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<.001)
and slower decline in memory (β=.48, p<.001) and executive
functions (β=.67, p<.001). Stratified by disease stage, we found
similar results for NC (diagnostic conversion: HR=.30, p=.038; ADNI-MEM:
β=.52, p=.028; ADNI-EF: β=.42, p=.077) and MCI (diagnostic conversion:
HR=.21, p<.001; ADNI-MEM: β=.43, p=.003; ADNI-EF: β=.59,
p<.001), but opposite findings (i.e. more rapid decline) for AD
dementia (ADNI-MEM: β=-.91, p=.002; ADNI-EF: β=-.77, p=.081). Conclusions:
Among Aβ-positive individuals, greater CR related to attenuated clinical
progression in pre-dementia stages of AD, but accelerated cognitive
decline after the onset of dementia.