Discussion
stroke, Alzheimer’s disease, PD, CAD, Lewy body diseases, Lewy
CVD, STROKE, LEWY BODY DISEASE, DISEASES, PATHOGENESIS, CAD
Our study reveals a potential relationship between PD and CAD and stroke (including subtypes IS, CES), which is consistent with the results of previous small cohort studies, but past cohort studies were smaller and had a lower level of evidencePD is the second most common neurodegenerative condition after Alzheimer’s disease in terms of prevalenceWe explored the relationship between PD and CAD by five MR methods, and all findings consistently suggested an association between PD and increased incidence of CAD. For the effect of PD on the increased incidence of CAD, we believe that the following mechanisms exist: First, PD is a Lewy body diseases, and excessive deposition of Lewy bodies in PD patients was clarified and reported in 1997, and excessive deposition of Lewy bodies leads to cardiac sympathetic denervationThe relationship between PD and stroke has been studied more in the past, some studies have suggested that PD causes an increased risk of stroke, mainly related to abnormalities in α-synuclein metabolism, α-synuclein is a 14.5 kDa protein located predominantly in the presynaptic terminals of the mammalian brain, and over-accumulates in Lewy bodies upon gene expressionThis MR study also have some limitations, first, due to racial differences in GWAS data, its test results may be affected by population stratification bias. Second, since most of the population in this study originated in Europe, we are not sure if the same conclusions can be drawn in other populations. Third, the potential pleiotropy of some SNPs may affect the detection results. Fourth, there were some sample duplications in the included studies, which could have led to biased MR estimates, but the F-statistic we detected were all greater than 10, and the assessment of this bias should be small.In conclusion, we explored the relationship between PD and cvd at the genetic level for the first time using MR analysis, an approach that excludes environmental confounders and reverse causality bias that have been seen in previous observational studies, and provides additional clues to the pathogenesis of PD and cardio-cerebrovascular diseases as well as to therapeutic regimens. The results suggest that PD may be a potential pathogenetic factor for CAD and stroke, which is consistent with previous animal and clinical observations studies. This suggests that it is more important to achieve early screening and treatment of CAD and stroke in patients with PD.