A multicenter evaluation of new treatment efficacy instruments for Alzheimer's disease clinical trials: overview and general results. The Alzheimer's Disease Cooperative Study.
ABSTRACT Evaluating treatment efficacy in Alzheimer's disease (AD) clinical trials requires optimal assessment methods to determine the extent and clinical meaningfulness of potential therapeutic effects of pharmacologic agents. Development of improved outcome measures for AD clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multisite clinical trials consortium. The ADCS Instrument Development Project evaluated the sensitivity, reliability and validity of new or improved measures in each of five assessment domains: (a) cognition (immediate and delayed memory, praxis, attention, and executive function); (b) clinical global change; (c) activities of daily living; (d) behavioral symptoms (agitation and other noncognitive symptoms); and (e) cognition in severely impaired patients. A total of 306 English-speaking subjects were enrolled in the study, including AD patients stratified by disease severity and cognitively normal, age-matched elderly subjects. Half were retested at 1 month and 2 months after baseline, and all received 6- and 12-month follow-up assessments. Spanish versions of these new measures are currently being evaluated. The development of this multisite study, the common methods and procedures, and a detailed description of the cohort are provided in this overview article. This multisite project demonstrates the feasibility of a consortium approach to instrument development. We were able to develop new instruments and efficiently evaluate their reliability and sensitivity to longitudinal change by capitalizing on the experience and patient resources of the participating ADCS research sites.
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ABSTRACT: ABSTRACT Background: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) set of tests is frequently used for tracking cognition longitudinally in both clinical and research settings. Repeated cognitive assessments are an important component in measuring such changes; however, practice effects and attrition bias may obscure significant clinical change over time. The current study sought to examine the presence and magnitude of practice effects and the role of attrition bias in a sample of cognitively normal older men enrolled in a prevention trial. Method: Participants were grouped according to whether they completed five years of follow-up (n = 182) or less (n = 126). Practice effects were examined in these participants as a whole (n = 308) and by group. Results: Findings indicate that moderate practice effects exist in both groups on the CERAD T-score and that attrition bias likely does not play a contributing role in improved scores over time. Conclusion: The current study provides additional evidence and support for previous findings that repeated cognitive assessment results in rising test scores in longitudinally collected data and demonstrates that these findings are unlikely to be due to attrition.International Psychogeriatrics 04/2013; · 1.89 Impact Factor
Article: GalantamineDrugs 01/2000; 60(5). · 4.13 Impact Factor
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ABSTRACT: The Severe Impairment Battery (SIB), a reliable cognitive measure for evaluating treatment response in advanced Alzheimer's disease (AD), takes approximately 20 min to administer. A recently derived 8-item version of the SIB - the SIB-8 - which takes about 3 min to administer, may represent a more convenient tool for use in clinical practice. The current analyses further explored the SIB-8 scale with respect to its validity and sensitivity. A post hoc analysis was performed using data from a 24-week trial of donepezil 23 mg/day and 10 mg/day in > 1400 patients with moderate to severe AD [baseline Mini-Mental State Examination (MMSE) score 0-20]. Treatment effects on cognition (patterns of score change) were assessed using the full SIB and SIB-8 in the total study population and subgroups based on concomitant memantine use and baseline MMSE. Internal consistency/agreement and correlations between the SIB and SIB-8 and other clinical end points were evaluated. Assessment of score changes from baseline to week 24 with donepezil (23 or 10 mg/day) demonstrated comparable patterns of change when using the SIB-8 and the full SIB, despite inherent differences in the total score ranges for the two scales. Internal consistency/agreement between the full SIB and SIB-8 was good (Cronbach's alphas: 0.77-0.95). SIB-8 scores reliably correlated with SIB total scores (r = 0.859, baseline; r = 0.900, week 24; p < 0.0001), as well as MMSE scores (r = 0.7163, baseline; r = 0.7963, week 24; p < 0.0001). Scores on both SIB scales were moderately associated with functional measures at baseline and week 24. In this post hoc analysis, similar treatment effects were measured by the full SIB and the SIB-8. Very good internal consistency/agreement and strong correlations between the SIB and the more rapid and convenient SIB-8 indicate that the SIB-8 may be a useful and efficient clinical proxy for the full SIB in evaluating treatment response in patients with advanced AD.International Journal of Clinical Practice 10/2013; 67(10):1050-6. · 2.54 Impact Factor