Abstract
BackgroundThe cognitive reserve (CR) hypothesis presumes higher tolerance of Alzheimer's disease (AD)-related pathology without functional decline for those with high education and more rapid decline after AD onset. Evidence supporting the second part of the hypothesis has been largely confined to U.S.-based studies.ObjectiveTo assess the relationship between education and cognitive decline in a multi-national European cohort of older adults living with AD.MethodsWe analyzed data from participants recruited into the GERAS-EU cohort study from AD clinics in the United Kingdom, Germany, and France. Linear mixed models were employed to assess the relationship between education (dichotomized using a 12-year cutoff) and cognitive decline measured by Mini-Mental State Examination (MMSE) scores during 1.5 to 3 years of follow-up, adjusting for age, sex, time from formal diagnosis, country, comorbidities, and AD treatment.ResultsA total of 1313 participants were analyzed, with mean age of 77.3 years (SD = 7.6), 715 (54.5%) females, and 378 (28.8%) with high education (≥12 years). Participants with high education experienced a 0.19-point greater decline (versus low education group) in MMSE scores every 6 months during follow-up (95% Confidence Interval: 0.03-0.35, p = 0.02). The secondary analyses (stratified by disease severity, sex, or country) showed a consistent direction of the association, although only significant in the severe AD group (p = 0.01).ConclusionsOur findings provide partial support for the CR hypothesis. Delayed AD diagnosis in individuals with high education may contribute to faster decline after diagnosis, highlighting the importance of sensitive screening for early signs of cognitive impairment.