Risk factors and predictive models in the progression from MCI to Alzheimer's disease.

Abstract

Background: The conversion of mild cognitive impairment (MCI) to Alzheimer's disease (AD) is related to various factors. The causal relationships among these factors remain unclear. This study aims to investigate pathways of the progression by using causal analysis and build a predictive model with high accuracy.

Methods: 162 MCI patients were recruited from the Alzheimer's Disease Neuroimaging Initiative database. 68 patients progressed to AD. 94 patients did not convert to AD. We captured standard T1-weighted images, processed them for feature extraction, and selected relevant features using mRMR and LASSO to calculate cortical and nuclear scores. The computational causal structure discovery and regression analyses were adopted to analyze the intricate relationships among APOE ε4 alleles, P-tau, Aβ1-42, cortical and nuclear scores. The individualized prediction nomogram was constructed.

Results: Our results indicated that APOE ε4 alleles was the promoter that caused MCI to transform into AD. Three independent pathways were identified, including P-tau, Aβ1-42, and cortical atrophy. P-tau was the cause of nuclear atrophy. The APOE ε4 alleles, P-tau, Aβ1-42, cortical and nuclear scores all had good predictive value for the MCI conversion. The predictive accuracy of the combined model was the highest, with an AUC of 0.918 in the training cohort and 0.908 in the testing cohort. A multi-predictor nomogram was established.

Conclusion: Our study elucidated the initiating factors and three independent pathways involved in the conversion of MCI to AD. The predictive value of each factor was clarified and a multi-predictor nomogram was established with high accuracy.