1.
Parkinson Disease and Subthalamic Nucleus Deep Brain Stimulation: Cognitive Effects in GBA Mutation Carriers
Pal, Gian; Mangone, Graziella; Hill, Emily J. ...
Annals of neurology,
March 2022, Letnik:
91, Številka:
3
Journal Article
Objective
This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain ...
stimulation (STN‐DBS) in Parkinson disease.
Methods
Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS‐), and noncarriers with or without DBS (GBA‐DBS+, GBA‐DBS‐). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status.
Results
Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS‐, 98 GBA‐DBS+, and 128 GBA‐DBS‐ subjects), who were longitudinally followed (range = 36–60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA‐DBS‐ subjects (95% confidence interval CI = −2.35 to −1.69), 1.71 points/yr more than GBA+DBS‐ subjects (95% CI = −2.14 to −1.28), and 1.49 points/yr more than GBA‐DBS+ subjects (95% CI = −1.80 to −1.18).
Interpretation
Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN‐DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision‐making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN‐DBS so that alternative options may be considered. ANN NEUROL 2022;91:424–435
več
2.
Penetrance estimate of LRRK2 p.G2019S mutation in individuals of non‐Ashkenazi Jewish ancestry
Lee, Annie J.; Wang, Yuanjia; Alcalay, Roy N. ...
Movement disorders,
October 2017, Letnik:
32, Številka:
10
Journal Article
ABSTRACT
Background
Penetrance estimates of the leucine‐rich repeat kinase 2 (LRRK2) p.G2019S mutation for PD vary widely (24%‐100%). The p.G2019S penetrance in individuals of Ashkenazi Jewish ...
ancestry has been estimated as 25%, adjusted for multiple covariates. It is unknown whether penetrance varies among different ethnic groups. The objective of this study was to estimate the penetrance of p.G2019S in individuals of non‐Ashkenazi Jewish ancestry and compare penetrance between Ashkenazi Jews and non‐Ashkenazi Jews to age 80.
Methods
The kin‐cohort method was used to estimate penetrance in 474 first‐degree relatives of 69 non‐Ashkenazi Jewish LRRK2 p.G2019S carrier probands at 8 sites from the Michael J. Fox LRRK2 Cohort Consortium. An identical validated family history interview was administered to assess age at onset of PD, current age, or age at death for relatives in different ethnic groups at each site. Neurological examination and LRRK2 genotype of relatives were included when available.
Results
Risk of PD in non‐Ashkenazi Jewish relatives who carry a LRRK2 p.G2019S mutation was 42.5% (95% confidence interval CI: 26.3%‐65.8%) to age 80, which is not significantly higher than the previously estimated 25% (95% CI: 16.7%‐34.2%) in Ashkenazi Jewish carrier relatives. The penetrance of PD to age 80 in LRRK2 p.G2019S mutation carrier relatives was significantly higher than the noncarrier relatives, as seen in Ashkenazi Jewish relatives.
Conclusions
The similar penetrance of LRRK2 p.G2019S estimated in Ashkenazi Jewish carriers and non‐Ashkenazi Jewish carriers confirms that p.G2019S penetrance is 25% to 42.5% at age 80 in all populations analyzed. © 2017 International Parkinson and Movement Disorder Society
več
3.
Arm swing as a potential new prodromal marker of Parkinson's disease
Mirelman, Anat; Bernad-Elazari, Hagar; Thaler, Avner ...
Movement disorders,
10/2016, Letnik:
31, Številka:
10
Journal Article
ABSTRACT
Background
Reduced arm swing is a well‐known clinical feature of Parkinson's disease (PD), often observed early in the course of the disease. We hypothesized that subtle changes in arm swing ...
and axial rotation may also be detectable in the prodromal phase.
Objective
The purpose of this study was to evaluate the relationship between the LRRK2‐G2019S mutation, arm swing, and axial rotation in healthy nonmanifesting carriers and noncarriers of the G2019S mutation and in patients with PD.
Methods
A total of 380 participants (186 healthy nonmanifesting controls and 194 PD patients) from 6 clinical sites underwent gait analysis while wearing synchronized 3‐axis body‐fixed sensors on the lower back and bilateral wrists. Participants walked for 1 minute under the following 2 conditions: (1) usual walking and (2) dual‐task walking. Arm swing amplitudes, asymmetry, variability, and smoothness were calculated for both arms along with measures of axial rotation.
Results
A total of 122 nonmanifesting participants and 67 PD patients were carriers of the G2019S mutation. Nonmanifesting mutation carriers walked with greater arm swing asymmetry and variability and lower axial rotation smoothness under the dual task condition when compared with noncarriers (P < .04). In the nonmanifesting mutation carriers, arm swing asymmetry was associated with gait variability under dual task (P = .003). PD carriers showed greater asymmetry and variability of movement than PD noncarriers, even after controlling for disease severity (P < .009).
