H Wehr

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

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Publications (50)94.73 Total impact

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    ABSTRACT: We assess PON1 activity and anti-ox LDL antibodies in large group of elderly individuals in Poland.•PON1 activity significantly decreased with advancing age and was lower in males than in females.•PON1 activity decreased in persons with impaired cognition.•PON1 activity was inversely related to levels of inflammation indicators.•Anti-ox LDL antibodies level was significantly higher in the oldest subgroups of males.
    Archives of Gerontology and Geriatrics 11/2014; DOI:10.1016/j.archger.2014.10.010 · 1.53 Impact Factor
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    ABSTRACT: The aim of the article is to review the current knowledge of mechanisms linking adipokines, insulin resistance and dementia. Adipose tissue secretes into the bloodstream a number of hormones named adipokines, which regulate many aspects of the metabolism and energy balance. They also play a role in blood pressure regulation, hemostasis and immunity, and in the development of various pathological conditions which are often accompanied by insulin resistance. Leptin and adiponectin are important adipokines related with dementia. Both diminish insulin resistance, can cross the blood/brain barrier and exert influence on nervous tissue. It has been found that leptin accelerates beta amyloid disintegration and also decreases tau phosphorylation, thus favoring the removal of two of the main pathological elements of Alzheimer disease and creating future therapeutic possibilities. Adiponectin decreases glucose levels by increasing the oxidation of fatty acids and inhibiting gluconeogenesis. Adiponectin is produced as monomer, which can change into a more active multimeric form. Some of the polymorphic forms of adiponectin favor its multimerization. Other adipokines – resistin and adipokine – like ghrelin are also connected with dementia. The possibility of using resistin in Alzheimer disease therapy has been raised. Ghrelin's role in neuroprotection, memory consolidation and cognitive functions has been found showing a relationship between ghrelin and Alzheimer disease. Adipokines play an important role in the mechanisms connected with dementia.
    Postepy Psychiatrii i Neurologii 10/2014; DOI:10.1016/j.pin.2014.09.004
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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; DOI:10.2174/15672050113106660161 · 4.97 Impact Factor
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    ABSTRACT: Paraoxonase 1 (PON1) activity was determined using phenylacetate as substrate (arylesterase activity) in 304 individuals with dementia - 136 recognised as probable Alzheimer's disease (AD), 64 as dementia of vascular origin (VaD) and 104 as mixed dementia (MD) and in 129 persons without symptoms of dementia and in a good general health. -108C>T polymorphism in the PON1 gene promoter and p.Q192R polymorphism in the coding region were identified. PON1 activity was significantly lower in demented patients as compared with controls particularly in dementia of a neurodegenerative character (AD and MD). The prevalence of PON1-108T allele carriers was significantly higher in the AD group than in controls. The frequencies of the p.Q192R genotypes did not differ significantly between the investigated groups. An association of the rare T-R haplotype with dementia, particularly with dementia of the neurodegenerative type, was found. Multivariate regression analysis showed a significant association of PON1 activity with PON1 -108C>T and p.Q192R polymorphisms. The influence not only of promoter -108C>T, but also of p.Q192R polymorphism on PON1 arylesterase activity was observed. One has to admit that this kind of polymorphism does not preclude interference with the enzyme activity. It could be concluded that the PON1 gene promoter polymorphism plays an additional role in Alzheimer's disease development. It seems however that PON1 activity has a dominating influence on the dementia risk.
    01/2013; 51(2):111-119. DOI:10.5114/fn.2013.35953
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    ABSTRACT: Paraoxonase 1 (PON1) activity and metabolic syndrome traits were evaluated in 169 demented patients (81 recognized as AD, 32 as VaD, 56 as MD) and in 64 control individuals. Paraoxonase activity was determined spectrophotometrically using phenyloacetate as substrate. Metabolic syndrome was recognized according to AHA/NHLBI criteria. In the whole group with dementia significant positive correlation between PON1 activity/HDL cholesterol ratio (i.e. HDL corrected PON1 activity) and insulin level as well as HOMA IR index, was observed. The multivariate analysis showed that the PON1/HDL-C ratio was also significantly positively associated with the presence of metabolic syndrome (with insulin resistance as a major underlying trait) both in dementia and in control group. High insulin level and HOMA-IR are considered to be the traits of insulin resistance. It has however to be taken into account that they both could also depend on insulin production and release which, as was recently stated in cell experiments, are enhanced by PON1. The observed positive correlation suggests an advantageous role of the enzyme in metabolic syndrome influence on dementia development.
