dolan, R. J. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.06.002 · Cited by 173 · see citing works
Bioactivity of AAV2‐neurturin gene therapy (CERE‐120): Differences between Parkinson's disease and nonhuman primate brains
Bartus, R. T., Herzog, C. D., Chu, Y., Wilson, A., Brown, L., Siffert, J. O., Johnson, E. M., Olanow, C. W., Mufson, E. J., & Kordower, J. H. (2010) · Movement Disorders · doi:10.1002/mds.23442 · Cited by 170 · see citing works
Self-citation
Mouse models of Down syndrome as a tool to unravel the causes of mental disabilities
Rueda, N., Flórez, J., & Martínez-Cué, C. (2012) · Neural Plasticity · doi:10.1155/2012/584071 · Cited by 171 · see citing works
Cognitive Aging in Zebrafish
Yu, L., Tucci, V., Kishi, S., & Zhdanova, I. V. (2006) · PLoS ONE · doi:10.1371/journal.pone.0000014 · Cited by 170 · see citing works
Cholinergic modulation of a specific memory function of prefrontal cortex
Croxson, P. L., Kyriazis, D. A., & Baxter, M. G. (2011) · Nature Neuroscience · doi:10.1038/nn.2971 · Cited by 166 · see citing works
The Magic of Crystal Structure-Based Inhibitor Optimization: Development of a Butyrylcholinesterase Inhibitor with Picomolar Affinity and in Vivo Activity
Košak, U., Brus, B., Knez, D., Žakelj, S., Trontelj, J., Pišlar, A. H., Šink, R., Jukič, M., Živin, M., Podkowa, A., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01086 · Cited by 166 · see citing works
Central Nicotinic Receptors: Structure, Function, Ligands, and Therapeutic Potential
Romanelli, M. N., Gratteri, P., Guandalini, L., Martini, E., Bonaccini, C., & Gualtieri, F. (2007) · ChemMedChem · doi:10.1002/cmdc.200600207 · Cited by 164 · see citing works
AR-R 17779 improves social recognition in rats by activation of nicotinic α7 receptors
van Kampen, M., Selbach, K., Schneider, R., Schiegel, E., Boess, F., & Schreiber, R. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1668-7 · Cited by 160 · see citing works
Innovative Therapy for Alzheimer’s Disease-With Focus on Biodelivery of NGF
Mitra, S., Behbahani, H., & Eriksdotter, M. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00038 · Cited by 159 · see citing works
Encapsulated Cell Biodelivery of Nerve Growth Factor to the Basal Forebrain in Patients with Alzheimer’s Disease
Eriksdotter, M., Linderoth, B., Lind, G., Aladellie, L., Almkvist, O., Andreasen, N., Blennow, K., Bogdanović, N., Jelić, V., Kadir, A., et al. (2012) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000336051 · Cited by 158 · see citing works
Cholinergic Treatments with Emphasis on M1 Muscarinic Agonists as Potential Disease-Modifying Agents for Alzheimer's Disease
Fisher, A. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.002 · Cited by 151 · see citing works
Design, Synthesis, and Biological Evaluation of Conformationally Restricted Rivastigmine Analogues
Bolognesi, M. L., Bartolini, M., Cavalli, A., Andrisano, V., Rosini, M., Minarini, A., & Melchiorre, C. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049782n · Cited by 150 · see citing works
Developmental origins of the age-related decline in cortical cholinergic function and associated cognitive abilities
Sarter, M. F., & Bruno, J. P. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.11.011 · Cited by 148 · see citing works
M1 muscarinic acetylcholine receptor in Alzheimer’s disease
Jiang, S., Li, Y., Zhang, C., Zhao, Y., Bu, G., Xu, H., & Zhang, Y. (2014) · Neuroscience Bulletin · doi:10.1007/s12264-013-1406-z · Cited by 147 · see citing works
Target Identification for CNS Diseases by Transcriptional Profiling
Altar, C. A., Vawter, M. P., & Ginsberg, S. D. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.172 · Cited by 139 · see citing works
Cholinergic modulation of amyloid precursor protein processing with emphasis on M1 muscarinic receptor: perspectives and challenges in treatment of Alzheimer’s disease
