Heart rate variability in leucine-rich repeat kinase 2-associated Parkinson's disease.

BACKGROUND: Heart rate variability is reduced in idiopathic PD, indicating cardiac autonomic dysfunction likely resulting from peripheral autonomic synucleinopathy. Little is known about heart rate variability in leucine-rich repeat kinase 2-associated PD. OBJECTIVES: This study investigated heart rate variability in LRRK2-associated PD. METHODS: Resting electrocardiograms were obtained from 20 individuals with LRRK2-associated PD, 37 nonmanifesting carriers, 48 related noncarriers, 26 idiopathic PD patients, and 32 controls. Linear regression modelling compared time and frequency domain values, adjusting for age, sex, heart rate, and disease duration. RESULTS: Low-frequency power and the ratio of low-high frequency power were reduced in idiopathic PD versus controls (P < .008, P < .029 respectively). In contrast, individuals with LRRK2-associated PD were not statistically different from controls in any parameter measured. Furthermore, all parameters trended toward being higher in LRRK2-associated PD when compared with idiopathic PD. CONCLUSIONS: Heart rate variability may remain intact in LRRK2-associated PD, adding to a growing literature supporting clinical-pathologic differences between LRRK2-associated and idiopathic PD. © 2017 International Parkinson and Movement Disorder Society.

Dietary fat intake, pesticide use, and Parkinson's disease.

BACKGROUND: Dietary fat intake may modify Parkinson's disease (PD) risk directly or by altering the response to environmental neurotoxicants including pesticides. METHODS: We conducted a case-control study of PD nested in the Agricultural Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement disorder specialists, or a corresponding date in 336 frequency-matched controls. Associations were evaluated using multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: In the AHS, PD was inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI 0.2-0.8 for highest vs. lowest tertile) and the N-3 precursor α-linolenic acid (0.4, 0.2-0.8). In a meta-analysis of nine studies, including the present one, PD was inversely associated with α-linolenic acid (0.81, 0.68-0.96). In the AHS, associations of PD with the pesticides paraquat and rotenone were modified by fat intake. The OR for paraquat was 4.2 (1.5-12) in individuals with PUFA intake below the median but 1.2 (0.4-3.4) in those with higher intake (p-interaction = 0.10). The OR for rotenone was 5.8 (2.3-15) in those with saturated fat intake above the median but 1.5 (0.5-4.2) in those with lower intake (p-interaction = 0.02). CONCLUSIONS: PUFA intake was consistently associated with lower PD risk, and dietary fats modified the association of PD risk with pesticide exposure. If confirmed, these findings suggest that a diet high in PUFAs and low in saturated fats might reduce risk of PD.

Whole genome survey of coding SNPs reveals a reproducible pathway determinant of Parkinson disease.

It is quickly becoming apparent that situating human variation in a pathway context is crucial to understanding its phenotypic significance. Toward this end, we have developed a general method for finding pathways associated with traits that control for pathway size. We have applied this method to a new whole genome survey of coding SNP variation in 187 patients afflicted with Parkinson disease (PD) and 187 controls. We show that our dataset provides an independent replication of the axon guidance association recently reported by Lesnick et al. [PLoS Genet 2007;3:e98], and also indicates that variation in the ubiquitin-mediated proteolysis and T-cell receptor signaling pathways may predict PD susceptibility. Given this result, it is reasonable to hypothesize that pathway associations are more replicable than individual SNP associations in whole genome association studies. However, this hypothesis is complicated by a detailed comparison of our dataset to the second recent PD association study by Fung et al. [Lancet Neurol 2006;5:911-916]. Surprisingly, we find that the axon guidance pathway does not rank at the very top of the Fung dataset after controlling for pathway size. More generally, in comparing the studies, we find that SNP frequencies replicate well despite technologically different assays, but that both SNP and pathway associations are globally uncorrelated across studies. We thus have a situation in which an association between axon guidance pathway variation and PD has been found in 2 out of 3 studies. We conclude by relating this seeming inconsistency to the molecular heterogeneity of PD, and suggest future analyses that may resolve such discrepancies.