Avner Thaler

Avner Thaler
Tel Aviv Sourasky Medical Center | TASMC · Department of Neurology

MD, PhD

About

67
Publications
7,461
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1,182
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Introduction
Avner Thaler currently works at the Neurological institute, Tel Aviv Medical Center affiliated with Tel-Aviv University. Research interests include genetics of Parkinson's disease, Multiple System Atrophy, Imaging and prodromal Parkinson's disease
Additional affiliations
August 2011 - present
Tel Aviv Sourasky Medical Center
Position
  • Medical Doctor
August 2008 - February 2016
Tel Aviv University
Position
  • Medical Doctor

Publications

Publications (67)
Article
Background: As Parkinson's disease (PD) progresses, response to oral medications decreases and motor complications appear. Timely intervention has been demonstrated as effective in reducing symptoms. However, current instruments for the identification of these patients are often complicated and inadequate. It has been suggested that anti-PD intens...
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Introduction: Patients with advanced Parkinson's disease (PD) may require device-aided therapies (DAT) for adequate symptom control. However, long-term, real-world efficacy and safety data are limited. This study aims to describe real-world, long-term treatment persistence for patients with PD treated with levodopa-carbidopa intestinal gel (LCIG)....
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Non-manifesting carriers (NMCs) of Parkinson’s disease (PD)-related mutations such as LRRK2 and GBA are at an increased risk for developing PD. Dopamine transporter (DaT)-spectral positron emission computed tomography is widely used for capturing functional nigrostriatal dopaminergic activity. However, it does not reflect other ongoing neuronal pro...
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Introduction There have been no specific guidelines regarding which genes should be tested in the clinical setting for PD or parkinsonism. We evaluated the types of clinical genetic testing offered for Parkinson’s disease (PD) as the first step of our gene curation. Methods The National Institutes of Health (NIH) Genetic Testing Registry (GTR) was...
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Background: Mutations in the GBA gene, which encodes the lysosomal enzyme glucocerebrosidase (GCase), are risk factors for Parkinson's disease (PD). Objective: To explore the association between GCase activity, PD phenotype, and probability for prodromal PD among carriers of mutations in the GBA and LRRK2 genes. Methods: Participants were geno...
Article
ObjectiveT1-weighted MRI images are commonly used for volumetric assessment of brain structures. Magnetization prepared 2 rapid gradient echo (MP2RAGE) sequence offers superior gray (GM) and white matter (WM) contrast. This study aimed to quantitatively assess the agreement of whole brain tissue and deep GM (DGM) volumes obtained from MP2RAGE compa...
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Pathogenic C9orf72-G4C2 repeat expansions are associated with ALS/FTD, but not with Parkinson’s disease (PD); yet the possible link between intermediate repeat lengths and PD remains inconclusive. We aim to study the potential involvement of these repeats in PD. The number of C9orf72-repeats were determined by flanking and repeat-primed PCR assays,...
Article
Introduction The prevalence of subtle cognitive decline in the early stages of Parkinson's Disease (PD) is common and is thought to be even greater in patients carrying genetic mutations in the GBA gene. Current cognitive tests often lack sensitivity to identify subtle impairments. Technological advancements may offer greater precision. We explored...
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Introduction the: GBA-N370S mutation is one of the most frequent risk factors for dementia with Lewy bodies (DLB) and Parkinson's disease (PD). We looked for genetic variations that contribute to the outcome in N370S-carriers, whether PD or DLB. Methods: Whole-genome sequencing of 95 Ashkenazi-N370S-carriers affected with either DLB (n = 19) or...
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Background: Inflammation is an integral part of neurodegeneration including in Parkinson's disease (PD). Ashkenazi Jews have high rates of genetic PD with divergent phenotypes among GBA-PD and LRRK2-PD. The role of inflammation in the prodromal phase of PD and the association with disease phenotype has yet to be elucidated. Objective: To assess...
Article
Background: It is not clear how specific gait measures reflect disease severity across the disease spectrum in Parkinson's disease (PD). Objective: To identify the gait and mobility measures that are most sensitive and reflective of PD motor stages and determine the optimal sensor location in each disease stage. Methods: Cross-sectional wearab...
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Background The phenotype of Parkinson’s disease (PD) is variable with mutations in genes such as LRRK2 and GBA explaining part of this heterogeneity. Additional genetic and environmental factors contribute to disease variability. Objective To assess the association between biochemical markers, PD severity and probability score for prodromal PD, am...
