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This study aims to analyse hyperechoic substantia nigra (HSN) characteristics and the correlation of HSN with clinical features and blood biomarkers in patients with Parkinson's disease (PD). Transcranial sonography (TCS) evaluations of the substantia nigra (SN) were performed in 40 healthy controls and 71 patients with PD, including patients with SN hyperechogenicity (SN+) and those with normal SN echogenicity (SN−). Evaluation of motor and non‐motor symptoms was assessed by a series of rating scales. The uricase method was used to determine serum uric acid (UA) levels, and enzyme‐linked immunosorbent assay (ELISA) was used to measure plasma interleukin (IL)‐1β levels. TCS showed 92.50% specificity and 61.97% sensitivity in differentiating PD patients from controls. The area of SN+ contralateral to the side of initial motor symptoms (SNcontra) was larger than that ipsilateral to the side of initial motor symptoms (SNipsi). The PDSN+ group had lower Argentine Hyposmia Rating Scale (AHRS) scores and UA levels than the PDSN− group. Binary logistic regression analysis revealed that AHRS scores and UA levels could be independent predictors for HSN. The larger SN echogenic area (SNL) sizes positively correlated with plasma IL‐1β levels in PD patients with SN+. The present study provides further evidence of the potential of SN echogenicity as an imaging biomarker for PD diagnosis. PD patients with HSN have more severe non‐motor symptoms of hyposmia. HSN in PD patients is related to the mechanism of abnormal iron metabolism and microglial activation. [ABSTRACT FROM AUTHOR]

• This study showed that in Chinese PD patients, old age, low education level, female sex, and severe motor symptoms were risk factors for cognitive impairment. • Decreased UCH-L1 levels and elevated NfL levels in the blood were related to cognitive decline in PD patients; additionally, this study is the first to report a negative correlation between UCH-L1 and NfL levels. • We found that UCH-L1 and NfL levels had high sensitivity and specificity in the diagnosis of cognitive impairment in Parkinson's disease, especially UCHL1 levels. • These proteins are promising biomarkers for diagnosing cognitive impairment in Parkinson's disease. Ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and Neurofilament light chain (NfL) are associated with Lewy body formation, Lewy bodies are the main pathological feature of Parkinson's disease (PD). The relationship between UCH-L1 and PD cognition remains unclear, and NfL is an important marker of cognitive impairment. The aim of this study is to investigate the relationship among serum UCH-L1 levels, plasma NfL levels and cognitive dysfunction in PD patients. There were significant differences in UCH-L1 and NfL levels among PD patients with normal cognitive function (PD-CN), PD patients with mild cognitive impairment (PD-MCI), and PD-dementia patients (PDD) (P < 0.001; P < 0.001). The PDD group had lower levels of UCH-L1 (Z = 6.721, P < 0.001; Z = 7.577, P < 0.001) and higher levels of NfL (Z = −3.626, P = 0.001; Z = −2.616P = 0.027) than the PD-NC and PD-MCI groups. Serum UCH-L1 levels were positively correlated with MMSE scores, MoCA scores, and its subitems in PD patients (P < 0.001), and plasma NfL levels were negatively correlated with MMSE scores, MoCA scores, and its items (P < 0.01) (except for "abstract"). Decreased UCH-L1 levels and elevated NfL levels in the blood are associated with cognitive dysfunction in PD; thus, these proteins are potential biomarkers for the diagnosis of cognitive dysfunction in PD patients. [ABSTRACT FROM AUTHOR]