    Journal of the neurological sciences 11/2012; DOI:10.1016/j.jns.2012.11.003 · 2.32 Impact Factor
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    ABSTRACT: Autosomal dominant hypercholesterolemia (ADH) is caused by mutations in the genes coding for the low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB), or proprotein convertase subtilisin/kexin type 9 (PCSK9). In this study, a molecular analysis of LDLR and APOB was performed in a group of 378 unrelated ADH patients, to explore the mutation spectrum that causes hypercholesterolemia in Poland. All patients were clinically diagnosed with ADH according to a uniform protocol and internationally accepted WHO criteria. Mutational analysis included all exons, exon-intron boundaries and the promoter sequence of the LDLR, and a fragment of exon 26 of APOB. Additionally, the MLPA technique was applied to detect rearrangements within LDLR. In total, 100 sequence variations were identified in 234 (62%) patients. Within LDLR, 40 novel and 59 previously described sequence variations were detected. Of the 99 LDLR sequence variations, 71 may be pathogenic mutations. The most frequent LDLR alteration was a point mutation p.G592E detected in 38 (10%) patients, followed by duplication of exons 4-8 found in 16 individuals (4.2%). Twenty-five cases (6.6%) demonstrated the p.R3527Q mutation of APOB. Our findings imply that major rearrangements of the LDLR gene as well as 2 point mutations (p.G592E in LDLR and p.R3527Q in APOB) are frequent causes of ADH in Poland. However, the heterogeneity of LDLR mutations detected in the studied group confirms the requirement for complex molecular studies of Polish ADH patients.
    Journal of applied genetics 03/2010; 51(1):95-106. DOI:10.1007/BF03195716 · 1.90 Impact Factor
  • Journal of the Neurological Sciences 08/2009; 283(1):306-306. DOI:10.1016/j.jns.2009.02.253 · 2.26 Impact Factor
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    ABSTRACT: Vascular cognitive impairment is an important cause of cognitive decline in the elderly. Ischemic lesions in the brain have an influence on the natural history of dementia. Vascular dementia can be caused by small-vessels disease (S-VaD) or by large-artery atherosclerosis with vascular lesions in strategic areas of the brain (M-VaD). In both cases changes in white matter are observed. In 60 patients with S-VaD and in 34 with M-VaD the presence of vascular and biochemical risk factors was evaluated and compared to age and sex matched 126 controls without dementia. Coronary artery disease, atrial fibrillation, hypertension and strokes were observed more frequently in both investigated groups. Of biochemical risk factors, hyperhomocysteinemia (associated with low levels of folic acid and vitamin B 12) and low HDL cholesterol levels were found in both forms of VaD.
    Journal of the neurological sciences 04/2009; 283(1-2):116-8. DOI:10.1016/j.jns.2009.02.344 · 2.32 Impact Factor
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    ABSTRACT: In serum of 114 patients with dementia and of 102 controls the level of IG class immunoglobulins directed against oxidized LDL and lipids were determined. In isolated DNA apolipoprotein E gene (APOE) polymorphism was identified. In some individuals very high levels of the antibodies were observed. exceeding the 90 percentile in the investigated group. The prevalence of very high anti-ox LDL antibodies level was significantly more frequent in the carriers of epsilon2 allele and less frequent in the carriers of epsilon4 allele.
    Journal of the neurological sciences 04/2009; 283(1-2):137-8. DOI:10.1016/j.jns.2009.02.345 · 2.32 Impact Factor
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    ABSTRACT: Paraoxonase activity, homocysteine level and lipids were determined in 120 patients with dementia (51 with Alzheimer disease, 28 with dementia of vascular origin, 41 with mixed dementia), 45 with mild cognitive impairment and in 61 age and sex matched controls without dementia. Paraoxonase activity was decreased in Alzheimer disease and in mixed dementia as compared with control group. In the same forms of dementia homocysteine levels were increased. In Alzheimer disease paraoxonase activity was negatively correlated with homocysteine levels. Minimental State Examination results showed positive correlation with paraoxonase activity. The results suggest an important role of oxidative stress in the development of the forms of dementia with prevailing neurodegeneration.
    Journal of the neurological sciences 04/2009; 283(1-2):107-8. DOI:10.1016/j.jns.2009.02.317 · 2.32 Impact Factor
  • Atherosclerosis Supplements 06/2006; 7(3):135-135. DOI:10.1016/S1567-5688(06)80535-0 · 9.67 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 · 2.81 Impact Factor
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    ABSTRACT: To investigate the influence of apolipoprotein E (APOE) and angiotensin-converting enzyme (ACE) gene polymorphisms on carotid artery atherosclerosis in alcoholism. Polymorphism of both genes was identified by DNA analysis in 130 male alcohol-dependent patients. Intima-media thickness (IMT) was measured ultrasonographically. Multivariate regression analysis showed that of all the known risk factors the greatest impact on carotid atherosclerosis in alcoholics was exerted by age, hypertension, LDL cholesterol and fasting plasma glucose levels. Subjects carrying the APO E epsilon4 allele were more liable to develop atherosclerotic changes in carotid arteries compared with subjects with the epsilon3/3 genotype, which showed statistical significance in patients under 50 years of age. No association was shown between ACE I/D polymorphism and carotid atherosclerosis. APO E polymorphism can increase the risk of carotid atherosclerosis development in an alcoholic subject. The association of the APO E epsilon4 allele with carotid atherosclerosis was significant in younger patients. Since the elevated carotid IMT is considered to be a good marker of increased risk of generalized atherosclerosis the consequences could involve both cardiac and cerebrovascular events.
