164、PL-PD:帕金森病代谢—炎症状态交互与运动功能进展的纵向计算研究( PL-PD: Longitudinal Computational Investigation of Metabolic–Inflammatory State Interactions and Motor Progression in Parkinson's Disease)

Motor progression in Parkinson’s disease (PD) is primarily assessed using MDS-UPDRS Part III, yet its individual-level predictive capacity at the 12-month horizon is limited; conventional clinical variables (age, disease duration, Hoehn–Yahr stage, baseline motor score, levodopa equivalent daily dose) explain only a fraction of the variance in motor outcomes. Glycaemic dysregulation and peripheral systemic inflammation occupy candidate mechanistic positions in PD pathophysiology, but their incremental predictive value beyond routine clinical variables has not been tested within a pre-specified, falsifiable framework. Prim-Lex Medicine posits the Animal-Life Prim-Fire—anchored in the NADH/NAD⁺ redox couple and glycolytic–oxidative phosphorylation coupling—as the only Prim-Fire level directly relevant to PD clinical questions; however, its direct measurements (NAD(P)H FLIM, lactate/pyruvate ratio, mitochondrial function assays) are inaccessible in general neurology clinics, creating a methodological tension between theoretical clarity and clinical measurability. This paper develops the PL-PD Framework. Its core methodological shift is explicit: rather than “measuring the Prim-Fire” in general hospitals, the framework tests whether the Prim-Fire level has left reproducible motor-outcome predictive traces—independent of conventional PD clinical variables—in routinely available haematological and clinical data. The detection layer comprises four core groups of information: MDS-UPDRS Part III, standard clinical data (age, sex, disease duration, Hoehn–Yahr stage, LEDD), metabolic indices (fasting plasma glucose [FPG], HbA1c), and inflammatory indices (SIRI derived from complete blood count, hs-CRP). The computation layer simplifies the Five-Element structure into two candidate modules: Fire (), an equal-weight aggregation of standardized FPG and HbA1c, positioned as a joint candidate proxy for host glycaemic burden; and Wood (), an equal-weight aggregation of standardized log SIRI and log(1+hs-CRP), positioned as a joint candidate proxy for peripheral systemic inflammatory burden. The Fire–Wood interaction is the sole coupling structure entering formal testing. Three substantive methodological revisions are made to the prior framework. First, the primary outcome is frozen as the MDS-UPDRS Part III total score at month 12 (with baseline-adjusted follow-up score as the primary analysis and change score as sensitivity analysis), rather than simultaneously suspending diagnostic, severity, treatment-response, and multimodal biomarker outcomes. Second, a five-tier model comparison hierarchy is established: (clinical baseline: baseline MDS-UPDRS III, age, sex, disease duration, Hoehn–Yahr, LEDD), , , (baseline + four standardized raw variables: FPG, HbA1c, log SIRI, log(1+hs-CRP)), and ; the comparison of versus is the critical contrast for judging whether equal-weight aggregation confers parsimony advantages. Third, H1 is judged primarily by on the validation set; MAE, calibration (intercept/slope/plot), and predictive serve as supporting evidence; DCA does not enter the H1 judgment for the continuous primary outcome and is used only for exploratory analysis of the binary secondary outcome when a pre-specified, clinically defensible decision scenario exists. The framework explicitly states that FPG, HbA1c, SIRI, and hs-CRP are not direct measures of NADH/NAD⁺ or central neuroinflammation; that a statistically significant Fire–Wood interaction does not constitute proof of Five-Element generative or restrictive biological mechanisms; and that PL-PD scores must not replace MDS clinical diagnostic criteria, levodopa dose adjustment, DBS indication judgment, or clinical decision-making. Its anticipated contribution is strictly limited: a minimum viable clinical validation version executable in secondary and tertiary hospital neurology departments, with actually collectable data and honestly falsifiable hypotheses.