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.
Clinical trials
dementia
psychometrics
Journal
European psychiatry : the journal of the Association of European Psychiatrists
ISSN: 1778-3585
Titre abrégé: Eur Psychiatry
Pays: England
ID NLM: 9111820
Informations de publication
Date de publication:
15 02 2021
15 02 2021
Historique:
pubmed:
16
2
2021
medline:
20
11
2021
entrez:
15
2
2021
Statut:
epublish
Résumé
The 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. Individual-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. The 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. Our results inform clinicians regarding the extent of heterogeneity in cognitive functioning during treatment and contribute to trial design considerations.
Sections du résumé
BACKGROUND
The 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.
METHODS
Individual-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.
RESULTS
The 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.
CONCLUSIONS
Our results inform clinicians regarding the extent of heterogeneity in cognitive functioning during treatment and contribute to trial design considerations.
Identifiants
pubmed: 33583479
doi: 10.1192/j.eurpsy.2021.8
pii: S0924933821000080
pmc: PMC8057455
doi:
Substances chimiques
Nootropic Agents
0
Donepezil
8SSC91326P
Types de publication
Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e16Subventions
Organisme : Department of Health
ID : RP-2017-08-ST2-006
Pays : United Kingdom
Organisme : Department of Health
ID : BRC-1215-20005
Pays : United Kingdom
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