The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.
A Controlled Trial of Selegiline, Alpha-Tocopherol, or Both as Treatment for Alzheimer's Disease
Open accessAbstract
BACKGROUND: There is evidence that medications or vitamins that increase the levels of brain catecholamines and protect against oxidative damage may reduce the neuronal damage and slow the progression of Alzheimer's disease. METHODS: We conducted a double-blind, placebo-controlled, randomized, multicenter trial in patients with Alzheimer's disease of moderate severity. A total of 341 patients received the selective monoamine oxidase inhibitor selegiline (10 mg a day), alpha-tocopherol (vitamin E, 2000 IU a day), both selegiline and alpha-tocopherol, or placebo for two years. The primary outcome was the time to the occurrence of any of the following: death, institutionalization, loss of the ability to perform basic activities of daily living, or severe dementia (defined as a Clinical Dementia Rating of 3). RESULTS: Despite random assignment, the baseline score on the Mini-Mental State Examination was higher in the placebo group than in the other three groups, and this variable was highly predictive of the primary outcome (P<0.001). In the unadjusted analyses, there was no statistically significant difference in the outcomes among the four groups. In analyses that included the base-line score on the Mini-Mental State Examination as a covariate, there were significant delays in the time to the primary outcome for the patients treated with selegiline (median time, 655 days; P=0.012), alpha-tocopherol (670 days, P=0.001) or combination therapy (585 days, P=0.049), as compared with the placebo group (440 days). CONCLUSIONS: In patients with moderately severe impairment from Alzheimer's disease, treatment with selegiline or alpha-tocopherol slows the progression of disease.
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“To date, none of the tested compounds have proven effective (Sano et al., 1997; Petersen et al., 2005; Pham and Plakogiannis, 2005; DeKosky et al., 2008).”
From The mitochondria-targeted antioxidant MitoQ prevents loss of spatial memory retention and early neuropathology in a transgenic mouse model of Alzheimer’s disease (2011) · cites this paper as Sano et al., 1997
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“Following a report of success of high-dose vitamin E in keeping late-stage AD patients out of long-term care facilities longer than patients on a placebo81, other studies with vitamin E have been less impressive70,78,80.”
From Oxidative stress, dysfunctional glucose metabolism and Alzheimer disease (2019) · cites this paper as [81]
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“there were no concerning safely signals or increased mortality with high-dose vitamin E. 127,128”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [127]
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“high-dose vitamin E (1000 IU twice daily was the regimen tested) may be considered based on results of 2 RCTs that supported approximately 20% lower rate of ADL decline over approximately 2 to 3 years; there were no concerning safely signals or increased mortality with high-dose vitamin E. 127,128”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [127]
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Metadata
- Authors
- Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman, M., Woodbury, P., Growdon, J., Cotman, C. W., Pfeiffer, E., Schneider, L. S., & Thal, L. J.
- Affiliations
- University of California San Diego (US)
- Harvard University (US)
- University of California, Irvine (US)
- University of South Florida (US)
- University of Southern California (US)
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 1997-04-24
- Volume
- 336
- Issue
- 17
- Pages
- 1216-1222
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- OpenAlex
- W2326200998
- Cited by
- 2,380
- References
- 36
- Citations by year
- 2026: 19 · 2025: 23 · 2024: 39 · 2023: 39 · 2022: 41 · 2021: 38 · 2020: 44 · 2019: 43 · 2018: 44 · 2017: 47 · 2016: 55 · 2015: 54 · 2014: 72 · 2013: 62 · 2012: 82
- FWCI
- 118.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (U01‐AG10483, U01AG010483, U19AG010483)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology (medical) › Cholinesterase and Neurodegenerative Diseases
- Keywords
- Alzheimer's disease, selegiline, alpha-tocopherol, vitamin E, monoamine oxidase inhibitors, combination therapy, disease progression, dementia, activities of daily living, Mini-Mental State Examination, oxidative stress, catecholamines
- MeSH terms
- Activities of Daily Living, Aged, Alzheimer Disease, Cognition, Double-Blind Method, Drug Combinations, Female, Humans, Institutionalization, Male, Mental Status Schedule, Monoamine Oxidase Inhibitors, Selegiline, Vitamin E, Proportional Hazards Models, Treatment Outcome, Disease Progression
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