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Importance: Despite a hypothesis that harboring a leucine-rich repeat kinase 2(LRRK2) G2019S variation and a glucocerebrosidase (GBA) variant would have a combined deleterious association with disease pathogenesis, milder clinical phenotypes have been reported in dual LRRK2 and GBA variations Parkinson disease (PD) than in GBA variation PD alone....
Article
GBA variations are common risk factors for Parkinson's disease (PD), and are found in 21.7% of Ashkenazi PD patients (AJ-PD), 4.23% of them carry an allele, 370Rec, which is different from the common GBA-N370S allele. Using whole-genome-sequencing of 370Rec carriers, N370S carriers, and non-carriers, we characterize the unique 370Rec haplotype in A...
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Background: Glucocerebrosidase (GBA) gene mutations and APOE polymorphisms are common in dementia with Lewy bodies (DLB), however their clinical impact is only partially elucidated. Objective: To explore the clinical impact of mutations in the GBA gene and APOE polymorphisms separately and in combination, in a cohort of Ashkenazi Jewish (AJ) pat...
Article
Background: Cerebrospinal fluid (CSF) is essential for the medical workup of patients with neurological conditions as for disease-modifying clinical trials. Post- lumbar puncture (LP) headache is influenced by both operator and patient factors, including needle type and gauge, age and gender. Objectives: We aimed to assess whether CSF volume as mea...
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In order toevaluate the influence of the metabolic syndrome (MS) (obesity, hypertension, elevated triglycerides, reduced levels of HDL cholesterol and glucose impairment) on the phenotype of LRRK2 and GBA Parkinson’s disease (PD), and on the prevalence of prodromal features among individuals at risk, we collected, laboratory test results, blood pre...
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Background The phenotype of Parkinson's disease (PD) is milder among patients with LRRK2‐PD and more severe among patients with GBA‐PD; however, whether an additive phenotypical effect occurs among dual‐mutation carriers requires validation. Objective The objective of this study was to explore the phenotypic expression of patients with PD who carr...
Article
Background: Sleep disturbances and nocturnal hypokinesia are common in Parkinson's disease (PD). Recent work using wearable technologies showed fewer nocturnal movements in PD when compared with controls. However, it is unclear how these manifest across the disease spectrum. Objectives: We assessed the prevalence of sleep disturbances and noctur...
Article
Background: The effect of repeated intravenous amantadine (IVAM) in advanced Parkinsonism has not been studied in depth. Objectives: To report the experience of our medical center with repeated IVAM infusions in patients with advanced Parkinsonism. Methods: Thirty patients with advanced Parkinsonism of various etiologies were enrolled in an op...
Article
Background: GBA variants are the most common genetic risk factors for Parkinson's disease (PD) world-wide, and can be found in up to 20% of Ashkenazi PD patients. The E326K variant, which is not considered a Gaucher's disease causing mutation, was recently shown to increase the risk for PD. Since E326K is a common variant among Europeans, Finnish...
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Disturbances in reward processing occur in Parkinson's disease (PD) however it is unclear whether these are solely drug-related. We applied an event-related fMRI gambling task to a group of non-manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene, in order to assess the reward network in an "at risk" population for future development...
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Mutations in the LRRK2 and GBA genes are the most common inherited causes of Parkinson's disease (PD). Studies exploring phenotypic differences based on genetic status used hypothesis-driven data-gathering and statistical-analyses focusing on specific symptoms, which may influence the validity of the results. We aimed to explore phenotypic expressi...
Article
Non‐manifesting carriers (NMC) of the G2019S mutation in the LRRK2 gene represent an “at risk” group for future development of Parkinson's disease (PD) and have demonstrated task related fMRI changes. However, resting‐state networks have received less research focus, thus this study aimed to assess the integrity of the motor, default mode (DMN), sa...
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Cognitive deficits beyond memory impairment, such as those affecting language production or executive functioning, can be useful in clinically distinguishing between dementia syndromes. We tested the hypothesis that Ashkenazi Jewish (AJ) patients who have dementia with Lewy bodies (DLB) and carry glucocerebrosidase (GBA) mutations will have verbal...
