Joseph Sagol Neuroscience Center

Ramat Gan, Israel

Joseph Sagol Neuroscience Center

Ramat Gan, Israel
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Katzav A.,Joseph Sagol Neuroscience Center | Shoenfeld Y.,Research Center for Autoimmune Diseases | Chapman J.,Joseph Sagol Neuroscience Center
Clinical Reviews in Allergy and Immunology | Year: 2010

Circulating antiphospholipid antibodies (aPL) are associated with central nervous system dysfunction in antiphospholipid syndrome (APS) patients and in a mouse model of APS. We propose a logical pathway of how experimental APS (eAPS) causes brain dysfunction: binding of the antibodies to the brain endothelium evoking micro-thrombosis, endothelial dysfunction, and IgG leakage through the blood-brain barrier (BBB), then secondary inflammatory cell spread around blood vessels and production of cytokines by these inflammatory cells leading to further disruption of the BBB. The diffuse brain endothelial dysfunction would result in extravasation of serum proteins including APS IgG and activated thrombin, which may induce the behavioral changes observed in the APS mice. We have collected data from the mouse eAPS model which supports this hypothesis. Elucidating the mechanism of the pathogenicity of aPL in vitro and in vivo will serve as a much needed basis for developing new therapeutic modalities in this important disorder. © Humana Press Inc. 2009.

Ravona-Springer R.,The Medical Memory | Heymann A.,Tel Aviv University | Schmeidler J.,Mount Sinai School of Medicine | Guerrero-Berroa E.,Mount Sinai School of Medicine | And 8 more authors.
Diabetes Care | Year: 2013

OBJECTIVE Haptoglobin (Hp) genotype (Hp 1-1, 1-2, or 2-2) is associated with risk for type 2 diabetes complications, but its relationship with cognitive compromise, a growing concern in type 2 diabetes, has rarely been studied. This study investigated whether Hp genotype is associated with cognitive function in cognitively normal elderly diabetic subjects. RESEARCH DESIGN AND METHODSdRelationships of Hp genotype with episodic memory, semantic categorization, attention/working memory and executive function, and an overall cognitive score were examined in subjects from the Israel Diabetes and Cognitive Decline (IDCD) study. RESULTSdIn the present analysis, 812 subjects participated (84 with Hp 1-1, 335 with Hp 1-2, and 393 with Hp 2-2 genotypes). Average was 72.9 years of age (SD 4.7), and Mini-Mental State Exam (MMSE) was 28.0 (SD 1.8). Compared with subjects with Hp 1-2 genotype, Hp 1-1 subjects performed significantly worse in semantic categorization (F = 7.03; P = 0.008) and the overall cognitive score (F = 5.57; P = 0.02). A separate stepwise multiple regression analysis demonstrated that compared with subjects with Hp 2-2 genotype, Hp 1-1 subjects performed significantlyworse in semantic categorization (F = 4.18; P = 0.04) and the overall cognitive score (F = 4.70; P = 0.03). The contribution of cardiovascular risk factors to cognition was significantly higher in subjects with Hp 1-1 genotype compared with Hp 2 carriers (Hp 1-2 and Hp 2-2) in the semantic categorization (P = 0.009) and attention/working memory (P = 0.002) cognitive domains. CONCLUSIONSdCompared with Hp 2 carriers, those with Hp 1-1 genotype present lower cognitive performance. Stronger relationships between cardiovascular risk factors and cognition in the latter group may suggest an underlying vascular mechanism. © 2013 by the American Diabetes Association.

Fogelson N.,Joseph Sagol Neuroscience Center | Litvak V.,University College London | Peled A.,Institute for Psychiatric Studies | Peled A.,Technion - Israel Institute of Technology | And 2 more authors.
Schizophrenia Research | Year: 2014

This paper tests the hypothesis that patients with schizophrenia have a deficit in selectively attending to predictable events. We used dynamic causal modeling (DCM) of electrophysiological responses - to predictable and unpredictable visual targets - to quantify the effective connectivity within and between cortical sources in the visual hierarchy in 25 schizophrenia patients and 25 age-matched controls. We found evidence for marked differences between normal subjects and schizophrenia patients in the strength of extrinsic backward connections from higher hierarchical levels to lower levels within the visual system. In addition, we show that not only do schizophrenia subjects have abnormal connectivity but also that they fail to adjust or optimize this connectivity when events can be predicted. Thus, the differential intrinsic recurrent connectivity observed during processing of predictable versus unpredictable targets was markedly attenuated in schizophrenia patients compared with controls, suggesting a failure to modulate the sensitivity of neurons responsible for passing sensory information of prediction errors up the visual cortical hierarchy. The findings support the proposed role of abnormal connectivity in the neuropathology and pathophysiology of schizophrenia. © 2014 The Authors.

Beeri M.S.,Mount Sinai School of Medicine | Beeri M.S.,Joseph Sagol Neuroscience Center | Sonnen J.,University of Utah
Neurology | Year: 2016

Despite great scientific efforts to find treatments for Alzheimer disease (AD), only 5 medications are marketed, with limited beneficial effects on symptoms, on a limited proportion of patients, without modification of the disease course. The prevalence of AD doubles every 5 years, reaching the alarming rate of 50% in those aged 85 years and older. In the context of the demographic trends of modern society, where the elderly are the fastest growing segment of the population, identification of new therapeutic targets that may prevent, delay, or cure AD is critically needed. © 2016 American Academy of Neurology.

