D Ryglewicz

Institute of Psychiatry and Neurology, Warszawa, Masovian Voivodeship, Poland

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Publications (60)103.89 Total impact

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    ABSTRACT: Epigenetics (i.e. DNA methylation) together with the environmental and genetic factors are the key to understanding the pathogenesis of many diseases including dementia. Disturbances in DNA methylation have been already implicated in dementia. Homocysteine metabolism, with folate and vitamin B12 as essential cofactors, is integral to methylation processes. We evaluated the association of global DNA methylation, homocysteine, folate and B12 status with dementia. Selected polymorphisms of genes previously associated with dementia development and the influence of various factors on DNA methylation were also investigated. 102 patients with dementia (53 with Alzheimer’s disease, 17 with vascular dementia and 32 with mixed dementia) were recruited. The control group consisted of 45 age-matched subjects without dementia and 46 individuals with mild cognitive impairment. Global DNA methylation was determined by Imprint Methylated DNA Quantifcation Kit (Sigma-Aldrich). Serum homocysteine, folate, B12, creatinine, fasting glucose were determined by standard methods. Plasma and erythrocyte 5-methyltetrahydrofolate and plasma methylmalonic acid (markers of folate and B12 status) were measured by HPLC. APOE, PON1 p.Q192R, MTHFR c.677C > T and IL1B-511C > T polymorphisms were identified using PCR-RFLP. Subjects with dementia had significantly higher homocysteine (p = 0.012) and methylmalonic acid (p = 0.016) and lower folate (p = 0.002) and plasma 5-methyltetrahydrofolate (p = 0.005) than controls. There was no difference in DNA methylation between patients and controls. A tendency to higher DNA methylation in patients with vascular dementia (p = 0.061) was noted. Multivariate regression analysis of the whole group of investigated individuals demonstrated significant associations between DNA methylation and folate (p = 0.003), erythrocyte 5-methyltetrahydrofolate (p = 0.036), creatinine (p = 0.003) and glucose (p = 0.007) concentrations and IL1B-511C > T (p = 0.002) and PON1 p.Q192R (p = 0.044) genotypes. The association with MTHFR c.677C > T was significant only in controls (p = 0.017). The biochemical results showed significantly lower folate and B12 status in demented patients than controls. Global DNA methylation was associated with markers of folate status, creatinine, glucose and PON1 and IL1B polymorphisms.
    EuroLabFocus, CCLM; 10/2014
  • EuroLabFocus, eA220; 10/2014
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    ABSTRACT: AimsSelisistat, a selective SirT1 inhibitor is being developed as a potentially disease-modifying therapeutic for Huntington's disease (HD). This was the first study of selisistat in HD patients and was primarily aimed at development of pharmacodynamic biomarkers.Methods This was a randomized, double-blind, placebo-controlled, multicentre exploratory study. Fifty-five male and female patients in early stage HD were randomized to receive 10 mg or 100 mg of selisistat or placebo once daily for 14 days. Blood sampling, clinical and safety assessments were conducted throughout the study. Candidate pharmacodynamic markers included circulating soluble huntingtin and innate immune markers.ResultsSelisistat was found to be safe and well tolerated, and systemic exposure parameters showed that the average steady-state plasma concentration achieved at the 10 mg dose level (125 nm) was comparable with the IC50 for SirT1 inhibition. No adverse effects on motor, cognitive or functional readouts were recorded. While circulating levels of soluble huntingtin were not affected by selisistat in this study, the biological samples collected have allowed development of assay technology for use in future studies. No effects on innate immune markers were seen.Conclusions Selisistat was found to be safe and well tolerated in early stage HD patients at plasma concentrations within the anticipated therapeutic concentration range.
