Supplementary Material for: Association of lifelong cognitive reserve with dementia and mild cognitive impairment among older adults with limited formal education: a population-based cohort study

Introduction: Early-life educational attainment contributes to cognitive reserve (CR). We investigated the associations of lifelong CR with dementia and mild cognitive impairment (MCI) among older people with limited formal education. Methods: This population-based cohort study included 2127 dementia-free participants (≥60 years; 59.4% women; 81.5% with no or elementary school) who were examined at baseline (August-December 2014) and follow-up (March-September 2018). Lifelong CR score at baseline was generated from six lifespan intellectual factors. Dementia, MCI, and their subtypes were defined according to the international criteria. Data were analyzed using Cox proportional-hazards models. Results: During the total of 8330.6 person-years of follow-up, 101 persons were diagnosed with dementia, including 74 with AD and 26 with VaD. The high (versus low) tertile of lifelong CR score was associated with multivariable-adjusted hazards ratio (95% confidence interval) of 0.28 (0.14–0.55) for dementia and 0.18 (0.07–0.48) for AD. The association between higher CR and reduced AD risk was significant in people aged 60-74 but not in those aged≥75 years (P-for-interaction=0.011). Similarly, among MCI-free people at baseline (n=1635), the high (versus low) tertile of lifelong CR score was associated with multivariable-adjusted hazard ratio of 0.51 (0.38–0.69) for MCI and 0.46 (0.33–0.64) for amnestic MCI. Lifelong CR was not related to VaD or non-amnestic MCI. Discussion: High lifelong CR is associated with reduced risks of dementia and MCI, especially AD and amnestic MCI. It highlights the importance of lifelong CR in in maintaining late-life cognitive health even among people with no or limited education.