The ADAS-cog and clinically meaningful change in the VISTA clinical trial of galantamine for Alzheimer's disease.

BACKGROUND A minimum 4-point change at 6 months on the Alzheimer's disease assessment scale-cognitive subscale (ADAS-cog) is deemed clinically important, but this cut-point has been little studied in relation to clinical meaningfulness. In an investigator-initiated, clinical trial of galantamine, we investigated the extent to which a 4-point change classifies goal attainment by individual patients. METHODS Secondary analysis of the video imaging synthesis of treating Alzheimer's disease (VISTA) study: a 4-month, multi-centre, parallel-group, double-blind, placebo-controlled, trial of galantamine in 130 mild-moderate Alzheimer's disease patients (4-month open-label follow-up). ADAS-cog responses at 6 months were compared with outcomes on three clinical measures: clinician's interview based impression of change-plus caregiver input (CIBIC+), patient/carer-goal attainment scaling (PGAS) and clinician-GAS (CGAS). RESULTS Thirty-seven of 99 patients improved by > or = 4 points on the ADAS-cog at 6 months, and 16/99 showed > or = 4-point worsening. ADAS-cog change scores correlated notionally to modestly with changes on the CGAS (r = -0.31), the PGAS (r = -0.29) and the CIBIC+ (r = 0.31). As a group, patients with ADAS-cog improvement were significantly more likely to improve on the clinical measures; those who worsened showed non-significant clinical decline. Individually, about half were misclassified in relation to each clinical measure; often when the ADAS-Cog detected 'no change', clinically meaningful effects could be detected. Even so, no ADAS-Cog cut-point optimally classified patients' clinical responses. CONCLUSION A 4-point ADAS-cog change at 6 months is clinically meaningful for groups. Substantial individual misclassification between the ADAS-cog and clinical measures suggests no inherent meaning to a 4-point ADAS-cog change for a given patient.