    British Journal of Clinical Pharmacology 09/2014; 79(3). DOI:10.1111/bcp.12512 · 3.88 Impact Factor
  • Joint Congress of European Neurology; 05/2014
  • A. Grotkowska · R. Rola · M. Restel · A. Bochynska · B. Sledz · D. Ryglewicz
    Joint Congress of European Neurology; 05/2014
  • Joint Congress of European Neurology; 05/2014
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    ABSTRACT: Due to the increasing incidence of Alzheimer's disease (AD), many studies have aimed to improve its diagnosis. Particular attention has been focused on measuring volumes of brain structures. Only few studies have investigated whether the cerebellar volume changes with the stage of dementia. It is controversial whether the serum apolipoprotein E (ApoE) level is an appropriate AD marker. This study was designed to clarify the significance of both cerebellar volume measurements and ApoE level measurements as markers of neurodegenerative changes. This study included 55 subjects with AD, 30 subjects with mild cognitive impairments (MCI), and a control group with 30 subjects. We measured the brain, cerebellum, and brain stem volumes with magnetic resonance imaging (MRI). We determined serum ApoE levels, APOE genotypes, and neuropsychological test scores. In the control group, we found that ApoE levels were significantly higher for subjects with the APOE 2/3 genotype than those with the 4/4 genotype. This finding may indicate that ApoE plays a protective role against AD development in subjects with the APOE 2/3 genotype. ApoE levels were not significantly different in patients with AD and MCI. No correlations were found between serum ApoE levels and Mini-Mental State Examination (MMSE) scores or the volumes of brain structures. This study could not confirm the appropriateness of the cerebellum volume as an early AD marker. Correlations were found between cerebellar volume, brain volume, and the MMSE scores.
    Current Alzheimer research 10/2013; 10(9). DOI:10.2174/15672050113106660161 · 3.89 Impact Factor
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    PLoS ONE 07/2013; · 3.23 Impact Factor
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    ABSTRACT: At 3 years after diagnosis, the risk of Alzheimer disease (AD) for patients with mild cognitive impairment (MCI) is estimated to be 18% to 30%. To improve treatment of patients at high dementia risk there is a need for a better prediction of the risk for transition from MCI to AD. Olfactory deficits are a hypothetical predictor of conversion form MCI to AD. Furthermore, several studies point at volumetric reduction of medial temporal lobe structures as predictors of conversion form MCI to AD. The primary aim of this study was to evaluate whether investigations of odor deficits in MCI combined with neuropsychological tests and MRI examinations can improve prediction of the development of dementia. Changes in olfactory functions, cognitive functions, and volume of medial temporal lobe structures (hippocampus, parahippocampal gyrus, and amygdala) were evaluated in a 24-month follow-up study in 49 MCI patients and 33 controls. In the MCI group, a prediction of strong cognitive functions deterioration based on poor performance in Olfactory Identification tests shows sensitivity of 57% and specificity of 88%. The test based on cognitive functions only shows a sensitivity of 44%, and 89%, respectively. Combined tests having a criteria of poor olfactory identification performance AND poor results of neuropsychological tests showed a sensitivity of 100% and specificity of 84%. Furthermore, correlation was found between the results of Olfactory Identification tests at baseline and deterioration of cognitive functions at follow up. Odor identification threshold did not appear to be a dementia predictor. A correlation of progress of cognitive function deterioration, odor identification deterioration, and decrease of volume of the hippocampus was also observed. Prediction of MCI to dementia conversion can be improved by supplementing the neuropsychological tests with odor identification tests. A follow up study of hippocampus volume reduction, OI performance and cognitive functions deterioration will further increase prediction accuracy.
    Current Alzheimer research 05/2011; 8(6):689-98. DOI:10.2174/156720511796717212 · 3.89 Impact Factor
  • Journal of the Neurological Sciences 08/2009; 283(1):306-306. DOI:10.1016/j.jns.2009.02.253 · 2.47 Impact Factor
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    ABSTRACT: In 229 patients with dementia and in 144 control subjects, polymorphisms of apolipoprotein E (ApoE), low-density-lipoprotein (LDL)-receptor-related protein, alpha(2)-macroglobulin, interleukin (IL) 1beta, angiotensin-converting enzyme and of methylene tetrahydrofolate reductase genes were investigated. In plasma, antibodies against Chlamydia pneumoniae and lipids were determined. Dementia was classified as probable Alzheimer's disease (AD), probable dementia of vascular origin (VaD) and mixed dementia (MD). An association of the disease with ApoE and IL-1beta polymorphism and increased levels of LDL cholesterol were observed in AD and in MD but not in VaD.
