Disease progression modeling of Alzheimer’s disease according to education level
Abstract Background To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to dementia and to investigate the effect of education level on the whole disease spectrum. Methods We enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB) score. Three cohorts, SCI (n=85), amnestic mild cognitive impairment (AMCI, n=240), and AD dementia (ADD, n=240), were overlapped in two consecutive cohorts (SCI and AMCI, AMCI and ADD) to construct a model of disease course, and a model with multiple single-cohorts was estimated using a mixed-effect model. To examine the effect of education level on disease progression, the disease progression model was developed with data from lower (≤12) and higher (>12) education groups. Results Disease progression takes 277.0 months (23.1 years) to advance from 0 to 18 points using the CDR-SB score. Based on our predictive equation, it takes 101.9 months to progress from SCI to AMCI and 71.1 months to progress from AMCI to ADD. The rate of CDR-SB progression was different according to education level. The lower-education group showed faster CDR-SB progression from SCI to AMCI compared to the higher-education group, and this trend disappeared from AMCI to ADD. Conclusion In the present study, we developed a disease progression model of AD spectrum from preclinical to the end stage of the disease. Our findings suggest that the contribution of education to cognitive decline varies depending on disease stage.