Cognitive and behavioral symptoms in Parkinson's disease patients with the G2019S and R1441G mutations of the LRRK2 gene

Somme, Johanne; Salazar, Ana Molano; González, Anaisa Hernández; Tijero, Beatriz; Berganzo, Koldo; Lezcano, Elena; Fernández-Martı́nez, Manuel; Zarranz, J.J.; Gómez‐Esteban, Juan Carlos

doi:10.1016/j.parkreldis.2015.02.019

Cited by 45 publications

(36 citation statements)

References 30 publications

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“… a Marras et al , 2011; b Alcalay et al , 2013; c Somme et al , 2015; d Ehrminger et al , 2015; e Kertelge et al , 2010; f Alcalay et al , 2014; g Sixel-Doring et al , 2015; h Simon-Tov et al , 2015; i Alcalay et al , 2012; j Neumann et al , 2009; k Gan-Or et al , 2015; l Konno et al , 2016; m Petrucci et al , 2016; n Nishioka et al , 2009.…”

Section: Neurobiology Underlying Visual Changes: Genetic Basis For Hementioning

confidence: 99%

Visual dysfunction in Parkinson’s disease

Weil

Schrag

Warren

et al. 2016

Brain

357

285

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Section: Neurobiology Underlying Visual Changes: Genetic Basis For Hementioning

confidence: 99%

Visual dysfunction in Parkinson’s disease

Weil

Schrag

Warren

et al. 2016

Brain

357

285

View full text Add to dashboard Cite

show abstract

“…A multicentre study suggested lower risk of early cognitive decline in 162 LRRK2 patients, compared to 340 non-carriers [10]. Several smaller studies have reported trends in the same direction [11][12][13]. A large Chinese study found no effect of two Asian LRRK2 variants on cognitive outcomes, but these were polymorphisms carrying only a small effect on PD risk [14].…”

Section: Lrrk2 à Leucine-rich Repeat Kinasementioning

confidence: 99%

Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature

Fagan

Pihlstrøm

2017

Euro J of Neurology

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Parkinson's disease is a highly heterogeneous disorder, where genetic factors are likely to contribute to clinical variability, including susceptibility to cognitive impairment and dementia. Monogenic forms of parkinsonism show distinct cognitive profiles, yet less is known about the impact of common genetic variants on cognition in sporadic Parkinson's disease. In a systematic review of the literature, the current results from genetic association studies of cognitive outcomes are summarized and prospects and challenges for future studies are discussed. Literature searches of the PubMed database were performed and studies using statistical methods to assess associations between genetic variation and any cognitive outcome in Parkinson's disease patients were included. For each of the candidate loci investigated in several studies, the current evidence is summarized and discussed. Sixty-one articles meeting our inclusion criteria were identified, which were highly heterogeneous with respect to study design, size and cognitive outcome measures. GBA mutations have a negative impact on cognition, whereas LRRK2-associated disease may have a milder cognitive phenotype than idiopathic Parkinson's disease. For common variants, reported results are partly conflicting, even across the larger studies, with some evidence to suggest a potential effect of APOE, MAPT, COMT and SNCA on cognitive outcomes. Future investigations should aim to collect high-quality cognitive data in a standardized way that allows for direct comparison across studies and large-scale meta-analysis. Linking genetic profiles to cognitive outcomes may have an important clinical impact, facilitating the stratification of patients for clinical trials and, ultimately, individualized treatment in Parkinson's disease.

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“…On the contrary, LRRK2 PD is reported to be associated with less risk of cognitive dysfunction, RBD, hyposmia, and slower rate of motor progression . There are some reports of higher prevalence of psychiatric symptoms associated with LRRK2 PD, although the data are not consistent . Although there is a growing body of literature examining motor, nonmotor, and imaging characteristics of LRRK2 and GBA PD carriers, there are still limited data from large, controlled, prospective longitudinal cohort studies comparing early‐stage GBA and LRRK2 PD to sporadic PD (sPD) specifically focusing on nonmotor manifestations as well as allowing comparisons between GBA and LRRK2 PD cohorts .…”

mentioning

confidence: 99%

Clinical and Dopamine Transporter Imaging Characteristics of Leucine Rich Repeat Kinase 2 (LRRK2) and Glucosylceramidase Beta (GBA) Parkinson's Disease Participants in the Parkinson's Progression Markers Initiative: A Cross‐Sectional Study

et al. 2020

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Background There are limited data on the phenotypic and dopamine transporter (DAT) imaging characterization of the Parkinson's disease (PD) patients with leucine rich kinase 2 (LRRK2) and glucosylceramidase beta (GBA) mutations. Objective The objective of this study was to examine baseline clinical and DAT imaging characteristics in GBA and LRRK2 mutation carriers with early PD compared with sporadic PD. Methods The Parkinson's Progression Markers Initiative is an ongoing observational longitudinal study that enrolled participants with sporadic PD, LRRK2 and GBA PD carriers from 33 sites worldwide. All participants are assessed annually with a battery of motor and nonmotor scales, 123‐I Ioflupane DAT imaging, and biologic variables. Results We assessed 158 LRRK2 (89% G2019S), 80 GBA (89 %N370S), and 361 sporadic PD participants with the mean (standard deviation) disease duration of 2.9 (1.9), 3.1 (2.0), and 2.6 (0.6) years, respectively. When compared with sporadic PD, the GBA PD patients had no difference in any motor, cognitive, or autonomic features. The LRRK2 PD patients had less motor disability and lower rapid eye movement behavior disorder questionnaire scores, but no meaningful difference in cognitive or autonomic features. Both genetic cohorts had a higher score on the impulse control disorders scale when compared with sporadic PD, but no difference in other psychiatric features. Both genetic PD cohorts had less loss of dopamine transporter on DAT imaging when compared with sporadic PD. Conclusions We confirm previous reports of milder phenotype associated with LRRK2‐PD. A previously reported more aggressive phenotype in GBA‐PD is not evident early in the disease in N370s carriers. This observation identifies a window for potential disease‐modifying interventions. Longitudinal data will be essential to define the slope of progression for both genetic cohorts. Trial Registration http://clinicaltrials.gov (NCT01141023). © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Cognitive and behavioral symptoms in Parkinson's disease patients with the G2019S and R1441G mutations of the LRRK2 gene

Cited by 45 publications

References 30 publications

Visual dysfunction in Parkinson’s disease

Visual dysfunction in Parkinson’s disease

Genetic risk factors for cognitive decline in Parkinson's disease: a review of the literature

Clinical and Dopamine Transporter Imaging Characteristics of Leucine Rich Repeat Kinase 2 (LRRK2) and Glucosylceramidase Beta (GBA) Parkinson's Disease Participants in the Parkinson's Progression Markers Initiative: A Cross‐Sectional Study

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