    Alcohol and Alcoholism 04/2005; 40(4):274-82. DOI:10.1093/alcalc/agh157 · 2.09 Impact Factor
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    ABSTRACT: The paper presents current opinions on the mechanism of beta-amyloid accumulation, the role of cholesterol in the pathogenesis of dementia and observations of the role of statins in its development. Most of the observations were done on Alzheimer's disease, some of them concerned also dementia of a vascular origin and cognition. Statins are inhibitors of the cholesterol synthesis pathway. The mechanism of their action concerns not only their influence on the cholesterol level but also their influence on prenylation of various proteins and in consequence inhibition of inflammatory reactions. They exert also antioxidative activity. As the number of prospective studies is still insufficient the question whether statins could be used as drugs against dementia remains still unsolved.
    Neurologia i neurochirurgia polska 01/2005; 39(4):318-23. · 0.54 Impact Factor
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    ABSTRACT: The aim of the work was to recognize whether often observed high levels of apolipoprotein (a) [Lp(a)] in patients shortly after an ischemic stroke are a result of the acute phase reaction. In 13 patients Lp(a) was determined within the first 24 hours after the stroke onset, after the next 7 days and after three months i.e. when it could be considered that Lp(a) level was the same as before onset of the disease. In 17 patients only two determinations were performed. Another acute phase indicator: C-reactive protein (CRP), as well as serum lipids were also determined. CRP level was increased in the first determination and increased further after 7 days. After three months it returned to low values. High density lipoprotein (HDL) cholesterol which demonstrates a negative acute phase response changed in the opposite way. No similar fluctuations of Lp(a) level were observed. It can be concluded that during the investigated period Lp(a) had no properties of the acute phase reactant.
    Neurologia i neurochirurgia polska 01/2004; 38(3):197-200. · 0.54 Impact Factor
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    ABSTRACT: In patients with dementia, 29 diagnosed as probably suffering from Alzheimer's disease and 46 subjects with dementia of vascular origin, and in 41 non demented control subjects LDL oxidation in vitro was compared in carriers of various apolipoprotein E alleles. Restriction isotyping was performed by gene amplification and cleavage with Hhal, LDL oxidation was investigated by determination of conjugated dienes and vitamin E (alpha tocopherol) plasma level was measured by HPLC. In subjects with dementia oxidation of LDL was shown to be higher in carriers of epsilon4 allele as compared with non-carriers of this allele. It was especially observed in the propagation phase, which illustrates oxidation intensity after the exhaustion of the antioxidant reserve in LDL. Vitamin E level did not show differences between carriers of different alleles. It is concluded that the differences in oxidation susceptibility of LDL between demented subjects possessing particular apolipoprotein E forms can result partially from differing antioxidant properties of apolipoprotein E isoforms and, in a substantial degree, from the size and quality of LDL.
    Folia Neuropathologica 02/2003; 41(2):65-8. · 1.67 Impact Factor
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    ABSTRACT: Little is known about the role of antioxidant activity in the pathogenesis of stroke-associated neuronal damage and impairment following a stroke. Increased free radical formation together with reduced antioxidant defense may increase neuronal injury. A low concentration of antioxidants such as alpha-tocopherol may influence the development of post-stroke dementia. The aim of this study was to evaluate the level of alpha-tocopherol and susceptibility of LDL to oxidation in a group of patients with dementia in comparison to controls. In a group of 68 patients with dementia, according to DSM-IV criteria, 42 with vascular dementia (VaD), 26 with Alzheimer type of dementia (AD) and 46 age-matched persons, with no signs of cognitive disorders (control group), we measured lipids, alpha-tocopherol and the kinetics of LDL oxidation. The levels of triglycerides (TG) and low-density lipoprotein (LDL) were significantly lower in patients with VaD in comparison to AD patients, but the atherogenic index was similar in both groups. alpha-Tocopherol was significantly lower in patients with VaD in comparison to patients with AD and controls: 9.9, 12.6 and 12.6 ng/ml, respectively, p<0.0001. Susceptibility of LDL to oxidation, measured by duration of lag phase did not reveal statistically significant differences between the groups. In patients with VaD, low levels of plasma alpha-tocopherol were observed, which indicate a reduced antioxidant defense in these subjects.
    Journal of the Neurological Sciences 11/2002; 203-204:195-7. DOI:10.1016/S0022-510X(02)00290-3 · 2.26 Impact Factor
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    ABSTRACT: The uptake of acetaldehyde-modified (ethylated) low-density lipoproteins (LDLs) by murine peritoneal macrophages is described and compared with the uptake of acetylated LDLs. The fluorescent marker DiI was used. No competition between ethylated and acetylated LDLs was observed. Ethylated LDL uptake was not inhibited by polyinosinic acid or fucoidin. Our conclusion is that uptake of ethylated and acetylated LDLs can be done by two different receptors.
    Alcohol 05/2002; 26(3):163-6. DOI:10.1016/S0741-8329(02)00196-9 · 2.04 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 · 2.44 Impact Factor