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Effect of cognitive reserve markers on Alzheimer pathologic progression.

ABSTRACT: Education, occupation, premorbid intelligence, and brain size are surrogate markers for cognitive reserve. Whether these markers have biological influence on Alzheimer disease (AD) pathology is not known. We thus aimed to investigate the effect of cognitive reserve proxies on longitudinal change of AD biomarkers. A total of 819 participants with normal cognition, mild cognitive impairment, and mild AD were enrolled in the Alzheimer's Disease Neuroimaging Initiative and followed up with repeated measures of cerebrospinal fluid, positron emission tomography, and magnetic resonance imaging biomarkers. Generalized estimating equations were used to assess whether biomarker rates of change were modified by reserve proxies. Cerebrospinal fluid A?42 decline was slower in normal cognition participants with higher cognitive reserve indexed by education, occupation, and American National Adult Reading Test (ANART). The decline of [F] fluorodeoxyglucose positron emission tomography uptake was slower in AD participants with better performance on the ANART. Education, occupation, and ANART did not modify the rates of magnetic resonance imaging hippocampal atrophy in any group. These findings remained unchanged after accounting for APOE 4, longitudinal missing data, and baseline cognitive performance. Higher levels of reserve markers may slow the rate of amyloid deposition before cognitive impairment and preserve glucose metabolism at the dementia stage over the course of AD pathologic progression.

SUBMITTER: Lo RY

PROVIDER: S-EPMC3745532 | biostudies-literature | 2013 Oct-Dec

REPOSITORIES: biostudies-literature

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Effect of cognitive reserve markers on Alzheimer pathologic progression.

Lo Raymond Y RY Jagust William J WJ

Alzheimer disease and associated disorders 20131001 4

Education, occupation, premorbid intelligence, and brain size are surrogate markers for cognitive reserve. Whether these markers have biological influence on Alzheimer disease (AD) pathology is not known. We thus aimed to investigate the effect of cognitive reserve proxies on longitudinal change of AD biomarkers. A total of 819 participants with normal cognition, mild cognitive impairment, and mild AD were enrolled in the Alzheimer's Disease Neuroimaging Initiative and followed up with repeated ...[more]

PMID: 23552443

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Project description:OBJECTIVE:To investigate the relationship between cognitive reserve (CR) and clinical progression across the Alzheimer disease (AD) spectrum. METHODS:We selected 839 β-amyloid (Aβ)-positive participants with normal cognition (NC, n = 175), mild cognitive impairment (MCI, n = 437), or AD dementia (n = 227) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). CR was quantified using standardized residuals (W scores) from a (covariate-adjusted) linear regression with global cognition (13-item Alzheimer's Disease Assessment Scale-cognitive subscale) 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] 0.22, p < 0.001) and slower decline in memory (β = 0.48, p < 0.001) and executive function (β = 0.67, p < 0.001). Stratified by disease stage, we found similar results for NC (diagnostic conversion: HR 0.30, p = 0.038; ADNI-MEM: β = 0.52, p = 0.028; ADNI-EF: β = 0.42, p = 0.077) and MCI (diagnostic conversion: HR 0.21, p < 0.001; ADNI-MEM: β = 0.43, p = 0.003; ADNI-EF: β = 0.59, p < 0.001), but opposite findings (i.e., more rapid decline) for AD dementia (ADNI-MEM: β = -0.91, p = 0.002; ADNI-EF: β = -0.77, p = 0.081). CONCLUSIONS:Among Aβ-positive individuals, greater CR related to attenuated clinical progression in predementia stages of AD, but accelerated cognitive decline after the onset of dementia.

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Effect of cognitive reserve markers on Alzheimer pathologic progression.

Publications

Effect of cognitive reserve markers on Alzheimer pathologic progression.

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