Bryostatin Placebo-Controlled Trials Indicate Cognitive Restoration Above Baseline for Advanced Alzheimer's Disease in the Absence of Memantine1
| Autor: | Richard E. Thompson, Alan J. Tuchman, Daniel L. Alkon |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
General Neuroscience
General Medicine Bryostatins Mental Status and Dementia Tests Psychiatry and Mental health Clinical Psychology Mice Clinical Trials Phase II as Topic Cognition Treatment Outcome Double-Blind Method Alzheimer Disease Memantine Animals Humans Controlled Clinical Trials as Topic Geriatrics and Gerontology |
| Zdroj: | Journal of Alzheimer's disease : JAD. 86(3) |
| ISSN: | 1875-8908 |
| Popis: | Background: In pre-clinical studies of Alzheimer’s disease (AD) transgenic mice, bryostatin restored synaptic connections, prevented neuronal death, reduced amyloid plaques, and reduced neurofibrillary tangles. Objective: Within pre-specified cohorts of advanced AD patients in two double-blind placebo-controlled bryostatin Phase II trials, to conduct exploratory statistical analyses of patients with identical conditions of enrollment and treatment. Methods: Severe Impairment Battery (SIB) scores above baseline at 5, 9, and 13 weeks were analyzed initially in the complete cases, with multiple imputation methods based on an iterative Markov chain Monte Carlo algorithm used for missing SIB scores. To mitigate confounding by a chance imbalance of 4.9 SIB baseline scores (Study #203), each patient was used as their own control with differences in 13-week SIB from baseline in single trial and pooled analyses to measure benefit at 13 weeks using general estimating equations (GEE) modeling. Results: Patients treated with bryostatin pre-specified at Mini-Mental State Examination scores 10–14, without memantine, showed baseline balance, complete safety, and SIB improvements at 13 weeks with multiple imputation analysis: Study #203 = 4.1 SIB points above baseline (p = 0.005), and Study #202 = 4.2 SIB points above baseline (p = 0.016). An increased power (N = 95) “pooled analysis” showed an increased SIB over time and a higher mean SIB at 13 weeks in the bryostatin treatment group (p |
| Databáze: | OpenAIRE |
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