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

Authors

  • Kenneth Rockwood,

    Corresponding author
    1. Division of Geriatric Medicine, Capital District Health Authority, Dalhousie University, Halifax, NS, Canada
    2. Geriatric Medicine Research Unit, Capital District Health Authority, Dalhousie University, Halifax, NS, Canada
    • Division of Geriatric Medicine, Dalhousie University, 1421-5955 Veterans' Memorial Lane, Halifax, NS, B3H 2E1 Canada.
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  • Sherri Fay,

    1. Division of Geriatric Medicine, Capital District Health Authority, Dalhousie University, Halifax, NS, Canada
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  • Mary Gorman

    1. St. Martha's Hospital, Antigonish, NS, Canada
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  • Kenneth Rockwood has received ad hoc consulting or speaker honoraria from Janssen-Ortho, the study's co-sponsor, Glaxo Smith Kline, Lundbeck, Merck, Myriad, Novartis, Numico, Pfizer and Shire. He has no stock ownership in pharmaceutical companies. He also established DementiaGuide Inc., which promotes symptom-based assessments of the response to treatment for dementia. Sherri Fay and Mary Gorman declare no competing interests.

Abstract

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 ≥ 4 points on the ADAS-cog at 6 months, and 16/99 showed ≥ 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. Copyright © 2009 John Wiley & Sons, Ltd.

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