| With the development of more effective pharmacologic agents for treating the symptoms and slowing the progression of Alzheimer's disease (AD), more optimal assessment methods and instruments are needed to evaluate clinical change in AD patients, as well as individuals diagnosed with mild cognitive impairment (MCI) who are at risk for progressive decline to AD. The development of improved outcome measures for AD clinical trials is a major objective of the Alzheimer's Disease Cooperative Study (ADCS), an NIA-sponsored, multi-site clinical trials consortium. The primary goal of the present protocol is to determine the utility, sensitivity, and validity of newly developed or improved assessment instruments designed to evaluate clinical improvement in pharmacologic trials with MCI subjects. The measures will be evaluated in MCI subjects through their inclusion as secondary outcomes in a multi-site clinical trial that will determine whether high doses of vitamin E or Aricept can prevent or delay progression to clinically evident AD. In this separate, parallel protocol, a cohort of normal elderly control subjects will also be evaluated. In both protocols, measures in each of five domains will be evaluated:
(1) cognitive function (tests of delayed verbal memory, concentration, executive function, language function and praxis);
(2) clinical global improvement (Clinical Global Impression of Change [ADCS-CGIC]);
(3) activities of daily living (ADCS-ADL Inventory);
(4) Quality of Life (Logsdon QOL-AD and Cleveland Caregiver QOL Questionnaire), and
(5) pharmaco-economic assessment. Approximately 30 participating ADCS sites and 30 - 50 collaborating sites are conducting a randomized, double-blind, placebo controlled, parallel group clinical trial comparing the effects of vitamin E and Aricept to placebo in slowing the progression from MCI to AD. (See MCI protocol for details).
Including the instruments listed above as secondary outcome measures in the MCI clinical trial will enable us to evaluate the both the utility and pharmacologic sensitivity of the new or improved assessment instruments. Specifically, we will capitalize on the unique expertise, experience, patient resources and staff of the ADCS and collaborating sites to obtain data on validity and longitudinal change for the new assessments.
A total of 720 MCI subjects will be assessed at baseline and every six months for three years as part of the MCI protocol. Separately, 100 normal elderly control subjects will be recruited at selected ADCS sites in order to provide comparison data on the new instruments. These normal subjects will not be involved in the MCI clinical trial, but will receive the same new evaluation instruments repetitively over a three-year period. Both the MCI and normal control study will last 4 years, including time for recruitment (9 months), follow up (3 years), and data analysis (3 months). Following screening and baseline assessments, the normal control subjects will be retested at 12-month intervals to evaluate sensitivity to clinically observable change over time. The Normal Control Protocol will include an evaluation of test-retest reliability for a selected subset of instruments for which test-retest reliability data are not already available. Test-retest reliability will be assessed by means of an additional administration of the subset of instruments at the screening visit, two to four weeks prior to the baseline visit.
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