Cited by 2,380Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCholinesterase and Neurodegenerative Diseases

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

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Abstract

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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  1. Holm S, 1979, Scand J Stat, 6, 65

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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
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
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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