Data from: Cognitive reserve and clinical progression in Alzheimer's disease: a paradoxical relationship

Objective: To investigate the relationship between cognitive reserve (CR) and clinical progression across the Alzheimer's disease (AD) spectrum. Methods: We selected 839 Aβ-positive subjects with normal cognition (NC, n=175), mild cognitive impairment (MCI, n=437) or AD dementia (n=227) from the Alzheimer's Disease Neuroimaging Initiative. CR was quantified using standardized residuals (W-scores) from a (covariate-adjusted) linear regression with global cognition (ADAS-Cog 13) as an independent variable-of-interest, and either gray matter volumes or white matter hyperintensity volume as dependent variables. These W-scores, reflecting whether an individual's degree of cerebral damage is lower or higher than clinically expected, were tested as predictors of diagnostic conversion (i.e. NC to MCI/AD dementia, or MCI to AD dementia) and longitudinal changes in memory (ADNI-MEM) and executive functions (ADNI-EF). Results: The median follow-up period was 24 months (interquartile range: 6-42). Corrected for age, sex, APOE4-status and baseline cerebral damage, higher gray matter volume-based W-scores (i.e. greater CR) were associated with a lower diagnostic conversion risk (hazard ratio [HR]= .22, p