Cited by 230Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCholinesterase and Neurodegenerative Diseases

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Long-term Course and Effectiveness of Combination Therapy in Alzheimer Disease

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Atri, Alireza, Shaughnessy, Lynn W., Locascio, Joseph J., Growdon, John H.·2008·Alzheimer Disease & Associated Disorders

DOI 10.1097/wad.0b013e31816653bcPMC PMC2718545

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Abstract

OBJECTIVE: To compare the real-world clinical effectiveness and long-term clinical trajectory in patients with Alzheimer disease (AD) treated with combination (COMBO) therapy consisting of cholinesterase-inhibitor (CI) plus memantine (MEM) versus CI alone versus no treatment with either. METHODS: Three hundred eighty-two subjects with probable AD underwent serial clinical evaluations at a memory disorders unit. Cognition was assessed by the Information-Memory-Concentration subscale of the Blessed Dementia Scale (BDS) and function was assessed by the Weintraub Activities of Daily Living Scale (ADL) at 6-month intervals. One hundred forty-four subjects received standard care without CI or MEM (NO-RX), 122 received CI monotherapy, and 116 received COMBO therapy with CI plus MEM. Mean follow-up was 30 months (4.1 visits) and mean cumulative medication treatment time was 22.5 months. Rates of decline were analyzed using mixed-effects regression models, and Cohen's d effect sizes were calculated annually for years 1 to 4. RESULTS: Covarying for baseline scores, age, education, and duration of illness, the COMBO group had significantly lower mean annualized rates of deterioration in BDS and ADL scores compared with the CI (P<0.001; Cohen's dBDS=0.10-0.34 and dADL=0.23-0.46 at 1 to 2 y) and NO-RX groups (P<0.001; Cohen's dBDS=0.56-0.73 and dADL=0.32-0.48 at 1 to 2 y). For the COMBO group, Cohen's d effect sizes increased with treatment duration. Similar comparisons significantly favored the CI over the NO-RX group on the BDS. CONCLUSIONS: COMBO therapy slows cognitive and functional decline in AD compared with CI monotherapy and no treatment. These benefits had small-to-medium effect sizes that increased with time on treatment and were sustained for years.

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Authors: Atri, A., Shaughnessy, L. W., Locascio, J. J., & Growdon, J. H.
Affiliations: Harvard University (US)
Corresponding author: Atri, Alireza
Shaughnessy, Lynn W.
Locascio, Joseph J.
Growdon, John H.
ORCID: Atri, Alireza
Locascio, Joseph J.
Venue: Alzheimer Disease & Associated Disorders
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2008-07
Volume: 22
Issue: 3
Pages: 209-221
ISSN: 0893-0341 (ISSN-L)
DOI: 10.1097/wad.0b013e31816653bc
PMC: PMC2718545
OpenAlex: W2133239607
Cited by: 230
References: 54
Citations by year: 2026: 3 · 2025: 3 · 2024: 10 · 2023: 7 · 2022: 14 · 2021: 2 · 2020: 8 · 2019: 6 · 2018: 10 · 2017: 8 · 2016: 14 · 2015: 20 · 2014: 15 · 2013: 21 · 2012: 33
FWCI: 12.88
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Alzheimer Disease & Associated Disorders (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: Massachusetts General Hospital
National Institute on Aging (5P50AG05134, 1K23 AG27171-01, K23AG027171, P50AG005134)
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, combination therapy, cholinesterase inhibitors, memantine, cognitive decline, functional decline, activities of daily living, long-term treatment effectiveness, real-world clinical outcomes, treatment duration
MeSH terms: Activities of Daily Living, Aged, Alzheimer Disease, Cholinesterase Inhibitors, Cognition, Cognition Disorders, Drug Therapy, Combination, Female, Humans, Male, Memantine, Time, Dopamine Agents, Treatment Outcome

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