Stroke in Parkinson’s disease: a review of epidemiological studies and potential pathophysiological mechanisms

Elfil, Mohamed; Bayoumi, Ahmed; Sayed, Ahmed Kamal; Aladawi, Mohammad; Aboutaleb, Pakinam E.; Grieb, L.; Tolba, Hatem; Tinaz, Sule

doi:10.1007/s13760-023-02202-4

Cited by 7 publications

(4 citation statements)

References 102 publications

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“…There are several mechanisms by which PD could increase the risk of stroke ( 27 ). Motor dysfunction leading to reduced physical activity is the hallmark of PD.…”

Section: Discussionmentioning

confidence: 99%

Association between Parkinson's disease and the risk of adverse cardiovascular events: a systematic review and meta-analysis

Hu,

2023

Front. Cardiovasc. Med.

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BackgroundThis review aims to examine the association of Parkinson's disease (PD) with the increased risk of cardiovascular events.MethodsPubMed, Embase, CENTRAL, and Scopus databases were electronically searched for papers published up to 5 May 2023. Studies reporting the association between PD and the subsequent risks of stroke, myocardial infarction (MI), and cardiovascular mortality were included.ResultsSixteen studies were included in this review. The clinical data of 101,712 PD patients were compared with that of the control group of 204,901 patients without PD in the included studies. Meta-analysis showed that PD patients had an increased risk of stroke compared with patients without PD (odds ratio (OR): 1.49; 95% confidence interval (CI): 1.30, 1.72; I2 = 76%). The pooled analysis demonstrated no significant increase in the risk of MI (OR: 1.16; 95% CI: 0.85, 1.59; I2 = 82%) and cardiovascular mortality (OR: 1.20; 95% CI: 0.93, 1.54; I2 = 65%) in PD patients. However, data from cohort studies indicated a possibility of higher risk of MI (OR: 1.36; 95% CI: 1.01, 1.84; I2 = 80%) and cardiovascular mortality (OR: 1.22; 95% CI: 1.00, 1.60; I2 = 62%) in patients with PD.ConclusionPatients with PD may have an increased risk of stroke as compared with the age- and gender-matched general population. While our results show that PD does not increase the overall risk of MI and cardiovascular mortality, analysis of cohort studies alone demonstrated that these risks may be higher in patients with PD. The current evidence is of very low quality. Further prospective cohort studies from different countries that would account for important cardiovascular risk factors are needed to improve the current evidence.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/, PROSPERO (CRD42023421924).

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“…There are several mechanisms by which PD could increase the risk of stroke ( 27 ). Motor dysfunction leading to reduced physical activity is the hallmark of PD.…”

Section: Discussionmentioning

confidence: 99%

Association between Parkinson's disease and the risk of adverse cardiovascular events: a systematic review and meta-analysis

Hu,

2023

Front. Cardiovasc. Med.

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“…The MLi-2-treated RB group showed significant improvements in neurological deficit scores and behavioral test results. Considering the higher stroke risk in patients with PD with LRRK2 mutations [15] and the reports indicating that LRRK2 mutations induce an abnormal increase in its kinase activity contributing to PD pathology, our results suggest that LRRK2 inhibition in PD treatment could reduce So, how does pharmacological inhibition of LRRK2 work in stroke? The pattern of LRRK2/p-LRRK2-positive puncta suggests a link to physiological vesicle-mediated signaling pathways, such as autophagy.…”

Section: Discussionmentioning

confidence: 71%

“…Notably, recent studies have reported an elevated risk of stroke among PD patients [ 15 , 16 ]. Specifically, individuals with PD attributed to mutations in the LRRK2 gene appear to have a higher stroke risk than those with PD caused by other factors.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological Inhibition of LRRK2 Exhibits Neuroprotective Activity in Mouse Photothrombotic Stroke Model

