Cholinesterase inhibitors and add-on nutritional supplements in Alzheimer's disease
Abstract
To date, single drug and nutrient-based interventions have failed to show a clinically relevant effect on Alzheimer's disease (AD). Multidomain interventions may alleviate symptoms and alter the disease course in a synergistic manner. This systematic review examines the effect of adding nutritional supplementation to cholinesterase inhibitors. A systematic PubMed and Cochrane search resulted in nine high quality studies. The studies had low to moderate risk of bias and focused on oxidative stress, homocysteine levels, membrane fluidity, inflammation and acetylcholine levels. Only the use of vitamin E supplements could reduce the rate of functional decline when combined with cholinesterase inhibitors in one study, whereas cognition was not affected in both this and other studies. None of the other nutritional supplements showed convincing evidence of a beneficial effect when combined with cholinesterase inhibitors. This shows that cognitive and functional improvement is difficult to achieve in patients with AD, despite epidemiological data and evidence of biological effects of nutritional supplements. Addressing one disease pathway in addition to cholinesterase inhibitor therapy is probably insufficient to alter the course of the disease. Personalized, multifactorial interventions may be more successful in improving cognition and daily functioning.
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Classical antioxidants vitamin E, selegiline, and coenzyme Q10 have not demonstrated consistent cognitive benefit in AD patients, even when combined with cholinesterase inhibitors.
“Classical agents such as vitamin E, selegiline, and coenzyme Q10 have not demonstrated consistent cognitive benefit in patients, even when combined with cholinesterase inhibitors [104].”
From Toward a Unified Framework in Molecular Neurobiology of Alzheimer’s Disease: Revisiting the Pathophysiological Hypotheses (2026) · cites this paper as [104]
Cites
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- Authors
- Rijpma, A., Meulenbroek, O., & Olde Rikkert, M. G. M.
- Affiliations
- Radboud University Medical Center (NL)
- Radboud University Nijmegen (NL)
- Corresponding author
- Rijpma, A.
- ORCID
- Rijpma, A.
- Venue
- Ageing Research Reviews
- Publisher
- Elsevier BV
- Published
- 2014-07
- Volume
- 16
- Pages
- 105-112
- ISSN
- 1568-1637 (ISSN-L)
- OpenAlex
- W2120640926
- Cited by
- 26
- References
- 4
- Citations by year
- 2025: 4 · 2021: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 1
- FWCI
- 0.64
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Ageing Research Reviews (publishedVersion)
- PubMed (publishedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, cholinesterase inhibitors, dietary supplements, vitamin E, oxidative stress, homocysteine, membrane fluidity, inflammation, acetylcholine, functional decline, cognition, multidomain intervention, personalized interventions
- MeSH terms
- Aged, Alzheimer Disease, Cholinesterase Inhibitors, Cognition, Drug Therapy, Combination, Female, Humans, Male, Nutritional Status, Randomized Controlled Trials as Topic, Treatment Outcome, Dietary Supplements
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