Ravona-Springer R.,The Medical Memory | Ravona-Springer R.,Joseph Sagol Neuroscience Center | Schnaider-Beeri M.,Joseph Sagol Neuroscience Center | Schnaider-Beeri M.,Mount Sinai School of Medicine | And 2 more authors.
Neurology | Year: 2013

Objective: To analyze the relationship between body weight variability and dementia more than 3 decades later. Methods: The measurement of body weight variability was based on 3 successive weight recordings taken from over 10,000 apparently healthy tenured working men participating in the Israel Ischemic Heart Disease study, in which cardiovascular risk factors and clinical status were assessed in 1963, 1965, and 1968, when subjects were 40-70 years of age. Groups of men were stratified according to quartiles of SD of weight change among 3 measurements (1963/1965/1968): ≤1.15 kg, 1.16-1.73 kg, 1.74-2.65 kg, and $2.66 kg. The prevalence of dementia was assessed more than 36 years later in approximately one-sixth of them who survived until 1999/2000 (minimum age 76 years) and underwent cognitive evaluation (n = 1,620). Results: Survivors' dementia prevalence rates were 13.4%, 18.4%, 20.1%, and 19.2% in the first to fourth quartiles ofweight change SD, respectively (p for trend5 0.034). Compared to the first quartile of weight change SD and adjusted for diabetes mellitus, body height, and socioeconomic status, a multivariate analysis demonstrated that the odds ratio for dementia was 1.42 (95% confidence interval [CI] 0.95-2.13), 1.59 (95% CI 1.05-2.37), and 1.74 (95% CI 1.14-2.64) in quartiles 2-4 of weight change SD respectively. This relationship was independent of the direction of weight changes. Conclusion: Midlife variations in weight may antecede late-life dementia. © 2013 American Academy of Neurology.

Kravitz E.,Joseph Sagol Neuroscience Center | Schmeidler J.,Mount Sinai School of Medicine | Schnaider Beeri M.,Joseph Sagol Neuroscience Center | Schnaider Beeri M.,Mount Sinai School of Medicine
Endocrinology and Metabolism Clinics of North America | Year: 2013

Type 2 diabetes, like dementia, disproportionately affects the elderly. Diabetes has consistently been associated with risk of dementia, mild cognitive impairment, and cognitive decline suggesting that cognitive compromise is a deleterious manifestation of diabetes. This review summarizes observational studies and clinical trials of diabetes medications and their respective associations and effects on cognitive outcomes. Despite biological plausibility, results from most human clinical trials have failed to show any efficacy in treating Alzheimer disease symptomatology and pathology. Clinical trials targeting vascular-related outcomes, diabetic patients, or cognitively normal elderly at risk for dementia, may provide greater cognitive benefits. © 2013 Elsevier Inc.

Oriel S.,Ben - Gurion University of the Negev | Dori A.,Joseph Sagol Neuroscience Center | Kofman O.,Ben - Gurion University of the Negev
Behavioural Pharmacology | Year: 2014

The long-term effects of postnatal exposure to an organophosphate substance diisopropylfluorophosphate (DFP) were examined on fear conditioning in adult mice. Immediate and long-term changes in the expression of synaptic acetylcholinesterase (AChE-S) and readthrough acetylcholinesterase (AChE-R) transcripts were explored, in view of reports relating expression of these splice variants to stress and anxiety. BALB/c and C57BL/6 mice were injected daily, on postnatal days 4-10, with 1mg/kg of DFP or saline and tested as adults for cued and contextual freezing and scanning. Real-time PCR was used to investigate expression of the rare AChE-R and AChE-S mRNA postnatally and in fear-conditioned adults. DFP-pretreated male mice showed increased conditioned cued scanning and both male and female DFP-treated mice showed enhanced contextual scanning. DFP abolished the stress-induced increase in AChE transcript expression in BALB/c but not in C57BL/6 mice. A significant correlation was found between expression of AChE-S and AChE-R transcripts in the hippocampus and scanning behavior, but this was apparently unrelated to DFP treatment. The enhanced conditioned scanning in adults, following postnatal exposure to DFP, suggests long-term effects on the risk for anxiety disorders. The altered expression of AChE splice variant transcripts in the two strains did not account for the behavioral deficits, which were observed in both BALB/c and C57BL/6 strains. © 2014 Wolters Kluwer Health.

