Higher Ischemic Stroke Risk Among Patients With Parkinson Disease With LRRK2 Variations

At MDS 2021, researchers shared study results on the effect of Parkinson disease (PD)-related genes on the risk for cardiovascular events among patients with genetic forms of PD, including those with variations in the LRRK2 and GBA genes.

The following article is part of conference coverage from the International Congress of Parkinson’s Disease and Movement Disorders (MDS) Virtual Annual Meeting. Neurology Advisor’s staff will be reporting breaking news associated with research conducted by leading experts in neurology. Check back for the latest news from the MDS 2021 Virtual Annual Meeting.


Among patients with Parkinson disease (PD), those with the leucine-rich repeat kinase 2 (LRRK2) gene (LRRK2-PD) may be at an increased risk for ischemic stroke, according to study findings presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS) Virtual Congress 2021, held from September 17 to 22, 2021.

Previous research has suggested PD is associated with a higher risk for ischemic stroke, but to date, no established relationship exists between PD and cardiovascular events. Researchers of the current study noted that the potential link between PD and ischemic stroke may go beyond the traditional risk factors.

The objective of the current study was to assess the effect of PD-related genes on vascular risk in patients with genetic forms of PD, including those with variations in the LRRK2 and glucocerebrosidase beta (GBA) genes, compared with patients with idiopathic PD and healthy control participants.

Patients with PD and healthy control participants were enrolled in the study from the Hospital Universitario Virgen del Rocío in Spain. Patients had etiologies of idiopathic PD (n=342), LRRK2-PD (n=31), and GBA-PD (n=30); a total of 641 control participants were also included in the study. Instances of radiologic-confirmed vascular events were compared between cohorts.

The common genetic variants were p.G2019S in 90.3% of the LRRK2-PD group and p.N370S in 40% of the GBA-PD group. All patient cohorts had similar disease durations (P =.13), Hoehen and Yahr scores (P =.57), and levodopa equivalent daily doses (P =.64). Onset of PD was significantly earlier among the GBA-PD (mean, 48.77±8.27 years) and LRRK2-PD cohorts (mean, 52.93±13.18) than among the idiopathic PD cohort (mean, 56.75±12.08; P <.05).

The control, idiopathic PD, GBA-PD, and LRKK2-PD groups included 54%, 60%, 73%, and 39% men (P <.05), respectively; patients in these groups were aged a mean of 60.82, 66.37, 48.77, and 64.84 years (P <.05), respectively.

After adjusting for age, sex, and vascular risk factors, the prevalence of ischemic stroke was 3.5% among control participants. However, patients with LRRK2-PD had a significantly higher prevalence of ischemic stroke (16.1%; P =.02), but not patients with idiopathic PD (4.7%) and those with GBA-PD (3.3%).

The age at ischemic stroke onset was 68.3±13.9 years in the control group and 62.2±15.7 years in the LRRK2-PD group. In addition, patients with LRRK2-PD had significantly lower cumulative survival (ci2=14.6; P =.006) compared with the other groups.

No significant differences among groups were observed for incidence of coronary artery disease (CAD; P =.554), age at CAD (P =.356), or cumulative CAD survival (P =.20).

The study may have been limited by the imbalance of patient characteristics at baseline.

These data indicated that patients with LRRK2-PD showed an increased risk for ischemic stroke at a younger age than other patient groups or control participants. With regard to stroke risk, patients with GBA-PD fared similarly to healthy control participants.

“Prospective and larger studies are needed to confirm these findings and to consider them in our routine clinical practice,” the researchers concluded.


Macías-García D, Periñán MT, Muñoz-Delgado L, et al. Increased stroke risk in Parkinson’s disease patients with LRRK2 mutations. Presented at: MDS Virtual Congress 2021; September 17-22, 2021. Poster 740.