Conclusions
The G2019S mutation is associated with increased asymmetry and variability among nonmanifesting participants and patients with PD. Prospective studies should determine if arm swing asymmetry and axial rotation smoothness may be used as motor markers of prodromal PD. © 2016 International Parkinson and Movement Disorder Society
več
4.
Differences in Sex‐Specific Frequency of Glucocerebrosidase Variant Carriers and Familial Parkinsonism
Ortega, Roberto A.; Bressman, Susan B.; Raymond, Deborah ...
Movement disorders,
November 2022, Letnik:
37, Številka:
11
Journal Article
Background
Although men and women with the LRRK2 G2019S variant appear to be equally likely to have Parkinson's disease (PD), the sex‐distribution among glucocerebrosidase (GBA) variant carriers with ...
PD, including limited to specific variant severities of GBA, is not well understood. Further, the sex‐specific genetic contribution to PD without a known genetic variant is controversial.
Objectives
To better understand sex differences in genetic contribution to PD, especially sex‐specific frequencies among GBA variant carriers with PD (GBA PD) and LRRK2‐G2019S variant carriers with PD (LRRK2 PD).
Methods
We assess differences in the sex‐specific frequency in GBA PD, including in subsets of GBA variant severity, LRRK2 PD, and idiopathic PD in an Ashkenazi Jewish cohort with PD. Further, we expand prior work evaluating differences in family history of parkinsonism.
Results
Both idiopathic PD (267/420 men, 63.6%) (P < 0.001) and GBA PD overall (64/107, 59.8%) (P = 0.042) were more likely to be men, whereas no difference was seen in LRRK2 PD (50/99, 50.5%) and LRRK2/GBA PD (5/10, 50%). However, among GBA PD probands, severe variant carriers were more likely to be women (15/19 women, 79.0%) (P = 0.005), whereas mild variant carriers (44/70 men, 62.9%) (P = 0.039) and risk‐variant carriers (15/17 men, 88.2%) (P = 0.001) were more likely to be men.
Conclusions
Our study demonstrates that the male‐sex predominance present in GBA PD overall was not consistent across GBA variant severities, and a female‐sex predominance was present among severe GBA variant carriers. Therefore, research and trial designs for PD should consider sex‐specific differences, including across GBA variant severities. © 2022 International Parkinson and Movement Disorder Society.
več
5.
6.
Genetic Testing in Parkinson's Disease
Pal, Gian; Cook, Lola; Schulze, Jeanine ...
Movement disorders,
August 2023, Letnik:
38, Številka:
8
Journal Article
Genetic testing for persons with Parkinson's disease is becoming increasingly common. Significant gains have been made regarding genetic testing methods, and testing is becoming more readily ...
available in clinical, research, and direct‐to‐consumer settings. Although the potential utility of clinical testing is expanding, there are currently no proven gene‐targeted therapies, but clinical trials are underway. Furthermore, genetic testing practices vary widely, as do knowledge and attitudes of relevant stakeholders. The specter of testing mandates financial, ethical, and physician engagement, and there is a need for guidelines to help navigate the myriad of challenges. However, to develop guidelines, gaps and controversies need to be clearly identified and analyzed. To this end, we first reviewed recent literature and subsequently identified gaps and controversies, some of which were partially addressed in the literature, but many of which are not well delineated or researched. Key gaps and controversies include: (1) Is genetic testing appropriate in symptomatic and asymptomatic individuals without medical actionability? (2) How, if at all, should testing vary based on ethnicity? (3) What are the long‐term outcomes of consumer‐ and research‐based genetic testing in presymptomatic PD? (4) What resources are needed for clinical genetic testing, and how is this impacted by models of care and cost‐benefit considerations? Addressing these issues will help facilitate the development of consensus and guidelines regarding the approach and access to genetic testing and counseling. This is also needed to guide a multidisciplinary approach that accounts for cultural, geographic, and socioeconomic factors in developing testing guidelines. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
več
7.
8.
Inflammatory Bowel Disease and Parkinson's Disease: A Nationwide Swedish Cohort Study
Weimers, Petra; Halfvarson, Jonas; Sachs, Michael C ...
Inflammatory bowel diseases,
01/2019, Letnik:
25, Številka:
1
Journal Article
Few studies have examined the association between inflammatory bowel disease (IBD) and Parkinson's disease (PD).
To estimate the incidence and relative risk of PD development in a cohort of adult ...