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Cerebral atrophy has been detected in patients with Parkinson’s disease (PD) both with and without dementia, however differentiation based on genetic status has thus far not yielded robust findings. We assessed cortical thickness and subcortical volumes in a cohort of PD patients and healthy controls carriers of the G2019S mutation in the LRRK2 gen...
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Background: The G2019S mutation in the LRRK2 gene generates a milder PD phenotype compared with GBA‐PD; however, genetic based survival studies are lacking. Objectives: To compare mortality rates between LRRK2‐PD, GBA‐PD, and idiopathic PD patients (iPD). Methods: Patients were screened for the G2019S mutation in the LRRK2 gene and the seven common...
Article
Introduction: Patients with Gilles de la Tourette syndrome (GTS) experience reduced function and impaired quality of life. The current medical treatments for this syndrome can cause significant side effects and offer partial symptomatic relief. In a few small trials medical cannabis (MC) has been suggested to offer symptomatic relief with a relati...
Article
Objective: Mutations in the glucocerebrosidase (GBA) gene are divided into mild and severe (mGBA, sGBA) based on their contribution to the phenotype of Gaucher disease (GD) among homozygotes. We conducted a longitudinal analysis of Parkinson's disease (PD) patients carrying mutations in the GBA gene to better characterize genotype-phenotype correl...
Article
Background In 2015, the International Parkinson and Movement Disorder Society Task Force recommended research criteria for the estimation of prodromal PD. Objectives We aimed to evaluate, for the first time, the criteria in first‐degree relatives of Ashkenazi Jewish G2019S‐LRRK2 PD patients, who are considered a population at risk for developing P...
Article
Importance Few prospective longitudinal studies have evaluated the progression of Parkinson disease (PD) in patients with the leucine-rich repeat kinase 2 (LRRK2 [OMIM 609007]) mutation. Knowledge about such progression will aid clinical trials. Objective To determine whether the longitudinal course of PD in patients with the LRRK2 mutation differ...
Chapter
Between 10 and 15% of Parkinson disease (PD) cases can be traced to a genetically identified causative mutation which currently number over 40. This enables the study of both “at risk” populations for future development of PD and a unique sub-group of genetically determined patient population. Structural and functional magnetic imaging has the pote...
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Major methodological advancements have been recently made in the field of neural decoding, which is concerned with the reconstruction of mental content from neuroimaging measures. However, in the absence of a large-scale examination of the validity of the decoding models across subjects and content, the extent to which these models can be generaliz...
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Background: The Movement Disorders Society (MDS) published the English new Unified Parkinson's Disease Rating Scale (MDS-UPDRS) as the official benchmark scale for Parkinson's disease (PD) in 2008. We aimed to validate the Hebrew version of the MDS-UPDRS, explore its dimensionality and compare it to the original English one. Methods: The MDS-UPD...
Article
Background: Worldwide prevalence estimates of Huntington disease (HD) vary widely, with no reliable information regarding the Jewish population in Israel. Methods: This specialized tertiary single-center cross-sectional study assessed clinical, cognitive, and demographic characteristics of 84 HD patients who were treated at the Movement Disorder...
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Identification of early changes in Dopamine-Transporter (DaT) SPECT imaging expected in the prodromal phase of Parkinson's disease (PD), are usually overlooked. Carriers of the G2019S LRRK2 mutation are known to be at high risk for developing PD, compared to non-carriers. In this work we aimed to study early changes in Dopamine uptake in non-manife...
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Mutations in the GBA and LRRK2 genes account for one-third of the prevalence of Parkinson’s disease (PD) in Ashkenazi Jews. Non-manifesting carriers (NMC) of these mutations represent a population at risk for future development of PD. PD patient who carry mutations in the GBA gene demonstrates more significant cognitive decline compared to idiopath...
Article
Objective: Mutations in the GBA gene are associated with Parkinson's disease (PD). A definite description of the clinical characteristics of PD patients who are compound heterozygotes or homozygotes for mutations in the GBA gene (GD-PD) requires further elucidation. Methods: We assessed motor, cognitive, olfactory and autonomic functions as well...
Article
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...
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While the phenotype of Parkinson disease (PD) is heterogeneous, treatment approaches are mostly uniform. Personalized medicine aims to treat diseases with targeted therapies based on cumulative variables including genotype. We believe that sufficient evidence has accumulated to warrant the initiation of personalized medicine in PD based on subjects...
Article