Hwang,

Choi,

Kim

et al. 2024

Exp Neurobiol

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Leucine-rich repeat kinase 2 (LRRK2) mutations are the most common cause of Parkinson’s disease (PD). Interestingly, recent studies have reported an increased risk of stroke in patients with PD harboring LRRK2 mutations, but there is no evidence showing the functional involvement of LRRK2 in stroke. Here, we found that LRRK2 kinase activity was significantly induced in the Rose-Bengal (RB) photothrombosis-induced stroke mouse model. Interestingly, stroke infarct volumes were significantly reduced, and neurological deficits were diminished by pharmacological inhibition of LRRK2 kinase activity using MLi-2, a brain-penetrant LRRK2 kinase inhibitor. Immunohistochemical analysis showed p-LRRK2 level in stroke lesions, co-localizing with mitophagy-related proteins (PINK, Parkin, LC3B, cytochrome c), suggesting their involvement in stroke progression. Overlapping p-LRRK2 with cytochrome c/TUNEL/JC-1 (an indicator of mitochondrial membrane potential) puncta in RB photothrombosis indicated LRRK2-induced mitochondrial apoptosis, which was blocked by MLi-2. These results suggest that pharmacological inhibition of LRRK2 kinase activity could attenuate mitochondrial apoptosis, ultimately leading to neuroprotective potential in stroke progression. In conclusion, LRRK2 kinase activity might be neuro-pathogenic due to impaired mitophagy in stroke progression, and pharmacological inhibition of LRRK2 kinase activity could be beneficial in reducing the risk of stroke in patients with LRRK2 mutations.

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“…5). Such changes will cause further neurodegeneration hence establishing a vicious cycle, and this may be an undelaying mechanism for the observed association between neurodegeneration and atherosclerosis seen in AD [14,[17][18][19][20] and PD [75][76][77][78][79].…”

Section: Discussionmentioning

confidence: 99%

Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration

Thomsen,

Kostrikov,

Routhe

et al. 2024

Preprint

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Background: Chronic neurodegenerative diseases are characterized by substantial neuroinflammation with accumulation of macrophages, reactive microglia, and reactive astrocytes. Impairment of the brain vasculature is also commonly seen in chronic neurodegeneration with causal links warranting further investigation. Methods: To address the effects of chronic neurodegeneration on regional vasculature, we performed a unilateral injection of a glutamate receptor agonist ibotenic acid into striatum of adult rats, which caused excitotoxicity in the substantia nigra pars reticulata (SNpr) due to imbalance between inhibitory inputs from the striatum and excitatory signals from the subthalamic nucleus. Brains were examined at 28 days (short-term neurodegeneration) and 91 days (long-term neurodegeneration). Dissected brain samples were analyzed for protein and gene expression using immunohistochemistry and qPCR. Brains were further analyzed for remodeling of vasculature labeled with wheat germ agglutinin (WGA) Alexa Fluor 647 conjugate using 3D deep confocal microscopy of optically cleared samples combined with machine learning-based image analysis. Results: The resulting neurodegeneration was accompanied by neuroinflammation, verified by the expression of inflammatory markers with gradual, regional loss of brain tissue. An in-depth analysis of the angioarchitecture of the degenerating SNpr revealed substantial changes of the vasculature with higher density, increased diameter, and number of tortuous vessels already after 28 days continuing at 91 days. Interestingly, the vascular remodeling changes occurred without changes in the expression of endothelial tight junction proteins, vascular basement membrane proteins, or markers of angiogenesis. Conclusions: These results demonstrate how neurodegeneration causing prominent tissue loss in SNpr also leads to substantial remodeling of the angioarchitecture, while not altering the structural integrity of the vessel wall judged from the continuous expression of hallmarks of brain endothelial cells and the vascular basement membrane. We propose that this remodeling occurs as a consequence of the loss of brain tissue and with the resulting changes leaving the vasculature prone to additional vascular pathologies like vessel occlusion or formation of aneurysms.

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Stroke in Parkinson’s disease: a review of epidemiological studies and potential pathophysiological mechanisms

Cited by 7 publications

References 102 publications

Association between Parkinson's disease and the risk of adverse cardiovascular events: a systematic review and meta-analysis

Association between Parkinson's disease and the risk of adverse cardiovascular events: a systematic review and meta-analysis

Pharmacological Inhibition of LRRK2 Exhibits Neuroprotective Activity in Mouse Photothrombotic Stroke Model

Remodeling of the brain angioarchitecture in experimental chronic neurodegeneration

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