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Increased Alzheimer pathology in Parkinson's disease related to antimuscarinic drugs
Open accessAbstract
The hypothesis that blockade of muscarinic receptors is associated with increased Alzheimer‐type pathology was investigated in Parkinson's disease. Amyloid plaque densities were more than 2.5‐fold higher in cases treated with antimuscarinic medication in the long term compared with untreated or short‐term treated cases ( p = 0.005 and 0.00005, respectively). Neurofibrillary tangle densities were also highest in chronic compared with untreated or acute‐treated groups ( p = 0.02 and 0.05, respectively). The findings, if replicated, have potential implications for the use of anticholinergic medication in elderly Parkinson's disease patients. Ann Neurol 2003
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Mechanistic evidence for a link between anticholinergic drugs and dementia incidence is limited, but neuropathological studies in humans and mice do support a role of anticholinergics affecting neurodegenerative pathology.
“Mechanistic evidence for a link between anticholinergic drugs and dementia incidence is limited, but neuropathological studies in humans and mice do support a role of anticholinergics affecting neurodegenerative pathology.37 38”
From Anticholinergic drugs and risk of dementia: case-control study (2018) · cites this paper as [38]
One biologically plausible mechanism for these findings is that cumulative use of these agents results in abnormal brain pathology similar to that observed with Alzheimer's Disease (AD).
“One biologically plausible mechanism for these findings is that cumulative use of these agents result in abnormal brain pathology similar to that observed with Alzheimer’s Disease (AD).15”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [15]
The mechanism by which anticholinergic medications might contribute to dementia risk is biologically plausible.
“The mechanism by which anticholinergic medications might contribute to dementia risk has not been elucidated; however, a few lines of evidence suggest that it is biologically plausible.”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [15]
In a small autopsy study of patients with Parkinson's disease, participants receiving anticholinergic drugs for two years or longer had increased levels of AD neuropathology compared with those using for shorter durations.
“In a small autopsy study of patients with Parkinson’s disease, participants that were receiving anticholinergic drugs for two years or longer had increased levels of AD neuropathology compared with those using for shorter durations.15”
From Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study (2015) · cites this paper as [15]
Citations
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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
Targeting acetylcholinesterase and butyrylcholinesterase in dementia
Lane, R. M., Potkin, S. G., & Enz, A. (2005) · The International Journal of Neuropsychopharmacology · doi:10.1017/s1461145705005833 · Cited by 654
Anticholinergic drugs and risk of dementia: case-control study
Richardson, K., Fox, C., Maidment, I., Steel, N., Loke, Y. K., Arthur, A., Myint, P. K., Grossi, C. M., Mattishent, K., Bennett, K., et al. (2018) · BMJ · doi:10.1136/bmj.k1315 · Cited by 520
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
Weller, R. O., Boche, D., & Nicoll, J. A. R. (2009) · Acta Neuropathologica · doi:10.1007/s00401-009-0498-z · Cited by 297
Reimagining cholinergic therapy for Alzheimer’s disease
Giacobini, E., Cuello, A. C., & Fisher, A. (2022) · Brain · doi:10.1093/brain/awac096 · Cited by 187
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
Plants-derived neuroprotective agents: cutting the cycle of cell death through multiple mechanisms
Elufioye, T. O., Berida, T. I., & Habtemariam, S. (2017) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2017/3574012 · Cited by 107
Metadata
- Authors
- Perry, E. K., Kilford, L., Lees, A. J., Burn, D. J., & Perry, R. H.
- Affiliations
- Newcastle upon Tyne Hospital (GB)
- UCL Queen Square Institute of Neurology (GB)
- The Royal Free Hospital (GB)
- Corresponding author
- Perry, Elaine K.
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2003-07-25
- Volume
- 54
- Issue
- 2
- Pages
- 235-238
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2070495958
- Cited by
- 231
- References
- 2
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 6 · 2023: 4 · 2022: 6 · 2021: 9 · 2020: 12 · 2019: 13 · 2018: 6 · 2017: 7 · 2016: 7 · 2015: 12 · 2014: 7 · 2013: 10 · 2012: 9
- FWCI
- 9.87
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Clinical Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Parkinson's disease, Alzheimer's disease pathology, antimuscarinic agents, anticholinergic agents, muscarinic receptor blockade, amyloid plaques, neurofibrillary tangles, long-term drug treatment, elderly patients
- MeSH terms
- Aged, Alzheimer Disease, Antidepressive Agents, Tricyclic, Autopsy, Brain, Female, Humans, Male, Parkinson Disease, Neurofibrillary Tangles, Muscarinic Antagonists, Plaque, Amyloid
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