Screening strategies and dynamic risk prediction models for Alzheimer's disease

Characterizing the progression from Mild cognitive impairment (MCI) to Alzheimer's disease (AD) is essential for early AD prevention and targeted intervention. Our goal was to construct precise screening schemes for individuals with different risk of AD and to establish prognosis models for them.

We constructed a retrospective cohort by reviewing individuals with baseline diagnosis of MCI and at least one follow-up visits between November 2005 and May 2021. They were stratified into high-risk and low-risk groups with longitudinal cognitive trajectory. Then, we established a screening framework and obtained optimal screening strategies for two risk groups. Cox and random survival forest (RSF) models were developed for dynamic prognosis prediction.

In terms of screening strategies, the combination of Clinical Dementia Rating Sum of Boxes (CDRSB) and hippocampus volume was recommended for the high-risk MCI group, while the combination of Alzheimer's Disease Assessment Scale Cognitive 13 items (ADAS13) and FAQ was recommended for low-risk MCI group. The concordance index (C-index) of the Cox model for the high-risk group was 0.844 (95% CI: 0.815-0.873) and adjustments for demographic information and APOE ε4. The RSF model incorporating longitudinal ADAS13, FAQ, and demographic information and APOE ε4 performed for the low-risk group.

This precise screening scheme will optimize allocation of medical resources and reduce the economic burden on individuals with low risk of MCI. Moreover, dynamic prognosis models may be helpful for early identification of individuals at risk and clinical decisions, which will promote the secondary prevention of AD.