    Dementia and Geriatric Cognitive Disorders 02/2006; 22(1):1-7. DOI:10.1159/000092845 · 3.55 Impact Factor
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    ABSTRACT: Preclinical studies indicate that dopaminergic transmission in the basal ganglia may be involved in processing of both pleasant and unpleasant stimuli. Given this, the aim of the present study was to assess taste responses to sweet, bitter, sour, and salty substances in patients with Parkinson's disease (PD). Rated intensity and pleasantness of filter paper discs soaked in sucrose (10-60%), quinine (0.025-0.5%), citric acid (0.25-4.0%), or sodium chloride (1.25-20%) solutions was evaluated in 30 patients with PD and in 33 healthy controls. Paper discs soaked in deionised water served as control stimuli. In addition, reactivity to 100 ml samples of chocolate and vanilla milk was assessed in both groups. Taste detection thresholds were assessed by means of electrogustometry. Sociodemographic and neuropsychiatric data, including cigarette smoking, alcohol consumption, tea and coffee drinking, depressive symptoms, and cognitive functioning were collected. In general, perceived intensity, pleasantness, and identification of the sucrose, quinine, citric acid, or sodium chloride samples did not differ between the PD patients and controls. Intensity ratings of the filter papers soaked in 0.025% quinine were significantly higher in the PD patients compared with the control group. No inter-group differences were found in taste responses to chocolate and vanilla milk. Electrogustometric thresholds were significantly (p = 0.001) more sensitive in the PD patients. PD is not associated with any major alterations in responses to pleasant or unpleasant taste stimuli. Patients with PD may present enhanced taste acuity in terms of electrogustometric threshold.
    Journal of Neurology Neurosurgery & Psychiatry 02/2005; 76(1):40-6. DOI:10.1136/jnnp.2003.033373 · 6.81 Impact Factor
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    ABSTRACT: Poland has one of the highest rates of death due to stroke in Europe, which, in contrast to many industrialized countries, has not changed since at least 1984. To improve this unfavorable situation, the entire approach to stroke management needs to be recognized. For this purpose, an analysis of stroke epidemiology regarding regional differences was one of the the strategic points of the Polish National Project of Stroke Prevention and Treatment. The Polish National Stroke Registry was maintained from 1 January to 31 December 2000 in 59 Neurological Department in all 16 districts of Poland. In total 11,107 patients were included: 11% with intracerebral hemorrhage, 63.4% with ischemic stroke, and 25.6% with unclassified stroke. Computed tomography (CT) was performed in 73.6% of patients. Analysis of in-hospital deaths showed great differences between the centers (from 8% to 36%). According to multifactorial analysis, not only well-known predictors of early death (decrease in consciousness at the onset of stroke, decrease in functional state prior to stroke, and severity of stroke) influence the prognosis. In centers with high risk of death, CT, especially CT on admission, was performed significantly less often (4.2% vs. 62.6%), early rehabilitation was delayed (38.3% vs. 73.4%), and secondary prevention treatment was prescribed to fewer patients (antiplatelettherapy 36.4% vs. 77.4%; antithrombotic therapy 4.9% vs. 13%).
    Neurological Sciences 12/2003; 24(4):301-4. DOI:10.1007/s10072-003-0164-5 · 1.45 Impact Factor
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    ABSTRACT: Oxidative modification of human low density lipoprotein (LDL) plays an important role in the development of atherosclerosis. The aim of this study was to evaluate the oxidative modification of LDL in the group of patients with ischemic stroke. In the group of 43 patients 3 months after ischemic stroke and in the age and sex-matched control group, the kinetics of LDL oxidation and level of vitamin E were estimated. The susceptibility of LDL to oxidation was evaluated in isolated LDL exposed to in vitro oxidation. In 26 patients, after diet change, clinical and laboratory investigations were repeated 9 months later. In the patient group, susceptibility of LDL to oxidation was enhanced, lag phase was significantly shorter in comparison with the control group. After a change in diet, significant elongation of the lag phase was observed. Diet change improves LDL resistance to oxidation and may influence prognosis in stroke patients.