Fisher, A. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07507.x · Cited by 140 · see citing works
Triazole derivatives as inhibitors of Alzheimer's disease: Current developments and structure-activity relationships
Xu, M., Peng, Y., Zhu, L., Wang, S., Ji, J., & Rakesh, K. P. (2019) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2019.07.059 · Cited by 141 · see citing works
Further evidence for the cholinergic hypothesis of aging and dementia from the canine model of aging
Araujo, J. A., Studzinski, C. M., & Milgram, N. W. (2005) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.12.008 · Cited by 140 · see citing works
Nobiletin, a Citrus Flavonoid That Improves Memory Impairment, Rescues Bulbectomy-Induced Cholinergic Neurodegeneration in Mice
Nakajima, A., Yamakuni, T., Haraguchi, M., Omae, N., Song, S.-Y., Kato, C., Nakagawasai, O., Tadano, T., Yokosuka, A., Mimaki, Y., et al. (2007) · Journal of Pharmacological Sciences · doi:10.1254/jphs.sc0070155 · Cited by 137 · see citing works
Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer’s disease patients: application of a second-generation encapsulated cell biodelivery device
Eyjolfsdottir, H., Eriksdotter, M., Linderoth, B., Lind, G., Juliusson, B., Kusk, P., Almkvist, O., Andreasen, N., Blennow, K., Ferreira, D., et al. (2016) · Alzheimer s Research & Therapy · doi:10.1186/s13195-016-0195-9 · Cited by 137 · see citing works
Propidium-Based Polyamine Ligands as Potent Inhibitors of Acetylcholinesterase and Acetylcholinesterase-Induced Amyloid-β Aggregation
Bolognesi, M. L., Andrisano, V., Bartolini, M., Banzi, R., & Melchiorre, C. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm049156q · Cited by 136 · see citing works
Nerve growth factor metabolic dysfunction in Alzheimer's disease and Down syndrome
Iulita, M. F., & Cuello, A. C. (2014) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2014.04.010 · Cited by 135 · see citing works
Cholinergic dysfunction, neuronal damage and axonal loss in TgCRND8 mice
Bellucci, A., Luccarini, I., Scali, C., Prosperi, C., Giovannini, M. G., Pepeu, G., & Casamenti, F. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.03.012 · Cited by 130 · see citing works
Symptomatic effect of donepezil, rivastigmine, galantamine and memantine on cognitive deficits in the APP23 model
Dam, D. V., Abramowski, D., Staufenbiel, M., & Deyn, P. P. D. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2132-z · Cited by 130 · see citing works
Lecozotan (SRA-333): A Selective Serotonin 1A Receptor Antagonist That Enhances the Stimulated Release of Glutamate and Acetylcholine in the Hippocampus and Possesses Cognitive-Enhancing Properties
Schechter, L. E., Smith, D. L., Rosenzweig-Lipson, S. J., Rizzo, S. J. S., Dawson, L. A., Marquis, K. L., Jones, D. P., Piesla, M. J., Andree, T. H., Nawoschik, S. P., et al. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.086363 · Cited by 129 · see citing works
Gonadal Steroids, Learning, and Memory
Dohanich, G. P. (2002) · Elsevier eBooks · doi:10.1016/b978-012532104-4/50024-x · Cited by 130 · see citing works
Cholinergic Activity Enhances Hippocampal Long-Term Potentiation in CA1 during Walking in Rats
Leung, L.-W. S., Bixia Shen, A., Rajakumar, N., & Ma, J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-28-09297.2003 · Cited by 129 · see citing works
Targeted Deletion of the Kynurenine Aminotransferase II Gene Reveals a Critical Role of Endogenous Kynurenic Acid in the Regulation of Synaptic Transmission viaα7 Nicotinic Receptors in the Hippocampus
Alkondon, M., Pereira, E. F. R., Yü, P., Arruda, E. Z., Almeida, L. E. F., Guidetti, P., Fawcett, W. P., Sapko, M. T., Randall, W. R., Schwarcz, R. M., et al. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5631-03.2004 · Cited by 129 · see citing works
The apolipoprotein E gene, attention, and brain function.
