Dr. Gary R. Cutter, professor in the department of biostatistics at the University of Alabama at Birmingham — collaborating with the primary author Dr. Richard E. Kennedy, assistant professor in UAB’s division of gerontology, geriatrics & palliative care, as well as biostatistics department colleague Dr. Guoqiao Wang — tested the a priori hypothesis that older participants differ in rates of decline on cognitive outcomes compared with younger participants, and examined the potential effect of age distributions on individual clinical trial outcomes.
From a meta-database of 18 studies from the Alzheimer’s Disease Cooperative Study and the Alzheimer’s Disease Neuroimaging Initiative, the researchers included a cohort of 2,793 participants for whom there were baseline demographic data and at least one post baseline cognitive assessment on the Alzheimer’s Disease Assessment Scale – cognitive subscale (ADAS-cog), Clinical Dementia Rating – Sum of Boxes (CDR-SB), or Mini-Mental State Examination (MMSE). They used mixed-effects models (random coefficient models) to estimate change on the outcomes across seven age groups ranging from younger than 61 years to older than 85 years after adjusting for education.
Significant worsening occurred in all age groups on all outcomes over time. The four older groups, ages 71 years and older, showed slower rates of decline on the ADAS-cog than the younger groups (p = 0.001). The older groups scored two–three, two–five, and four–six points better than the younger groups at 12, 18, and 24 months, respectively. There were similar differences across age groups for the MMSE, but not for the CDR-SB.
The differences in change on the ADAS-cog between older and younger participants are substantially greater than differences expected between experimental drugs and placebo in current trials or differences between marketed cholinesterase inhibitors and placebo. The clinical interpretation of change on the ADAS-cog or MMSE differs depending on age. Until predictors of decline are better understood, considering effects of age on rates of change is particularly important regarding clinical practice and outcomes of trials.
Drs. Cutter, Kennedy, and Wang, along with co-author Dr. Lon S. Schneider, professor at the University of Southern California Keck School of Medicine, presented their findings at The International Society for CNS Clinical Trials and Methodology (ISCTM) eleventh Annual Scientific Meeting, held in February in Washington, DC.
“Differences in Alzheimer Disease Clinical Trial Outcomes Based on Age of the Participants” was published online in March in the journal Neurology.
Journal article: http://www.neurology.org/content/84/11/1121.short