Screening and predicting progression from high-risk mild cognitive impairment to Alzheimer’s disease

Abstract

Individuals with mild cognitive impairment (MCI) are clinically heterogeneous, with different risks of progression to Alzheimer's disease. Regular follow-up and examination may be time-consuming and costly, especially for MRI and PET. Therefore, it is necessary to identify a more precise MRI population. In this study, a two-stage screening frame was proposed for evaluating the predictive utility of additional MRI measurements among high-risk MCI subjects. In the first stage, the K-means cluster was performed for trajectory-template based on two clinical assessments. In the second stage, high-risk individuals were filtered out and imputed into prognosis models with varying strategies. As a result, the ADAS-13 was more sensitive for filtering out high-risk individuals among patients with MCI. The optimal model included a change rate of clinical assessments and three neuroimaging measurements and was significantly associated with a net reclassification improvement (NRI) of 0.246 (95% CI 0.021, 0.848) and integrated discrimination improvement (IDI) of 0.090 (95% CI - 0.062, 0.170). The ADAS-13 longitudinal models had the best discrimination performance (Optimism-corrected concordance index = 0.830), as validated by the bootstrap method. Considering the limited medical and financial resources, our findings recommend follow-up MRI examination 1 year after identification for high-risk individuals, while regular clinical assessments for low-risk individuals.