Parasuraman, R., Greenwood, P. M., & Sunderland, T. (2002) · Neuropsychology · doi:10.1037//0894-4105.16.2.254 · Cited by 127 · see citing works
and Alzheimer's disease
Brioni, J. D., Esbenshade, T. A., Garrison, T. R., Bitner, S. R., & Cowart, M. (2010) · Cited by 125 · see citing works
Alzheimer’s disease due to loss of function: A new synthesis of the available data
Kepp, K. P. (2016) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2016.06.004 · Cited by 123 · see citing works
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 · see citing works
Challenging the cholinergic system in mild cognitive impairment: a pharmacological fMRI study
Goekoop, R., Rombouts, S. A. R. B., Jonker, C., Hibbel, A., Knol, D. L., Truyen, L., Barkhof, F., & Scheltens, P. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.08.006 · Cited by 122 · see citing works
Cholinergic system function and cognition in mild cognitive impairment
Haense, C., Kalbe, E., Herholz, K., Hohmann, C., Neumaier, B., Krais, R., & Heiss, W. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.08.015 · Cited by 121 · see citing works
Combined Blockade of Cholinergic Receptors Shifts the Brain from Stimulus Encoding to Memory Consolidation
Rasch, B. H., Born, J., & Gais, S. (2006) · Journal of Cognitive Neuroscience · doi:10.1162/jocn.2006.18.5.793 · Cited by 137 · see citing works
Muscarinic Receptor Activation Protects Cells from Apoptotic Effects of DNA Damage, Oxidative Stress, and Mitochondrial Inhibition
Sarno, P. D., Shestopal, S. A., King, T. D., Zmijewska, A. A., Song, L., & Jope, R. S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212157200 · Cited by 119 · see citing works
Light-Induced Pupillary Responses in Alzheimer's Disease
Chougule, P. S., Najjar, R. P., Finkelstein, M. T., Kandiah, N., & Miléa, D. (2019) · Frontiers in Neurology · doi:10.3389/fneur.2019.00360 · Cited by 117 · see citing works
Cholinergic challenge in Alzheimer patients and mild cognitive impairment differentially affects hippocampal activation—a pharmacological fMRI study
Goekoop, R., Scheltens, P., Barkhof, F., & Rombouts, S. A. R. B. (2005) · Brain · doi:10.1093/brain/awh671 · Cited by 116 · see citing works
Comparison of ginsenosides Rg1 and Rb1 for their effects on improving scopolamine‐induced learning and memory impairment in mice
Wang, Q., Sun, L., Jia, W. W.-G., Liu, X., Dang, H., Mai, W., Wang, N., Steinmetz, A. A., Yu-qin, W., & Xu, C. (2010) · Phytotherapy Research · doi:10.1002/ptr.3130 · Cited by 115 · see citing works
Alpha7 nicotinic receptor up-regulation in cholinergic basal forebrain neurons in Alzheimer disease.
Counts, S., He, B., Che, S.-L., Ikonomovic, M., DeKosky, S., Ginsberg, S. D., & Mufson, E. (2007) · Archives of Neurology · doi:10.1001/archneur.64.12.1771 · Cited by 115 · see citing works

Effect of tetrahydrocannabinols on brain acetylcholine
Askew, W. E., Kimball, A. P., & Ho, B. T. (1974) · Brain Research · doi:10.1016/0006-8993(74)90018-3 · Cited by 28 · see citing works
Twenty years of cholinergic intervention in Alzheimer's disease: A tale of disappointment and ultimate confidence
Rainer, M. K., & Mucke, H. A. (1998) · International Journal of Psychiatry in Clinical Practice · doi:10.3109/13651509809115353 · Cited by 4 · see citing works
The cholinergic pathology in Alzheimer's disease - discrepancies between clinical experience and pathophysiological findings
Frölich, L. (2002) · Journal of Neural Transmission · doi:10.1007/s007020200083 · Cited by 94 · see citing works
A second wind for the cholinergic system in Alzheimer’s therapy
Douchamps, V., & Mathis, C. (2017) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000300 · Cited by 58 · see citing works
Pharmacological drug treatment of Alzheimer disease: The cholinergic hypothesis revisited
Ladner, C. J., & Lee, J. M. (1998) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199808000-00001 · Cited by 142 · see citing works

Authors: Bartus, R. T.
Affiliations: Alkermes (United States) (US)
Corresponding author: Bartus, Raymond T.
Venue: Experimental Neurology
Publisher: Elsevier BV
Published: 2000-06
Volume: 163
Issue: 2
Pages: 495-529
ISSN: 0014-4886 (ISSN-L)
DOI: 10.1006/exnr.2000.7397
OpenAlex: W2026745182
Cited by: 829
References: 231
Citations by year: 2026: 15 · 2025: 23 · 2024: 19 · 2023: 21 · 2022: 42 · 2021: 34 · 2020: 26 · 2019: 22 · 2018: 32 · 2017: 38 · 2016: 34 · 2015: 24 · 2014: 30 · 2013: 40 · 2012: 38
FWCI: 3.59
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Experimental Neurology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: cholinergic hypothesis, Alzheimer's disease, neurodegenerative diseases, animal models of disease, Alzheimer's disease treatment, palliative care, cholinesterase inhibitors
MeSH terms: Age Factors, Alzheimer Disease, Animals, Cognition, Disease Models, Animal, Forecasting, Humans, Memory Disorders, Cholinergic Agents

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On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis

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