Effectiveness of antidementia drugs in delaying Alzheimer's disease progression

Rountree, Susan D.; Atri, Alireza; Lopez, Oscar L.; Doody, Rachelle S.

doi:10.1016/j.jalz.2012.01.002

Cited by 97Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCholinesterase and Neurodegenerative Diseases

Effectiveness of antidementia drugs in delaying Alzheimer's disease progression

Rountree, Susan D., Atri, Alireza, Lopez, Oscar L., Doody, Rachelle S.·2013·Alzheimer's & Dementia

DOI 10.1016/j.jalz.2012.01.002

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Abstract

BACKGROUND: Randomized controlled trials (RCTs) provide safety and efficacy data for regulatory approval of antidementia drugs, but offer limited data regarding real-world effectiveness. Long-term observational controlled studies (LTOCs) extend our understanding by providing longitudinal data across multiple stages of Alzheimer's disease (AD). METHODS: Comparisons of strengths, limitations, evidence level, and results for monotherapy (cholinesterase inhibitors) and combination therapy (cholinesterase inhibitors + memantine) in RCTs versus LTOCs were made. RESULTS: Similar to RCTs, LTOCs have shown that both monotherapy and combination therapy are associated with slower cognitive and functional decline. Combination therapy is associated with better cognitive outcomes and greater delays in time to nursing home admission versus monotherapy or no treatment. Persistent antidementia drug treatment is associated with slower decline in cognition, daily function, and global severity, even in patients with advanced disease. CONCLUSIONS: LTOCs provide complementary evidence regarding effectiveness of antidementia therapy over many years, a time course relevant to AD management. These findings also provide compelling arguments in favor of using LTOCs to estimate effectiveness, risk-benefit, and costs of AD treatments.

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The FDA has approved donepezil and rivastigmine for mild, moderate, and severe Alzheimer's disease, respectively, while galantamine has been approved for mild and moderate Alzheimer's disease.
“The FDA has approved donepezil and rivastigmine for mild, moderate, and severe AD, respectively, while galantamine has been approved for mild and moderate AD (Rountree et al., 2013).”
From An update on the novel and approved drugs for Alzheimer disease (2022) · cites this paper as Rountree et al., 2013
Anti-AD therapies, whether as cholinesterase inhibitor or memantine monotherapy or as add-on dual combination therapy, have demonstrated short-term and long-term benefits to reduce decline in cognition and function.
“A pharmacologic foundation of anti-AD therapies, whether with a ChEI or memantine monotherapy, or, ultimately, combined together as add-on dual combination therapy, most often as memantine added on to stable background ChEI treatment, have demonstrated benefits in the short-term and long-term to reduce decline in cognition and function”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [65]
In more than 40 short-term randomized controlled trials using placebos over 24 to 52 weeks and in meta-analyses of randomized controlled trials, all 3 cholinesterase inhibitors have demonstrated small to medium effect size treatment benefits at the subject-group level in improving, stabilizing, or delaying decline in cognition, activities of daily living, and global status, and in ameliorating BPS
“In more than 40 short-term randomized controlled trials (RCTs) using placebos over 24 to 52 weeks investigating efficacy, and in meta-analyses of RCTs, all 3 ChEIs have demonstrated small to medium effect size treatment benefits at the sibject-group level in terms of improving, stabilizing, or delaying decline in cognition, ADL, and global status, and in ameliorating BPSD and caregiver burden.35,”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [65]
Anti-AD therapies delay nursing home placement without prolongation of time to death.
“and to delay nursing home placement without prolongation of time to death.64,65”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [65]
Anti-AD therapies retard the emergence and impact of neuropsychiatric symptoms.
“retard the emergence and impact of neuropsychiatric symptoms”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [65]

All three acetylcholinesterase inhibitors have proved treatment benefits in delaying decline, stabilizing, or even improving cognition and activities of daily living in randomized placebo-controlled trials up to 52 weeks duration.
“All 3 AChEIs have proved their treatment benefits in delaying decline, stabilizing, or even improving cognition and activities of daily living in randomized placebo-controlled trials up to 52 weeks duration.10,18”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]
Donepezil and galantamine selectively and reversibly inhibit acetylcholinesterase, whereas rivastigmine is a pseudo-irreversible inhibitor of acetylcholinesterase and butyrylcholinesterase.
“Donepezil and galantamine inhibit selectively and reversibly the acetylcholinesterase, whereas rivastigmine is a “pseudo-irreversible” inhibitor of acetylcholinesterase and butyrylcholinesterase.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]
Acetylcholinesterase inhibitors are contraindicated in severe cardiac arrhythmias, especially bradycardia or syncope, active peptic ulcer or gastrointestinal bleeding history, and uncontrolled seizures.
“Thus, AChEIs are contraindicated in conditions including severe cardiac arrhythmias, especially bradycardia or syncope. They are also contraindicated in active peptic ulcer or gastrointestinal bleeding history and uncontrolled seizures.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]
Pharmacokinetic characteristics differ among acetylcholinesterase inhibitors: donepezil and galantamine are primarily eliminated by hepatic metabolism, whereas rivastigmine is eliminated by liver and intestine metabolism.
“Pharmacokinetic characteristics differ among AChEIs: the primary route of elimination for donepezil and galantamine is hepatic metabolism, whereas for rivastigmine is liver and intestine metabolism.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]
Acetylcholinesterase inhibitors may trigger bradycardia and increase the risk of syncope.
“The AChEIs may also trigger bradycardia and increase the risk of syncope.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]
Donepezil and rivastigmine have been approved by FDA for mild, moderate, and severe Alzheimer disease, whereas galantamine is approved for mild and moderate Alzheimer disease.
“Donepezil and rivastigmine have been approved by FDA for mild, moderate, and severe AD, whereas galantamine for mild and moderate AD.18”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]
Significant efficacy differences among the acetylcholinesterase inhibitors have not been reported.
“Significant efficacy differences among the AChEIs have not been reported.”
From Current and Future Treatments in Alzheimer Disease: An Update (2020) · cites this paper as [18]

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Authors: Rountree, S. D., Atri, A., Lopez, O. L., & Doody, R. S.
Affiliations: Baylor College of Medicine (US)
Edith Nourse Rogers Memorial Veterans Hospital (US)
Department of Neurology University of Pittsburgh School of Medicine Pittsburgh PA USA
Corresponding author: Rountree, Susan D.
ORCID: Atri, Alireza
Venue: Alzheimer's & Dementia
Publisher: Wiley
Published: 2012-10-24
Volume: 9
Issue: 3
Pages: 338-345
ISSN: 1552-5260 (ISSN-L)
1552-5279
DOI: 10.1016/j.jalz.2012.01.002
OpenAlex: W2093615841
Cited by: 97
References: 58
Citations by year: 2026: 4 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 1 · 2021: 7 · 2020: 7 · 2019: 11 · 2018: 9 · 2017: 8 · 2016: 5 · 2015: 11 · 2014: 12 · 2013: 3
FWCI: 5.92
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Alzheimer s & Dementia (publishedVersion)
PubMed (publishedVersion)
Funders: Forest Laboratories
National Institute on Aging
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, anti-dementia drugs
MeSH terms: Donepezil, Aged, Alzheimer Disease, Cholinesterase Inhibitors, Dementia, Humans, Indans, Memantine, Piperidines, Dopamine Agents, Prevalence, Randomized Controlled Trials as Topic, Nootropic Agents, Evidence-Based Medicine

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Effectiveness of antidementia drugs in delaying Alzheimer's disease progression

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