    Acta Neurologica Scandinavica 04/2002; 105(3):185-8. DOI:10.1034/j.1600-0404.2002.1o105.x · 2.40 Impact Factor
  • G Gromadzka · J Zielińska · Danuta Ryglewicz · Urszula Fiszer · A Członkowska
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    ABSTRACT: One of the important mechanisms involved in the development of vascular lesions leading to ischemic stroke could be an immune response to heat shock proteins (hsp). For carotid atherosclerosis and myocardial infarction, an association with an increase in anti-hsp 65 antibodies has been demonstrated. The aim of our study was (1) to investigate whether ischemic stroke is associated with a humoral immune response to hsp; (2) to study the connection between anti-hsp antibodies and other stroke risk factors; (3) to estimate if the elevated levels of anti-hsp antibodies could be an independent risk factor for stroke. We examined 180 patients (in the first 48 h after stroke onset) and 64 age-matched healthy controls. The levels of IgG and IgM antibodies to hsp 65 and 70 were measured by ELISA. Ischemic stroke was connected with a significant elevation of anti-hsp 65 and anti-hsp 70 antibody levels (IgG and IgM) compared with controls (p < 0.0001). The multifactorial logistic regression analysis showed that increased levels of anti-hsp 65 and anti-hsp 70 IgG antibodies are independent risk factors for stroke. Our results suggest that humoral immunity to hsp is common in stroke patients and that elevated levels of anti-hsp antibodies could be triggering factors for stroke.
    Cerebrovascular Diseases 10/2001; 12(3):235-9. DOI:10.1159/000047709 · 3.75 Impact Factor
  • T Mendel · J Popow · D Ryglewicz · A Członkowska
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    ABSTRACT: Clinico-pathological analysis of 207 patients dying after stroke was performed. The occurrence of atherosclerotic lesions in the aortic arch, thoracic and abdominal parts of aorta were compared in patients dying of ischaemic and haemorrhagic stroke. Advanced atherosclerotic lesions in the arch of aorta were rare in patients with ischaemic and haemorrhagic stroke. Moderate atherosclerotic lesions in the aortic arch were observed more frequently in ischaemic than in haemorrhagic stroke. Advanced atherosclerotic lesions in thoracic and abdominal part of aorta occurred with the same frequency in ischaemic and haemorrhagic stroke.
    Neurologia i neurochirurgia polska 01/2001; 35(1):23-34. · 0.64 Impact Factor
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    ABSTRACT: The aim of this work was the determination of apolipoprotein(a) [Lp(a)] in the patients three months after the onset of ischaemic stroke. A group of 56 patients was investigated. Stroke was diagnosed as caused by atherosclerotic changes in main cerebral arteries in 32 patients and in 11 by changes in cervical arteries. In 13 persons a lacunar stroke was recognised. The mean Lp(a) level and the median value were significantly higher in the group of patients after stroke as compared with 45 controls. A more frequent occurrence of Lp(a) level over 30 mg/dl considered as pathological was observed more often in the patients. No correlation was seen between Lp(a) and the resistance of LDL to oxidation nor between Lp(a) and the amount of products of LDL oxidation in vitro.
    Neurologia i neurochirurgia polska 01/2001; 35(1):35-40. · 0.64 Impact Factor
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    ABSTRACT: The aim of our work was to assess the usefulness of EEG in patients with seizures in acute phase of stroke. EEG patterns of 54 patients with epileptic seizures at the onset of stroke were evaluated: 45 of ischaemic, 6 of haemorrhagic origin and 3 with lacunar stroke as confirmed by CT or MR examination. Out of 40 patients, who had a single or multiple seizures at the onset of stroke, EEG revealed focal slow waves in 90% and in 22.5% they were accompanied by interictal epileptiform discharges. None of those patients had recurrent seizures during the time of hospitalisation irrespectively of applying antiepileptic drugs. In the remaining 14 patients prolonged disturbances of consciousness were observed. EEG examination revealed simple partial status epilepticus (SE) in 10 and complex partial SE in 4 of them. In 11 of those patients EEG disclosed fragments of periodic lateralized epileptiform discharges (PLED) interrupted by seizure activity. The findings indicate that in patients with seizures in the acute phase of stroke EEG examination is very helpful in making the proper therapeutic decision by recognizing the SE. The introduction of antiepileptic drugs is generally not necessary in stroke patients with single seizures.
    Neurologia i neurochirurgia polska 01/2001; 35(4):595-603. · 0.64 Impact Factor
  • T. Mendel · I. Baroni · W. Lechowicz · D. Ryglewicz · A. Członkowska
    Atherosclerosis 07/2000; 151(1):105-105. DOI:10.1016/S0021-9150(00)80475-X · 3.99 Impact Factor