Cognitive impairments are prevalent in patients with Parkinson's disease. Mutations in the leucine rich repeat kinase 2 (LRRK2) gene are the most common cause of genetic Parkinsonism. Non-manifesting carriers of the G2019S mutation in the LRRK2 gene were found to have lower executive functions as measured by the Stroop task. This exploratory study...
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Healthy walking is characterized by pronounced arm swing and axial rotation. Aging effects on gait speed, stride length and stride time variability have been previously reported, however, less is known about aging effects on arm swing and axial rotation and their relationship to age-associated gait changes during usual walking and during more chall...
Article
Background The asymptomatic carriers of the Leucine rich repeat kinase 2 (LRRK2) G2019S mutation represent a population at risk for developing PD. The aim of this study was to assess differences in nonmotor symptoms between nonmanifesting carriers and noncarriers of the G2019S mutation.Methods Two hundred fifty-three subjects participated in this o...
Article
We investigated system-level corticostriatal changes in a human model of premotor Parkinson disease (PD), i.e., healthy carriers of the G2019S LRRK2 mutation that is associated with a markedly increased, age-dependent risk of developing PD. We compared 37 asymptomatic LRRK2 G2019S mutation carriers (age range 30-78 years) with 32 matched, asymptoma...
Article
Background Patients with Parkinson's disease have reduced gray matter volume and fractional anisotropy in both cortical and sub-cortical structures, yet changes in the pre-motor phase of the disease are unknown. MethodsA comprehensive imaging study using voxel-based morphometry and diffusion tensor imaging tract-based spatial statistics analysis wa...
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The phenotype of Parkinson's disease (PD) in patients with and without leucine-rich repeat kinase 2 (LRRK2) G2019S mutations reportedly is similar; however, large, uniformly evaluated series are lacking. The objective of this study was to characterize the clinical phenotype of Ashkenazi Jewish (AJ) PD carriers of the LRRK2 G2019S mutation. We studi...
Article
Patients with Parkinson's disease (PD) who carry the G2019S mutation (a glycine to serine substitution at amino acid 2019) in the leucine-rich repeat kinase 2 (LRRK2) gene are generally believed to be clinically indistinguishable from patients with sporadic PD. There are, however, conflicting reports on the relationship between the mutation and the...
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Background. Adipose tissue is an important endocrine organ that secretes cytokines, including adiponectin, levels of which are negatively correlated with the severity of the inflammatory process. Aim. To assess the time course of adiponectin levels following open heart surgery with cardiopulmonary bypass and its correlation with early postoperative...
Article
Compensatory cerebral mechanisms can delay motor symptom onset in Parkinson's disease. We aim to characterize these compensatory mechanisms and early disease-related changes by quantifying movement-related cerebral function in subjects at significantly increased risk of developing Parkinson's disease, namely carriers of a leucine-rich repeat kinase...
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Objective: To assess cognitive abilities of healthy first-degree relatives of Ashkenazi patients with Parkinson disease (PD), carriers of the G2019S mutation in the LRRK2 gene. Methods: In this observational study, 60 consecutive healthy first-degree relatives (aged 50.9 ± 6.2 years; 48% male; 30 G2019S carriers) were assessed using a computeriz...
Article
Neural selectivity to specific object categories has been demonstrated in extrastriate cortex with both functional MRI [1-3] and event-related potential (ERP) [4, 5]. Here we tested for a causal relationship between the activation of category-selective areas and ERP to their preferred categories. Electroencephalogram (EEG) was recorded while partic...
Article
Parkinson's disease (PD) has a long pre-diagnosis phase that may span as long as 10-20 years. The ability to identify at risk populations raises the possibility of early intervention to delay or prevent the onset of motor symptoms. In Israel, there is a large group of Ashkenazi Jews at risk of developing PD due to high frequency of PD associated mu...
Article
Fractalkine (FKN), a unique chemokine associated with pulmonary hypertension, may be involved in the acute stress response that regulates inflammation after cardiopulmonary bypass (CPB) surgery. We characterized FKN levels and correlated them with clinical parameters in children undergoing cardiac surgery involving CPB. Twenty-seven consecutive pat...
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Mutations in the leucine rich repeat kinase 2 gene (LRRK2) are recognized as the most common cause of genetic Parkinsonism to date. The G2019S mutation has been implicated as an important determinant of Parkinson's disease (PD) in both Ashkenazi Jewish and North African Arab populations with carrier frequency of 29.7% among familial and 6% in spora...

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