Clinical importance in Alzheimer's disease: effects of anchor agreement and disease severity.

OBJECTIVES: Methods of evaluating clinically meaningful decline are critical in research on Alzheimer's disease. A common method of quantifying clinically meaningful change is to calculate an anchor-based minimal clinically important difference (MCID) score. In this approach, individuals who report a meaningful change serve as the "anchors", and the mean level of change for this group serves as the MCID. In research on Alzheimer's disease, there are several possible anchors, including patients, knowledgeable observers (e.g., a family member), and clinicians. The goal of this study was to examine the extent to which agreement among anchors impacts MCID estimation and whether this relationship is moderated by cognitive severity status.

METHODS: Analyses were completed on a longitudinal sample of 2247 adults, aged 50-103, from the Uniform Data Set. Outcome measures included the Montreal Cognitive Assessment, Clinical Dementia Rating-Sum of Boxes, and Functional Activities Questionnaire.

RESULTS: For all of the outcomes, the MCID estimate was significantly higher when meaningful decline was endorsed by all of the anchors compared to when there was disagreement among the anchors. In addition, the MCID estimate was higher with increasing severity of cognitive impairment. Finally, cognitive severity status moderated the influence of agreement among anchors on MCID estimation; as disease severity increased, anchor agreement demonstrated less influence on the MCID.

CONCLUSIONS: MCID estimates based on one anchor may underestimate meaningful change, and researchers should consider the viewpoints of multiple anchors in constructing MCIDs, particularly in the early stages of cognitive decline.