Abstract

To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to the end stage of AD dementia (ADD) and to investigate the effect of education level on the whole disease spectrum, we enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB). Three cohorts, SCI (n = 85), amnestic mild cognitive impairment (AMCI, n = 240), and 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. Disease progression takes 274.3 months (22.9 years) to advance from 0 to 18 points using the CDR-SB. Based on our predictive equation, it takes 116.5 months to progress from SCI to AMCI and 56.2 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. In the present study, we developed a disease progression model of AD spectrum from SCI to the end stage of ADD. Our disease modeling provides us with more understanding of the effect of education on cognitive trajectories.

Highlights

  • To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to the end stage of AD dementia (ADD) and to investigate the effect of education level on the whole disease spectrum, we enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB)

  • Our original analysis produced a model that, when nondecliners were included, showed a consistent progression pattern where the lower-education group demonstrated a faster CDR-SB progression from SCI to amnestic mild cognitive impairment (AMCI) than the higher-education group, and this trend disappeared from AMCI to ADD (Supplementary table 3, Supplementary figures 1 and 2)

  • Based on the predictive equation, it takes 274.3 months to increase the CDR-SB value from 0 to 18 points. We found that it takes 116.5 months to progress from SCI to AMCI and 56.2 months to progress from AMCI to ADD

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Summary

Introduction

To develop a disease progression model of Alzheimer’s disease (AD) that shows cognitive decline from subjective cognitive impairments (SCI) to the end stage of AD dementia (ADD) and to investigate the effect of education level on the whole disease spectrum, we enrolled 565 patients who were followed up more than three times and had a clinical dementia rating sum of boxes (CDR-SB). We developed a disease progression model of AD spectrum from SCI to the end stage of ADD. A few studies have followed participants with normal cognition at baseline to ADD, such studies are difficult because it can take several decades to develop dementia.

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