Personalized Prediction of Alzheimer's Disease and Its Treatment Effects by Donepezil: An Individual Participant Data Meta-Analysis of Eight Randomized Controlled Trials.

Yoshida, Kazufumi; Seo, Michael; Luo, Yan; Sahker, Ethan; Cipriani, Andrea; Leucht, Stefan; Iwatsubo, Takeshi; Efthimiou, Orestis; Furukawa, Toshiaki A (2022). Personalized Prediction of Alzheimer's Disease and Its Treatment Effects by Donepezil: An Individual Participant Data Meta-Analysis of Eight Randomized Controlled Trials. Journal of Alzheimer's disease, 89(4), pp. 1143-1157. IOS Press 10.3233/JAD-220263

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Social and Preventive Medicine (ISPM)
04 Faculty of Medicine > Medical Education > Institute of General Practice and Primary Care (BIHAM)

Graduate School:

Graduate School for Health Sciences (GHS)

UniBE Contributor:

Seo, Michael Juhn Uh, Efthimiou, Orestis

Subjects:

600 Technology > 610 Medicine & health
300 Social sciences, sociology & anthropology > 360 Social problems & social services

ISSN:

1875-8908

Publisher:

IOS Press

Language:

English

Submitter:

Pubmed Import

Date Deposited:

24 Aug 2022 13:28

Last Modified:

09 Dec 2022 09:32

Publisher DOI:

10.3233/JAD-220263

PubMed ID:

35988219

Uncontrolled Keywords:

Alzheimer’s disease cognition donepezil effect modifier meta-analysis prognosis

BORIS DOI:

10.48350/172279

URI:

https://boris.unibe.ch/id/eprint/172279

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