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Central Anticholinergic Hypersensitivity in Aging
Abstract
Although neurochemical reductions in cholinergic systems have been found to occur during aging, such changes do not necessarily translate to functional deficits. The cognitive deficits of normal aging have been attributed in part to hypo-cholinergic function, but anticholinergic hypersensitivity in the elderly has not been systematically documented. To test the cholinergic hypothesis of aging, we investigated the effects of scopolamine on memory and attention in healthy young and elderly subjects. Treatments included intramuscular glycopyrrolate (0.0044 mg/kg) and scopolamine (0.002, 0.004, and 0.007 mg/kg) in a randomized double-blind design. The test battery included the Selective Reminding Task (SRT), Digit Span, Paired Associates Learning (PAL), Symbol Digit Modalities Test (SDMT), and the Continuous Performance Task. Elderly controls were more impaired at lower scopolamine doses than were the young on SRT, PAL, and SDMT. These results demonstrate anticholinergic hypersensitivity and are consistent with decremental changes in cholinergic status during normal aging. ( J Geriatr Psychiatry Neurol 1992;5:72–77).
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“A well-known risk with anticholinergic medications is acute impairment in specific aspects of cognition (e.g., working memory, attention, psychomotor speed) which has been demonstrated in single dose experimental studies 9-12 and cohort studies.13”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [9]
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Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study
Gray, S. L., Anderson, M. L., Dublin, S., Hanlon, J. T., Hubbard, R., Walker, R., Yu, O., Crane, P. K., & Larson, E. B. (2015) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2014.7663 · Cited by 1,111
Drug-Induced Cognition Disorders in the Elderly: Incidence, Prevention and Management
Gray, S. L., Lai, K. V., & Larson, E. B. (1999) · Drug Safety · doi:10.2165/00002018-199921020-00004 · Cited by 190
Anticholinergics: theoretical and clinical overview
Nishtala, P. S., Salahudeen, M. S., & Hilmer, S. N. (2016) · Expert Opinion on Drug Safety · doi:10.1517/14740338.2016.1165664 · Cited by 167
Anticholinergic Drug Burden in Older People's Brain - How well is it Measured?
Kersten, H., & Wyller, T. B. (2014) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.12140 · Cited by 112
Cholinergic modulation of preattentive auditory processing in aging
Pekkonen, E., Jääskeläinen, I. P., Kaakkola, S., & Ahveninen, J. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.04.018 · Cited by 73
Metadata
- Authors
- Ray, P. G., Meador, K. J., Loring, D. W., Zamrini, E. W., Yang, X.-H., & Buccafusco, J. J.
- Affiliations
- Augusta University (US)
- Venue
- Journal of Geriatric Psychiatry and Neurology
- Publisher
- SAGE Publications
- Published
- 1992-04
- Volume
- 5
- Issue
- 2
- Pages
- 72-77
- ISSN
- 0891-9887 (ISSN-L)
- 1552-5708
- OpenAlex
- W1992268087
- Cited by
- 75
- References
- 1
- Citations by year
- 2026: 1 · 2023: 1 · 2020: 4 · 2019: 3 · 2018: 3 · 2017: 3 · 2016: 4 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 1.82
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Geriatric Psychiatry and Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute on Aging (AG00314)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Geriatrics and Gerontology › Pharmaceutical Practices and Patient Outcomes
- Keywords
- normal aging, scopolamine, glycopyrrolate, memory, attention, cognitive impairment, paired-associate learning, Symbol Digit Modalities Test, continuous performance test, digit span
- MeSH terms
- Adult, Aged, Aging, Arousal, Cerebral Cortex, Dose-Response Relationship, Drug, Double-Blind Method, Female, Glycopyrrolate, Humans, Male, Middle Aged, Synaptic Transmission, Neuropsychological Tests, Mental Recall, Receptors, Cholinergic, Scopolamine
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