IBD, we included all incident IBD patients (n = 39,652) in the Swedish National Patient Register (NPR) between 2002 and 2014 (ulcerative colitis UC: n = 24,422; Crohn's disease CD: n = 11,418; IBD-unclassified IBD-U: n = 3812). Each IBD patient was matched for sex, age, year, and place of residence with up to 10 reference individuals (n = 396,520). In a cohort design, all incident PD occurring after the index date was included from the NPR. In a case-control design, all incident PD occurring before the index date was included. The association between IBD and PD and vice versa was investigated by multivariable Cox and logistic regression.
In IBD, there were 103 cases of incident PD, resulting in hazard ratios (HRs) for PD of 1.3 (95% confidence interval CI, 1.0-1.7; P = 0.04) in UC, 1.1 (95% CI, 0.7-1.7) in CD, and 1.7 (95% CI, 0.8-3.0) in IBD-U. However, these effects disappeared when adjusting for number of medical visits during follow-up to minimize potential surveillance bias. In a case-control analysis, IBD patients were more likely to have prevalent PD at the time of IBD diagnosis than matched controls, with odds ratios of 1.4 (95% CI, 1.2-1.8) in all IBD patients, 1.4 (95% CI, 1.1-1.9) for UC, and 1.6 (95% CI, 1.1-2.3) for CD patients alone.
IBD is associated with an increased risk of PD, but some of this association might be explained by surveillance bias. 10.1093/ibd/izy190_video1izy190.video15785623138001.
več
Naroči gradivo
9.
Cervical dystonia incidence and diagnostic delay in a multiethnic population
LaHue, Sara C.; Albers, Kathleen; Goldman, Samuel ...
Movement disorders,
March 2020, Letnik:
35, Številka:
3
Journal Article
Background
Current cervical dystonia (CD) incidence estimates are based on small numbers in relatively ethnically homogenous populations. The frequency and consequences of delayed CD diagnosis is ...
poorly characterized.
Objectives
To determine CD incidence and characterize CD diagnostic delay within a large, multiethnic integrated health maintenance organization.
Methods
We identified incident CD cases using electronic medical records and multistage screening of more than 3 million Kaiser Permanente Northern California members from January 1, 2003, to December 31, 2007. A final diagnosis was made by movement disorders specialist consensus. Diagnostic delay was measured by questionnaire and health utilization data. Incidence rates were estimated assuming a Poisson distribution of cases and directly standardized to the 2000 U.S. census. Multivariate logistic regression models were employed to assess diagnoses and behaviors preceding CD compared with matched controls, adjusting for age, sex, and membership duration.
Results
CD incidence was 1.18/100,000 person‐years (95% confidence interval CI, 0.35–2.0; women, 1.81; men, 0.52) based on 200 cases over 15.4 million person‐years. Incidence increased with age. Half of the CD patients interviewed reported diagnostic delay. Diagnoses more common in CD patients before the index date included essential tremor (odds ratio OR 68.1; 95% CI, 28.2–164.5), cervical disc disease (OR 3.83; 95% CI, 2.8–5.2), neck sprain/strain (OR 2.77; 95% CI, 1.99–3.62), anxiety (OR 2.24; 95% CI, 1.63–3.11) and depression (OR 1.94; 95% CI, 1.4–2.68).
Conclusions
CD incidence is greater in women and increases with age. Diagnostic delay is common and associated with adverse effects. © 2019 International Parkinson and Movement Disorder Society
več
10.
International Genetic Testing and Counseling Practices for Parkinson's Disease
Saunders‐Pullman, Rachel; Raymond, Deborah; Ortega, Roberto A. ...
Movement disorders,
August 2023, Letnik:
38, Številka:
8
Journal Article
Background
There is growing clinical and research utilization of genetic testing in Parkinson's disease (PD), including direct‐to‐consumer testing.
Objectives
The aim is to determine the ...
international landscape of genetic testing in PD to inform future worldwide recommendations.
Methods
A web‐based survey assessing current practices, concerns, and barriers to genetic testing and counseling was administered to the International Parkinson and Movement Disorders Society membership.
Results
Common hurdles across sites included cost and access to genetic testing, and counseling, as well as education on genetic counseling. Region‐dependent differences in access to and availability of testing and counseling were most notable in Africa. High‐income countries also demonstrated heterogeneity, with European nations more likely to have genetic testing covered through insurance than Pan‐American and Asian countries.
Conclusions
This survey highlights not only diversity of barriers in different regions but also the shared and highly actionable needs for improved education and access to genetic counseling and testing for PD worldwide. © 2023 International Parkinson and Movement Disorder Society.
več
PDF