Inzelberg R.,Joseph Sagol Neuroscience Center | Inzelberg R.,Tel Aviv University | Weinberger M.,Tel Aviv University | Gak E.,Joseph Sagol Neuroscience Center | Gak E.,Tel Aviv University
Parkinsonism and Related Disorders | Year: 2011

Benign hereditary chorea (BHC, MIM 118700) is a rare autosomal dominant disorder manifesting with chorea in conjunction with hypothyroidism and respiratory problems, a triad also named " brain-lung-thyroid syndrome" BHC is characterized by childhood onset with minimal or no progression into adult life and normal cognitive function.The genetic basis of BHC has been partially resolved, when mutations in the TTF1 gene on chromosome 14q13 encoding the thyroid transcription factor-1 have been identified in a number of BHC patients, suggesting that aberration of TTF1 transcriptional function or haploinsufficiency is associated with this disorder. TTF1 (also known as TITF1, TEBP or NKX2-1), belonging to the NKX2 homeodomain transcription factor family, has been implicated in several important molecular pathways essential for brain, thyroid and lung morphogenesis. Clinical evaluation of TTF1 gene mutations carrier patients exposed the involvement of each of the triad's components characterized by heterogeneity between index cases and even within families. This review highlights the current updates on expanded clinical aspects of BHC, imaging and treatment experience, its genetic markers, proposed molecular mechanisms, animal models and link to cancer. © 2011 Elsevier Ltd.

Faust-Socher A.,Joseph Sagol Neuroscience Center | Faust-Socher A.,Tel Aviv University | Kenett Y.N.,Bar - Ilan University | Cohen O.S.,Joseph Sagol Neuroscience Center | And 5 more authors.
Annals of Neurology | Year: 2014

Objective Creative thinking requires a combination of originality, flexibility, and usefulness. Several reports described enhanced artistic creativity in Parkinson disease (PD) patients treated with dopaminergic agents. We aimed to examine PD patients' ability to perform creativity tasks compared to healthy controls and to verify whether creativity is related to an impulse control disorder (ICD) as a complication of dopaminergic therapy. Methods Right-handed PD patients treated with dopamine agonists and/or levodopa, and age- and education- matched neurologically healthy controls were assessed using the Montreal Cognitive Assessment, semantic verbal fluency, Beck Depression Inventory, and Questionnaire for Impulsive-Compulsive Disorders in Parkinson Disease Rating Scale (QUIP-RS). Creativity assessment included Comprehension of Novel Metaphors (CNM), Remote Association Test, and Tel Aviv Creativity Test (TACT). Groups were compared using analyses of variance, t tests, and correlation analyses. Results Twenty-seven PD patients (age, mean ± standard deviation = 62 ± 7 years; education = 16 ± 3 years; disease duration = 5.8 ± 3.9 years) and 27 controls (age = 59 ± 9 years; education 17 ± 3 years) participated. PD patients performed significantly better than controls in divergent thinking tasks; specifically, the TACT-Visual for both fluency (33.48 ± 11.83 vs 25.59 ± 10.27, p = 0.034) and quality (15.78 ± 7.6 vs 11.19 ± 6.22, p = 0.025). Comprehension of Novel Metaphors was better in PD patients vs controls (0.71 ± 0.23 vs 0.55 ± 0.29, p = 0.04). QUIP-RS scores did not correlate with creativity measures. Interpretation PD patients treated with dopaminergic drugs demonstrated enhanced verbal and visual creativity as compared to neurologically healthy controls. This feature was unrelated to ICD. Dopaminergic agents might act through the reduction of latent inhibition, resulting in widening of the associative network and enriched divergent thinking. Ann Neurol 2014;75:935-942 © 2014 American Neurological Association.

Ravona-Springer R.,The Medical Memory | Beeri M.S.,Mount Sinai School of Medicine | Beeri M.S.,Joseph Sagol Neuroscience Center | Goldbourt U.,Tel Aviv University
Journal of Alzheimer's Disease | Year: 2013

The present study aimed to assess the relationship of midlife Motivation to Improve Status at work (MIS) with dementia more than three decades later. In 1963, 9,920 out of 10,059 male participants of the Israel Ischemic Heart disease (IIHD) study, aged 40-65 years, were questioned about their MIS as follows: 'Do you want to improve your status at work and do you believe it is possible?'. One of four answers was possible: trying to change status and believe it is possible (MIS1) (n = 3,060); trying but unsure of success (MIS2) (n = 2,618); not trying, unlikely to succeed (MIS3) (n = 2,020); not trying, satisfied (MIS4) (n = 2,222). Dementia was assessed over three decades later in 1,714 survivors of the original cohort, including 1,691 who responded in 1963 to the questionnaire regarding MIS. Controlling for age, the estimated odds for dementia relative to MIS1 were 1.45 (95% CI 1.06-2.01) in MIS2, 1.52 (95% CI 1.04-2.23) in MIS3, and 1.96 (95% CI 1.38-2.81) in MIS4. Further adjustment for age and socioeconomic status index resulted in adjusted estimated odds for dementia relative to MIS1 were 1.26 (95% CI 0.90-1.75) in MIS2, 1.10 (95% CI 0.74-1.64) in MIS3, and 1.78 (95% CI 1.23-2.56) in MIS4. These results were not attenuated when midlife diabetes, blood pressure values, serum-cholesterol levels, and coronary heart disease were controlled for in the analysis. Among tenured working men, lack of MIS together with satisfaction with current status was associated with higher risk for dementia among survivors several decades later. This association was partially attenuated by socioeconomic status. © 2013 - IOS Press and the authors. All rights reserved.

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