Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials
Background:Patient characteristics may predict the progression of Alzheimer’s disease (AD) and may moderate the effects of donepezil. Objective:To build a personalized prediction model for patients with AD and to estimate patient-specific treatment effects of donepezil, using individual patient char...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
IOS Press
2022
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| _version_ | 1797108163437133824 |
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| author | Yoshida, K Seo, M Luo, Y Sahker, E Cipriani, A Leucht, S Iwatsubo, T Efthimiou, O Furukawa, TA |
| author_facet | Yoshida, K Seo, M Luo, Y Sahker, E Cipriani, A Leucht, S Iwatsubo, T Efthimiou, O Furukawa, TA |
| author_sort | Yoshida, K |
| collection | OXFORD |
| description | Background:Patient characteristics may predict the progression of Alzheimer’s disease (AD) and may moderate the effects of donepezil. Objective:To build a personalized prediction model for patients with AD and to estimate patient-specific treatment effects of donepezil, using individual patient characteristics. Methods:We systematically searched for all double-masked randomized controlled trials comparing oral donepezil and pill placebo in the treatment of AD and requested individual participant data through its developer, Eisai. The primary outcome was cognitive function at 24 weeks, measured with the Alzheimer’s Disease Assessment Scale-cognitive component (ADAS-cog). We built a Bayesian meta-analytical prediction model for patients receiving placebo and we performed an individual patient data meta-analysis to estimate patient-level treatment effects. Results:Eight studies with 3,156 participants were included. The Bayesian prediction model suggested that more severe cognitive and global function at baseline and younger age were associated with worse cognitive function at 24 weeks. The individual participant data meta-analysis showed that, on average, donepezil was superior to placebo in cognitive function (ADAS-cog scores, –3.2; 95% Credible Interval (CrI) –4.2 to –2.1). In addition, our results suggested that antipsychotic drug use at baseline might be associated with a lower effect of donepezil in ADAS-cog (2.0; 95% CrI, –0.02 to 4.3). Conclusion:Although our results suggested that donepezil is somewhat efficacious for cognitive function for most patients with AD, use of antipsychotic drugs may be associated with lower efficacy of the drug. Future research with larger sample sizes, more patient covariates, and longer treatment duration is needed. |
| first_indexed | 2024-03-07T07:25:37Z |
| format | Journal article |
| id | oxford-uuid:55e81cfe-ba12-4f08-8bbd-d0c22514ded2 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:25:37Z |
| publishDate | 2022 |
| publisher | IOS Press |
| record_format | dspace |
| spelling | oxford-uuid:55e81cfe-ba12-4f08-8bbd-d0c22514ded22022-11-17T06:30:33ZPersonalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trialsJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:55e81cfe-ba12-4f08-8bbd-d0c22514ded2EnglishSymplectic ElementsIOS Press2022Yoshida, KSeo, MLuo, YSahker, ECipriani, ALeucht, SIwatsubo, TEfthimiou, OFurukawa, TABackground:Patient characteristics may predict the progression of Alzheimer’s disease (AD) and may moderate the effects of donepezil. Objective:To build a personalized prediction model for patients with AD and to estimate patient-specific treatment effects of donepezil, using individual patient characteristics. Methods:We systematically searched for all double-masked randomized controlled trials comparing oral donepezil and pill placebo in the treatment of AD and requested individual participant data through its developer, Eisai. The primary outcome was cognitive function at 24 weeks, measured with the Alzheimer’s Disease Assessment Scale-cognitive component (ADAS-cog). We built a Bayesian meta-analytical prediction model for patients receiving placebo and we performed an individual patient data meta-analysis to estimate patient-level treatment effects. Results:Eight studies with 3,156 participants were included. The Bayesian prediction model suggested that more severe cognitive and global function at baseline and younger age were associated with worse cognitive function at 24 weeks. The individual participant data meta-analysis showed that, on average, donepezil was superior to placebo in cognitive function (ADAS-cog scores, –3.2; 95% Credible Interval (CrI) –4.2 to –2.1). In addition, our results suggested that antipsychotic drug use at baseline might be associated with a lower effect of donepezil in ADAS-cog (2.0; 95% CrI, –0.02 to 4.3). Conclusion:Although our results suggested that donepezil is somewhat efficacious for cognitive function for most patients with AD, use of antipsychotic drugs may be associated with lower efficacy of the drug. Future research with larger sample sizes, more patient covariates, and longer treatment duration is needed. |
| spellingShingle | Yoshida, K Seo, M Luo, Y Sahker, E Cipriani, A Leucht, S Iwatsubo, T Efthimiou, O Furukawa, TA Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials |
| title | Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials |
| title_full | Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials |
| title_fullStr | Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials |
| title_full_unstemmed | Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials |
| title_short | Personalized prediction of Alzheimer's disease and its treatment effects by donepezil: an individual participant data meta-analysis of eight randomized controlled trials |
| title_sort | personalized prediction of alzheimer s disease and its treatment effects by donepezil an individual participant data meta analysis of eight randomized controlled trials |
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