Machine-Learning Assessment of the Predictive Value of Inflammatory Biomarkers for Cognitive Impairment in an Older Hispanic Adult Cohort

Abstract

Small clinical tabular datasets require interpretable machine learning because deep learning is often impractical and ensemble models can be difficult to inspect. A key pitfall is that statistical significance does not necessarily imply predictive utility. Using data from the Panama Aging Research Initiative--Health Disparities (PARI-HD) cohort (n=165), we implemented a leakage-safe threshold-likelihood Bernoulli/Categorical Naive Bayes (BNB/CNB) classifier. Within every training fold, each continuous predictor was reduced to a supervised chi-square-derived state, while income entered the model through a categorical likelihood. All data-dependent steps were performed within repeated stratified 10-fold cross-validation with 30 repeats. The demographic baseline achieved a ROC-AUC of 0.630 +/- 0.017. I-309 (CCL1) was the dominant incremental feature, increasing AUC by 0.110, with paired DeLong tests yielding p<0.05 in 100% of repeats. In the pre-specified primary analysis, I-309 produced a fixed-partition DeLong p=0.0018, with robustness assessed across 200 random partitions, where the median p-value was 0.0011. Within the exploratory family of 18 candidate markers, I-309 achieved a Benjamini-Hochberg-adjusted q=0.032 on the frozen partition and satisfied q<0.05 in 85% of random partitions, whereas no other marker demonstrated reliable incremental predictive value. Because the fitted model is an inspectable table of thresholds and class-conditional probabilities, these results identify I-309/CCL1 as an interpretable candidate feature for tabular prediction of cognitive impairment, pending external validation.