Inverse association between CSF Aβ 42 levels and years of education in mild form of Alzheimer's disease: the cognitive reserve theory.

In Alzheimer's disease (AD), the cognitive reserve theory predicts that at any level of assessed clinical severity, the underlying brain pathology is more advanced in patients with more cognitive reserve. Recent evidences suggest that cerebrospinal fluid (CSF) biomarkers may reflect the brain pathology in AD. We investigated the relationship between education level and CSF concentrations of β-amyloid, total tau and phosphorylated tau (ptau-181) in a cohort of 70 subjects newly diagnosed with AD. We report that CSF concentration of β-amyloid was inversely associated with years of education, after adjustment for age, sex, and severity of the disease. We further demonstrate in stratified analysis that this relation was mainly present in mild form of the disease (CDR1), and was attenuated in more advanced forms of the disease. These results are consistent with the cognitive reserve theory, and suggest that cognitive reserve may be protective against amyloid related cognitive impairment at the onset of the clinical dementia.