ABSTRACT
Background: Soluble fragment of triggering receptor expressed on myeloid cells 2 (sTREM2) in cerebrospinal fluid (CSF) is a biomarker of microglial activation and increased in several neurodegenerative diseases. However, the role of sTREM2 in Parkinson's diseases (PDs) remains unclear. This study aims to investigate whether CSF sTREM2 is changed during the pathology of PD and its association with cognitive decline. Methods: We recruited 219 de novo patients with PD and 100 healthy controls from Parkinson's Progression Markers Initiative (PPMI). Cross-sectional and longitudinal associations between cognition and CSF sTREM2 were evaluated using multivariable-adjusted models. To assess the changes in CSF sTREM2 during the pathology of PD, patients were classified through the A/T classification framework with addition of α-synuclein (α-syn), which we implemented based on the CSF amyloid ß-peptide 1-42 (A) and phosphorylated tau (T) and α-syn (S). Results: The CSF sTREM2 did not differ between healthy controls and patients with PD or between PD clinical subgroups (p > 0.05). However, higher baseline CSF sTREM2 predicted greater global cognitive decline in patients with PD (ß = -0.585, p = 0.039). Moreover, after a mean follow-up of 5.51 ± 1.31 years, baseline CSF sTREM2 that elevated in the middle tertile (HR = 2.426, 95% CI: 1.023-5.754, p = 0.044) and highest tertile (HR = 2.833, 95% CI: 1.226-6.547, p = 0.015) were associated with a future high risk of cognitive decline. Additionally, CSF sTREM2 decreased in abnormal Aß pathology (A+) and α-syn pathology (S+) but normal tau pathology, while increased in abnormal phosphorylated tau (T+) (p < 0.05). Conclusion: CSF sTREM2 may be a promising predictor for the cognitive decline in PD rather than a diagnostic biomarker. The dynamic change in CSF sTREM2 in PD may help to the monitor of neuronal injury and microglial activity.
ABSTRACT
BACKGROUND This study aimed to investigate the risk factors and patterns of cerebral microbleeds (CMBs) in Parkinson disease (PD) and the impact of CMBs on cognitive function and quality of life (QoL). MATERIAL AND METHODS Patients with PD that underwent susceptibility-weighted imaging were recruited and divided into CMB-free, lobar-CMB, deep-CMB, and mixed-CMB groups according to CMB location. Motor function (MDS-UPDRS III), cognitive abilities (MoCA, MMSE), and QoL (PDQ-39) were compared among groups. The risk factors for CMBs in patients with PD and the association between CMBs and cognition and QoL were analyzed using multivariable logistic regression models and linear regression models. RESULTS Among the 209 patients with PD, 42 (20.1%) had CMBs. Lobar, deep, and mixed CMBs were observed in 15 (35.7%), 17 (40.5%), and 10 (23.8%) patients, respectively. A higher frequency of hypertension was independently associated with deep CMBs (odds ratio [OR]=4.379, 95% CI: 1.405-13.643, P=0.011). The deep-CMB and mixed-CMB groups had lower MoCA scores and MMSE scores than the CMB-free group, especially in domains of naming, attention, and orientation (P<0.05). Additionally, the presence of CMBs was associated with lower MMSE (R²=0.140, ß=-0.301, P<0.001) and MoCA (R²=0.104, ß=-0.289, P<0.001) and higher PDQ-39 (R²=0.052, ß=0.227, P<0.05) scores, while the association between CMBs and PDQ-39 disappeared after adjustment of MMSE or MoCA as a covariate. CONCLUSIONS The results suggest that hypertension was associated with the occurrence of deep CMBs. Comorbidity with CMBs may impair cognitive function and indirectly reduce the QoL in patients with PD.
