Dose-dependent slowing in cognitive decline from baseline on ADAS-Cog
was also observed for BAN2401, with the highest treatment dose of BAN2401 demonstrating a significant slowing of clinical decline compared to placebo at 18 months (47% slower decline, p=0.017).
The analysis, as shown in Table 4, revealed that the Understanding score was significantly predicted by the ADAS-Cog
total score ([beta] = -0.4, p = 0.01) and the CVFT score ([beta] = 0.3, p = 0.04), and that the relationship accounted for about 45% of the variance of the Understanding score.
After 18 months, the mean placebo decline rates were 6 points on the ADAS-cog
, 11 points on the ADAS-ADL, and 2.7 points on the CDR-sb.
Secondary endpoints included the change from baseline on a 13-item version of the ADAS-Cog
, the Mini Mental State Examination, the Clinician's Interview-Based Impression of Change, the Neuropsychiatric Inventory, and the Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL).
After 18 weeks, the intervention group had a decline of 4.6 points on the ADAS-cog
(with lower scores being better) while the usual care group had an increase of 2.4 points on the measure, for an effect size of 0.76.
By the end of the study, those who took dimebon actually gained about 2 points on the Alzheimer's Disease Assessment Scale-Cognition (ADAS-cog
), while those taking placebo had declined almost 6 points from baseline.
The key endpoints are Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-cog
), Activities of Daily Living (ADL), and the Clinical Global Impression of Change Scale (CGIC).
Measures used for participants included the Alzheimer's Disease Assessment Scale--cognitive subscale (ADAS-cog
) to measure cognitive function, the Quality of Life in Alzheimer's Disease (QoL-AD) tool to measure quality of life, and the Short Physical Performance Battery (SPPB) to measure physical function.
Cognitive tests administered including the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog
), the Wechsler Adult Intelligence Scale-Ill (WAIS-III), the Boston Naming Test, the Controlled Oral Word Association Test, the Clock Drawing Test, the Wechsler Memory Scale-Revised (WMS-R), the Rey Auditory Verbal Learning Test, the Trail Making Test, and the Beck Depression Inventory.
Primary outcomes in the study were change in the cognitive portion of the Alzheimer's Disease Assessment Scale (ADAS-cog
) and the Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC), both administered quarterly.
The investigators used observational data from ADNI to show that, out of 675 measurements made at time points of 0, 6, 12, and 24 months, data from ADAS-Cog
total scores spanned the entire range of the scale and had no floor or ceiling effects that would reduce its ability to measure changes and differences in lower-functioning or higher-functioning patients, respectively However, 8 of the scale's 11 components (all except for word recall, word recognition, and orientation) had statistically significant ceiling effects with a skewed distribution of scores (Alzheimers Dement.
Memantine exerted "no significant effects" whether patients with mild AD were assessed using the Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-cog
), the Clinician's Interview-Based Impression of Change Plus Caregiver's Input (CIBIC-plus), the Alzheimer Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, or the Neuropsychiatric Inventory (NPI).