Bruce Albala, United States of America
University of California, Irvine Center for Clinical ResearchAuthor Of 2 Presentations
VALIDITY AND SENSITIVITY OF THE COGSTATE BRIEF BATTERY FOR IN-CLINIC AND AT-HOME COGNITIVE ASSESSMENT IN ADNI-3
Abstract
Aims
The Cogstate Brief Battery (CBB) is a computerized cognitive assessment validated for Alzheimer’s disease (AD) and unsupervised use. The CBB assesses processing speed, attention, visual learning, and working memory. The CBB is offered to cognitively normal (CN) and mild cognitive impairment (MCI) participants in ADNI-3. In-clinic visits are completed annually for MCI and every other year for CN, with both groups completing unsupervised assessments at-home within 14 days of the first in-clinic visit and every 3 months.
Methods
CBB data were analyzed for eight outcome measures to evaluate sensitivity to disease status (CN, MCI), effect of setting (in-clinic, at-home), and change over time.
Results
Data were analyzed for 697 participants (459 CN, 222 MCI, 12 AD). Fewer participants completed a first at-home (n=365) versus a first in-clinic assessment (n=629). Statistically significant, small-moderate effect size differences between CN and MCI/AD (0.34 to 0.72) were evident at the first in-clinic visit. Effect size differences for in-clinic versus first at-home assessment, were small (<0.01 to 0.29) and non-significant, except for faster working memory reaction times at-home. Linear mixed models for participants completing 24 months (n=171), showed evidence for divergence between CN and MCI over time, a finding most evident on the learning and memory tests. Inclusion of amyloid status supported a predicted pattern of poorer cognition in amyloid positive participants.
Conclusions
Data from ADNI-3 support the validity and sensitivity of the CBB for unsupervised, at-home assessment, demonstrating known groups validity, equivalence between in-clinic and at-home assessment, and longitudinal sensitivity.
EFFICACY AND SAFETY OF ELENBECESTAT IN SUBJECTS WITH EARLY ALZHEIMER'S DISEASE: RESULTS FROM THE MISSIONAD PHASE 3 PROGRAM
Abstract
Aims
To evaluate the BACE inhibitor elenbecestat in early Alzheimer’s Disease (EAD).
Methods
The MissionAD program comprised two randomized, placebo-controlled phase 3 studies. Patients with EAD were randomized 1:1 to either once-daily elenbecestat (50 mg) or placebo for 24 months. The primary endpoint was CDR-SB at 24 months in the combined studies. Key secondary endpoints included AD Composite Score (ADCOMS) and amyloid PET.
Results
Following recommendation of the elenbecestat DSMB, the studies were terminated early due to an unfavourable risk-benefit ratio. 2209 patients were treated (elenbecestat:1101;placebo:1108) and 189 had a 24-month CDR assessment. No differences were observed in least squares (LS) mean [SE] change from baseline in CDR-SB at 24 months (elenbecestat: 1.99 [0.146]; placebo: 2.17 [0.142]; LS mean difference [95% CI]: -0.17 [-0.57, 0.22]). For ADCOMS at 24 months, no differences were observed in LS Mean (SE) change from baseline (elenbecestat: 0.23 [0.015]; placebo: 0.24 [0.014]; LS mean difference [95% CI]: -0.02 [-0.06, 0.02]). LS mean (SE) change from baseline in amyloid PET centiloids at 24 months was -5.02 (2.046) for elenbecestat and 7.81 (2.500) for placebo (LS mean differences [95% CI] was –12.83 [-18.79, -6.88], nominal p<0.001). Incidence of adverse events were similar between groups with lymphopenia, rash, dizziness, weight loss, and abnormal dreams occurring more frequently with elenbecestat.
Conclusions
There was no evidence of a treatment effect on CDR-SB or ADCOMS for elenbecestat in the early terminated MissionAD studies.