Prospective study in 184 PD patients produced a classifier combining substantia nigra hyperechogenicity (SNH), CRP, and homocysteine to distinguish PD cognitive stages (AUCs 0.729–0.823) and identified SNH, elevated CRP and Hcy as independent risk factors for cognitive impairment.

Moderate therapeutic relevance: the work links noninvasive imaging (SNH) with inflammation and homocysteine pathways, offering a stratification tool for trials and pointing to actionable avenues (anti‑inflammatory, Hcy‑lowering, iron‑modulating strategies), though it remains a…

BACKGROUND: Cognitive impairment (CI) is recognized as a debilitating complication of Parkinson's disease (PD). This study was designed to develop a diagnostic classification model by integrating substantia nigra hyperechogenicity (SNH) and inflammationassociated biomarkers to evaluate its diagnostic performance in distinguishing PD CI stages. METHODS: Between January, 2023 and May, 2024, 184 patients with PD who underwent transcranial sonography were prospectively enrolled. Based on Montreal Cognitive Assessment (MoCA) scores, participants were categorized into three groups: cognitive impairment (PD-CI, MoCA <26), mild cognitive impairment (PD-MCI, MoCA 22-25), and dementia (PD-dementia, MoCA ≤21). Ultrasound features and inflammationassociated biomarkers were screened with univariate analyses. Multivariate logistic regression was used to identify independent diagnostic factors, and receiver operating characteristic (ROC) curve analysis was used to assess model discrimination. RESULTS: Multivariate regression analysis indicated that age <50 years and more years of education were significantly associated factors for CI (OR = 0.170, p = 0.0350; OR = 0.8780, p = 0.0020, respectively), whereas Unified Parkinson's Disease Rating Scale Part III (UPDRSIII) score (OR = 1.024, p = 0.0270), SNH (OR = 2.550, p = 0.0030), elevated C-reactive protein (CRP) (OR = 2.038, p = 0.0350), and elevated homocysteine (Hcy) (OR = 2.830, p = 0.0020) were independent risk factors. The area uinder the curves (AUCs) for the combined SNH+CRP+Hcy model in predicting PD-CI, PD-MCI, and PD-dementia were 0.783, 0.729, and 0.823, respectively; these values were significantly superior to those for single or dual marker combinations (p < 0.05), with the strongest performance for distinguishing PD-dementia. CONCLUSION: An SNH and inflammationassociated biomarkerbased model was developed for predicting the stage of cognitive impairment in PD. Clinical targets for individualized intervention can be provided, and clinical risk stratification and care pathways can be optimized. Furthermore, the model supports the iron deposition-neuroinflammation-CI pathway hypothesis, providing a mechanistic rationale for ultrasoundbased PD-CI diagnosis.