Objective: Our study aimed to characterise Parkinson disease (PD) mild cognitive impairment (PD-MCI) in early PD and to identify biomarkers associated with PD-MCI.

Background: Approximately 20% of PD patients have PD-MCI and PD-MCI increases the risk of having dementia in PD. Several biomarkers are associated with PD-MCI based on literature, including amyloid-β, a-synuclein, tau protein, APOE-ε4 and EGF. Some studies have found the link of hypertriglyceride with cognitive impairment, but few in PD and in PD-MCI. We therefore aim to characterise and study these risk factors in our cohort of PD-MCI.

Methods: Demographic and clinical information were prospectively collected from 160 early PD patients. Detailed neuropsychological testing (≥2 tests/domain) was conducted and PD-MCI was characterised by the MDS level II criteria. Participants also underwent blood analysis and genotyping for serum uric acid, serum lipid profile, APOE-ε4 and LRRK2 variants.

Results: PD-MCI was prevalent in this early PD cohort, with 73.8% of the cohort having PD-MCI at 1.0 SD cut-offs, 52.5% at 1.5 SDs cut-offs, and 33.8% at 2.0 SDs cut-offs. PD-MCI was predominantly multi-domain subtype (>90%) at all cut-off levels. Memory domain was consistently the most frequently affected domain, followed by language and visuospatial domain. Patients with PD-MCI had significantly higher serum triglyceride levels (105.70 ± 47.86 mg/dL vs. 80.57 ± 35.67 mg/dL, p=0.0004) compared to cognitively normal PD patients. Higher serum triglyceride level remained significantly associated with PD-MCI (p=0.0035, OR=5.056) after adjusting for confounders, including CVS risk, BMI, total serum cholesterol, and APOE-ε4 status. In individual five cognitive domains, serum triglyceride levels were significantly inversely correlated with standardised scores of memory domain (β: -0.4044, p=0.0440), visuospatial domain (β: -0.4110, p=0.0283), language domain (β: -0.3411, p=0.0419), and executive domain (β: -0.5147, p=0.0003), independent from potential confounders. None of the genotypes tested had significantly association with PD-MCI.

Conclusions: PD-MCI is prevalent in early PD and is associated with higher serum triglyceride levels. Triglyceride levels are a potential modifiable risk factor for PD-MCI.

References: Kalia, L. V. (2018). Biomarkers for cognitive dysfunction in Parkinson’s disease. Parkinsonism & Related Disorders, 46, S19–S23. https://doi.org/10.1016/j.parkreldis.2017.07.023. Farr, S. A., Yamada, K. A., Butterfield, D. A., Abdul, H. M., Xu, L., Miller, N. E., Banks, W. A. & Morley, J. E. (2008). Obesity and Hypertriglyceridemia Produce Cognitive Impairment. Endocrinology, 149(5), 2628–2636. https://doi.org/10.1210/en.2007-1722.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/hypertriglyceridemia-is-associated-with-parkinson-disease-mild-cognitive-impairment-pd-mci/