BACKGROUND: Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. OBJECTIVE: To determine the influence of age on AD course in a clinical trial setting. DESIGN: Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. SETTING: Alzheimer disease research centers from across the United States. PATIENTS: Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. MAIN OUTCOME MEASURES: The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. RESULTS: Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. CONCLUSION: Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.
BACKGROUND: Factors that affect the rate of progression of Alzheimer disease (AD) need to be considered in the clinical trial designs of potential disease-modifying therapies. OBJECTIVE: To determine the influence of age on AD course in a clinical trial setting. DESIGN: Pooled cohort study from 3 AD clinical trials of 18-month duration conducted by the Alzheimer Disease Cooperative Study group. SETTING:Alzheimer disease research centers from across the United States. PATIENTS: Four hundred seventy-one subjects with mild to moderate AD assigned to the placebo arm of 3 clinical trials. MAIN OUTCOME MEASURES: The relationships between baseline age and rate of change in the Alzheimer Disease Assessment Scale–cognitive subscale (ADAS-cog) 11, Mini-Mental State Examination, Clinical Dementia Rating scale Sum of Boxes score, Alzheimer Disease Cooperative Study–activities of daily living scale, and Neuropsychiatric Inventory were analyzed using a mixed-effect regression model. Sample size calculation for possible future AD clinical trials lasting 18 months using the results of the change in ADAS-cog 11 by tertiles of age groups. RESULTS: Older age at baseline was associated with a slower rate of decline in the ADAS-cog 11 and the Mini-Mental State Examination scores. Almost twice as many subjects aged 80 years and older compared with those aged younger than 70 years would be required to demonstrate a 30% treatment effect on the ADAS-cog 11 in an 18-month AD trial. CONCLUSION: Subject age is an important factor to consider when defining the study population in and analyzing data from AD trials of potential disease-modifying therapies.
Authors: Michael W Weiner; Dallas P Veitch; Paul S Aisen; Laurel A Beckett; Nigel J Cairns; Robert C Green; Danielle Harvey; Clifford R Jack; William Jagust; John C Morris; Ronald C Petersen; Jennifer Salazar; Andrew J Saykin; Leslie M Shaw; Arthur W Toga; John Q Trojanowski Journal: Alzheimers Dement Date: 2016-12-05 Impact factor: 21.566