Long-term course and effectiveness of combination therapy in Alzheimer disease
Open accessAbstract
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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Longer-term prospective observational clinical patient cohort studies report reduced clinical decline in patients with AD treated at any stage.
“Longer-term prospective observational clinical patient cohort studies report reduced clinical decline in patients with AD treated at any stage.[114][115][116][117][118][119]”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [114]
Short-term randomized controlled trials, longer-term open-label extensions, and long-term observational prospective clinical cohort effectiveness studies support the safety and benefits of anti-AD treatments in combination, most frequently as memantine added on to a stable regimen of background cholinesterase inhibitor treatment.
“Short-term (6-12 months) RCTs (level I evidence), longer-term (12-36 months) openlabel extensions of RCTs (level II or III evidence), and long-term (2 to 5-plus years) observational prospective clinical cohort effectiveness studies (level II evidence) support the safety and benefits of anti-AD treatments in combination, most frequently as memantine added on to a stable regimen of background ChEI”
From The Alzheimer’s Disease Clinical Spectrum (2019) · cites this paper as [114]
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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.
- Venue
- Alzheimer Disease & Associated Disorders
- Published
- 2008-07
- Volume
- 22
- Issue
- 3
- Pages
- 209-221
- ISSN
- 0893-0341 (ISSN-L)
- 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
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pharmacology › 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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