The Alzheimer's Disease Cooperative Study - Clinical Global Impression of Change (ADCS-CGIC) was modified for use in mild cognitive impairment (MCI) trials and tested in the ADCS MCI randomized clinical trial of donepezil, vitamin E and placebo. We assessed feasibility for its use by determining whether or not: (1) it distinguished a medication effect at 6- and 12- months, (2) baseline demographic or clinical characteristics predicted change, (3) there was an association between MCI-CGIC and change in other clinical measures in order to evaluate external or concurrent validity.
We used a generalized estimating equations approach for ordinal outcome data to test the effects of treatment, baseline characteristics and change in clinical measures on the MCI-CGIC over 12 months, and ordinal logistic regression to assess the association between MCI-CGIC and change in clinical measures at 6 months and 12 months.
On the MCI-CGIC overall, 12.9% and 10.6% were rated as having improved, and 31.6% and 39.8% as having worsened over 6- and 12-months, respectively. The MCI-CGIC did not distinguish the donepezil or vitamin E groups from placebo at 6 and 12 months treatment. Variables at screening or baseline that were associated with worse CGIC scores over 6 and 12 months included white race, greater years of education, worse depression, dementia severity rating, cognitive, and daily activities scores, and lower memory domain scores on a neuropsychological battery. Rate of worsening on the MCI-CGIC over 12 months was associated with change on the AD Assessment Scale-cognitive (ADAS-cog) and on executive function. Worsening at 6 months and 12 months, separately, were associated with the corresponding change in ADAS-cog, ADL, BDI, MMSE, CDR-sb, memory, and executive function.
Change detected by the MCI-CGIC was associated with baseline clinical severity and with change in clinical ratings over 6 and 12 months, supporting the validity of a CGIC approach in MCI. The effect size of the donepezil-placebo difference was similar to that of other outcomes at 12 months. About 40% of MCI patients were judged worse and about 11% improved, consistent with clinical experience and other ratings.