Title : The CI-HI & CICR-HI: Development and validation of patient and caregiver-reported outcome measures for Alzheimer’s disease, mild cognitive impairment, and Dementia
Abstract:
Background: As new therapies are developed across the Alzheimer’s disease (AD) continuum, it is critical that patient and caregiver-reported changes in symptomatic health are incorporated into clinical trials. The US FDA encourages the use of patient and observer-reported outcome measures to evaluate the therapeutic benefits of potential new treatments in AD, mild cognitive impairment (MCI), and dementia. Here, we outline the development and validation of The Cognitive Impairment-Health Index (CI-HI) and The Cognitive Impairment Caregiver Reported-Health Index (CICR-HI), two novel instruments developed and validated using large-scale data from patients and caregivers, which measure multifactorial disease burden in the symptomatic domains of greatest importance to patients.
Methods: We conducted qualitative interviews and two large cross-sectional studies involving individuals with AD, MCI, or dementia and caregivers of individuals with AD, MCI, or dementia to ascertain the prevalence and impact of symptoms. We selected questions for the CI-HI and CICR-HI based on their relevance and potential responsiveness to therapeutic intervention. We performed an initial analysis of internal consistency, beta testing, test-retest reliability assessments, and known groups testing to generate instrument subscales and to optimize instrument clarity, usability, meaningfulness, responsiveness, and reliability. Lastly, we performed a final internal consistency and area under the curve analyses of the CI-HI and CICR-HI.
Results: Fifteen individuals with AD, MCI, or dementia and fifteen caregivers of individuals with AD, MCI, or dementia participated in qualitative interviews to determine the most prevalent and impactful symptoms. The symptoms of greatest prevalence and impact were used to construct cross-sectional surveys, completed by 104 individuals with AD, MCI, or dementia and 329 caregivers of individuals with AD, MCI or dementia. We found through validation testing that the CI-HI and CICR-HI are highly relevant, reliable, and capable of distinguishing between groups based upon varied demographic and clinical characteristics. The CI-HI encompasses nine independently validated subscales: (1) Memory; (2) Cognition; (3) Fatigue; (4) Sleep or Daytime Sleepiness; (5) Social Satisfaction; (6) Communication; (7) Emotional Health; (8) Activity Participation; and (9) Pain. The CICR-HI captures observable aspects of disease burden in AD, MCI, and dementia and mirrors the subscale domains of the CI-HI except for the Pain subscale, which is not included in the CICR-HI. Collectively, these instruments measure multifactorial disease burden across the cognitive impairment spectrum.
Conclusion: The Cognitive Impairment-Health Indices are validated and designed to quantify changes in the multifactorial symptomatic burden in individuals with AD, MCI, and dementia over time and in response to therapeutic intervention during clinical trials.
