Informant characteristics are associated with the Clinical Dementia Rating Sum of Boxes scores in the Alzheimer’s Disease patients participating in the National Alzheimer’s Coordinating Center Uniform Data Set

BACKGROUND: The Clinical Dementia Rating Sum of Boxes (CDR-SB) is a widely used measurement score to stage dementia severity; it has become one of the most common outcome measurements in Alzheimer's Disease (AD) research. The CDR-SB requires an informant to provide information to stage a patient's dementia severity. The effect of the informant's characteristics including sex and relationship with patients on the CDR-SB is unknown. We aimed to evaluate the effect of the informant's sex and relationship to the patient on the CDR-SB scores in patients with Alzheimer's Disease with mild cognitive impairment or dementia included in the National Alzheimer's Coordinating Center Uniform Data Set (NACC-UDS). METHOD: We included all participants from the NACC-UDS that had AD as the principal diagnosis, with information about the Mini-Mental State Examination or Montreal Cognitive Assessment scores, and informant sex and relationship to patient; we also analyzed the possible interaction between these characteristics, and the outcome was the CDR-SB. We performed a conditional growth model using multilevel linear regression analysis. RESULT: We included data from 20636 participants, totalling 47727 visits with a median of 2 (1-4) visits. Patients' age at the initial visit was 74.0±9.4 years and 54.1% were females. Informant characteristics were mean 66.2±13.2 years of age, 69.1% were females, and the relationship to patients was 60.5% spouse or partner, 26.7% children and 12.8% other relation. The CDR-SB scores were 0.20 (CI 95%: 0.11 to 0.29) higher when the informant was female. When comparing to informant's relationship with the baseline being spouse or partner, the CDR-SB was 0.39 (CI 95%: 0.25 to 0.53) higher when the informant was the child of the patient and 0.18 (CI 95%: -0.35 to -0.01) lower if other relationship. The only significant interaction was between informant relationships other than spouse or child and female patients where the scores were 0.24 (CI95%: 0.03 to 0.46) higher. CONCLUSION: We found that the CDR-SB scores are significantly modified according to informant characteristics in the NACC-UDS patients with AD diagnosis. These results are clinically relevant because informant characteristics should not affect AD patient staging, and future research should evaluate how to manage these confounding variables.

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