Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil
AbstractBackgroundThe extent and profiles of heterogeneity in cognitive functioning among participants in clinical trials of antidementia medication are unknown. We aimed to quantify and identify profiles of heterogeneity of cognition in Alzheimer’s disease.MethodsIndividual-level participant data w...
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| Format: | Article |
| Language: | English |
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Cambridge University Press
2021-01-01
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| Series: | European Psychiatry |
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| Online Access: | https://www.cambridge.org/core/product/identifier/S0924933821000080/type/journal_article |
| _version_ | 1811156391597965312 |
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| author | Stephen Z. Levine Yair Goldberg Kazufumi Yoshida Myrto Samara Andrea Cipriani Takeshi Iwatsubo Stefan Leucht Toshiaki A. Furawaka |
| author_facet | Stephen Z. Levine Yair Goldberg Kazufumi Yoshida Myrto Samara Andrea Cipriani Takeshi Iwatsubo Stefan Leucht Toshiaki A. Furawaka |
| author_sort | Stephen Z. Levine |
| collection | DOAJ |
| description | AbstractBackgroundThe extent and profiles of heterogeneity in cognitive functioning among participants in clinical trials of antidementia medication are unknown. We aimed to quantify and identify profiles of heterogeneity of cognition in Alzheimer’s disease.MethodsIndividual-level participant data were analyzed from five pivotal clinical trials of donepezil for Alzheimer’s disease (N = 2,919). Based on Alzheimer’s Disease Assessment Scale–Cognitive Subscale total scores from baseline up to week 12, a latent class model was used to identify heterogeneous groups. A logistic regression model was used to examine factors associated with group membership. Sensitivity analysis was conducted, restricted to the donepezil, and then the placebo arm.ResultsThe latent class model identified three classes labeled as low scorers (i.e., least cognitive impairment; N = 1,666, 76.04%), improvers (N = 27, 1.23%), and high scorers (N = 498, 22.73%). Logistic modeling showed that donepezil compared to placebo was significantly (p < 0.05) positively associated with membership in the improvers class (OR = 6.88, 95% CI = 2.03, 42.95), and negatively with high scorers (OR = 0.79, 95% CI = 0.64, 0.98). Sensitivity analysis restricted to the placebo, then donepezil arms replicated similar heterogeneity patterns.ConclusionsOur results inform clinicians regarding the extent of heterogeneity in cognitive functioning during treatment and contribute to trial design considerations. |
| first_indexed | 2024-04-10T04:49:39Z |
| format | Article |
| id | doaj.art-b556a059209b4db4a6d358230d6c29be |
| institution | Directory Open Access Journal |
| issn | 0924-9338 1778-3585 |
| language | English |
| last_indexed | 2024-04-10T04:49:39Z |
| publishDate | 2021-01-01 |
| publisher | Cambridge University Press |
| record_format | Article |
| series | European Psychiatry |
| spelling | doaj.art-b556a059209b4db4a6d358230d6c29be2023-03-09T12:33:55ZengCambridge University PressEuropean Psychiatry0924-93381778-35852021-01-016410.1192/j.eurpsy.2021.8Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezilStephen Z. Levine0https://orcid.org/0000-0002-5544-0420Yair Goldberg1https://orcid.org/0000-0002-4544-0910Kazufumi Yoshida2https://orcid.org/0000-0003-4475-8043Myrto Samara3https://orcid.org/0000-0002-6943-5091Andrea Cipriani4https://orcid.org/0000-0001-5179-8321Takeshi Iwatsubo5https://orcid.org/0000-0003-1160-8129Stefan Leucht6https://orcid.org/0000-0002-4934-4352Toshiaki A. Furawaka7https://orcid.org/0000-0003-2159-3776Department of Community Mental Health, University of Haifa, Haifa 3498838, IsraelFaculty of Industrial Engineering and Management, Technion-Israel Institute of Technology, Haifa, IsraelDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, JapanDepartment of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, Germany 3rd Department of Psychiatry, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki, GreeceDepartment of Psychiatry, University of Oxford, Oxford, United KingdomDepartment of Neuropathology, Graduate School of Medicine, The University of Tokyo, Tokyo, JapanDepartment of Psychiatry and Psychotherapy, Technical University of Munich, School of Medicine, Munich, GermanyDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine / School of Public Health, Kyoto, JapanAbstractBackgroundThe extent and profiles of heterogeneity in cognitive functioning among participants in clinical trials of antidementia medication are unknown. We aimed to quantify and identify profiles of heterogeneity of cognition in Alzheimer’s disease.MethodsIndividual-level participant data were analyzed from five pivotal clinical trials of donepezil for Alzheimer’s disease (N = 2,919). Based on Alzheimer’s Disease Assessment Scale–Cognitive Subscale total scores from baseline up to week 12, a latent class model was used to identify heterogeneous groups. A logistic regression model was used to examine factors associated with group membership. Sensitivity analysis was conducted, restricted to the donepezil, and then the placebo arm.ResultsThe latent class model identified three classes labeled as low scorers (i.e., least cognitive impairment; N = 1,666, 76.04%), improvers (N = 27, 1.23%), and high scorers (N = 498, 22.73%). Logistic modeling showed that donepezil compared to placebo was significantly (p < 0.05) positively associated with membership in the improvers class (OR = 6.88, 95% CI = 2.03, 42.95), and negatively with high scorers (OR = 0.79, 95% CI = 0.64, 0.98). Sensitivity analysis restricted to the placebo, then donepezil arms replicated similar heterogeneity patterns.ConclusionsOur results inform clinicians regarding the extent of heterogeneity in cognitive functioning during treatment and contribute to trial design considerations.https://www.cambridge.org/core/product/identifier/S0924933821000080/type/journal_articleClinical trialsdementiapsychometrics |
| spellingShingle | Stephen Z. Levine Yair Goldberg Kazufumi Yoshida Myrto Samara Andrea Cipriani Takeshi Iwatsubo Stefan Leucht Toshiaki A. Furawaka Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil European Psychiatry Clinical trials dementia psychometrics |
| title | Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil |
| title_full | Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil |
| title_fullStr | Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil |
| title_full_unstemmed | Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil |
| title_short | Quantifying the heterogeneity of cognitive functioning in Alzheimer’s disease to extend the placebo-treatment dichotomy: Latent class analysis of individual-participant data from five pivotal randomized clinical trials of donepezil |
| title_sort | quantifying the heterogeneity of cognitive functioning in alzheimer s disease to extend the placebo treatment dichotomy latent class analysis of individual participant data from five pivotal randomized clinical trials of donepezil |
| topic | Clinical trials dementia psychometrics |
| url | https://www.cambridge.org/core/product/identifier/S0924933821000080/type/journal_article |
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