Clinical Manifestations

Abstract

Background: The Uniform Data Set (UDS) neuropsychological battery, administered across Alzheimer's Disease Centers (ADC), includes memory tests but lacks a list-learning paradigm. ADCs often supplement the UDS with their own preferred list-learning task. Given the importance of list-learning for characterizing memory, we aimed to develop a harmonized memory score that incorporates UDS memory tests while allowing centers to contribute differing list-learning tasks.

Method: We applied item-banking confirmatory factor analysis to develop a composite memory score in 5,287 participants (mean age 67.1; SD = 12.2) recruited through 18 ADCs and four consortia (DiverseVCID, MarkVCID, ALLFTD, LEADS) who completed UDS memory tasks (used as linking-items) and one of five list-learning tasks. All analyses used linear regression. We tested whether memory scores were affected by which list-learning task was administered. To assess construct validity, we tested associations of memory scores with demographics, disease severity (CDR Box Score), an independent memory task (TabCAT Favorites, n = 675), and hippocampal volume (n = 811). We compared performances between cognitively unimpaired (n = 279), AD-biomarker+ MCI (n = 26), and AD-biomarker+ dementia (n = 98). In a subsample with amyloid- and tau-PET (n = 49), we compared memory scores from participants with positive vs negative scans determined using established quantitative cutoffs.

Result: Model fit indices were excellent (e.g., CFI = 0.998) and factor loadings were strong (0.43-0.93). Differences in list-learning task had a negligible effect on scores (average Cohen's d = 0.11). Higher memory scores were significantly (p's<.001) correlated with younger age (β = -0.18), lower CDR Box Scores (β = -0.63), female sex (β = 0.12), higher education (β = 0.19), larger hippocampal volume (β = 0.42), and an independent memory task (β = 0.71, p<0.001). The memory composite declined in a stepwise fashion by diagnosis (cognitively unimpaired>MCI>AD dementia, p<0.001). On average, amyloid-PET positivity was associated with lower composite scores, but was not statistically significant (β = -0.34; p = 0.25; d = 0.40). Tau-PET positivity was associated with worse performance, demonstrating a large effect size (β = -0.75; p<0.002; d = 0.91).

Conclusion: The harmonized memory score developed in a large national sample was stable regardless of contributing list-learning task and its validity for cross-cohort ADRD research is supported by expected associations with demographics, clinical measures, and Alzheimer's biomarkers. A processing script will be made available to enhance cross-cohort ADRD research.