To determine if the addition of delayed recall (DR) assessment adds sensitivity to the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-cog) in clinical trials in mild cognitive impairment (MCI) and Alzheimer Disease (AD).
Memory, particularly DR, is the most sensitive test for early detection of AD and MCI. However, it is not clear that assessment of DR adds benefit for measuring change over time after a diagnosis is made or in clinical trials. The ADAS-cog is the most commonly used tool to assess treatment efficacy in AD clinical trials. In an attempt to improve sensitivity to change, assessment of DR after the 3-trial, 10-word list was added to the standard 11-item ADAS-cog. We examined the added value of the DR in participants with MCI and AD followed for at least 1 year.
Data from 111 subjects with AD and 259 subjects with MCI who were randomly assigned to the placebo arm of 2 clinical trials were included. Participants with AD had Mini-Mental State Examination scores of 13 to 27 and those with MCI had 24 to 30. We calculated the ADAS-cog11 score based on the original 11 items (range: best to worse, 0 to 70), the DR item score (range: 0 to 10 words not recalled), and the ADAS-cog12 (range: 0 to 80). We assessed the rate of missing items for DR over time, the change scores, the association between scores and baseline performance, and used longitudinal mixed effects regression models to examine the rate of change.
At baseline AD subjects were near floor on DR (8.93±1.6 SD) and showed little change over 1 year (0.12±1.34); the MCI subjects baseline DR was 6.2±2.2 with 1-year change of 0.20±1.7. We compared standardized change (change/SD) for ADAS-cog11, and 12 in MCI and found a 10% improvement with ADAS-cog12; there was no improvement in the AD group. In a subset of MCI and AD cases with matching Mini-Mental State Examination (23 to 27), the ADAS-cog12 provided an 18% improvement in standardized change in MCI subjects, with no benefit in the AD cohort, primarily owing to increased variance.
The addition of DR to the ADAS-cog score increased the ability to detect change in subjects with MCI over 1 year compared with the ADAS-cog11 but increased the variance in subjects with AD, even in those with mild impairment These findings speak to the need to tailor outcome measures to the specific study population and diagnosis for maximal efficiency and economy when conducting clinical trials.
*Department of Psychiatry, Mount Sinai School of Medicine
†James J Peters VAMC, Bronx, NY
‡Departments of Family and Preventive Medicine and Neurosciences
§Alzheimer's Disease Research Center
**Department of Neurosciences, UCSD, La Jolla
¶Departments of Psychiatry and Neurology, University Southern California Keck School of Medicine, Los Angeles, CA
∥Department of Neurology, Mayo Clinic, Rochester MN
Supported by the following NIA grants: U01AG10483 and AG005138, P50 AG05142, and California Alzheimer Disease Center Program.
Reprints: Mary Sano, PhD, James J Peters VAMC, 130 W. Kingsbridge Road, Code 150 Room 1F01, Bronx, NY 10468 (e-mail: Mary.email@example.com).
Received October 24, 2009
Accepted February 24, 2010