Volume changes of medial temporal lobe structures in patients with genetic generalized and temporal lobe epilepsy in relation to neuropsychological functions.

Purpose: In patients with epilepsy (PWE), cognitive and behavioural dysfunctions are associated with abnormalities in various brain areas. The aim of the study was to compare the volume of the hippocampus (VHIP), amygdala (VAMG) and parahippocampal gyrus (VPHG) with the results of neuropsychological assessment in patients with temporal lobe epilepsy (TLE) and genetic generalized epilepsy (GGE). Methods: 33 PWE were enrolled in the study (mean age 37.3), 10 with TLE and 23 GGE (12 with GGE with tonic-clonic seizure [GGE-GTCS], and 11 with juvenile myoclonic epilepsy). 19 healthy persons (mean age 32.2) were enrolled as the control group (CG). Measurements of VHIP, VAMG and VPHG were made with 3D completely balanced steady state (CBASS) and 3D T1-weighted sequence. All participants underwent a neuropsychological assessment using a multi-domain cognitive battery and emotional state questionnaires. Results: The left hippocampus was significantly smaller in patients with left TLE (LTLE) and with GGE-GTCS, compared to the CG (p = 0.0069). In LTLE a significant enlargement of the right amygdala in comparison to the CG and other types of epilepsy were found (p = 0.0015). Among patients with LTLE and GGE-GTCS, impairment of attention and executive functions was statistically more common than in the CG. VHIP right (r = 0.25 p < 0.01) and VHIP left (r = 0.26 p < 0.04) were positively correlated with phonetic verbal fluency. Conclusions: PWE showed changes in the volume of selected medial temporal lobe (MTL) structures. Selective impairment of attention and executive functions was found. Some neuropsychological findings correlate with volume changes in MTL structures. Antiseizure medications therapy could have an impact on the severity of neuropsychological dysfunctions.

The prevalence of depressive and anxiety symptoms in Polish epilepsy patients - The context of pharmaco-resistance.

PURPOSE: Patients with epilepsy (PWE) are at a higher risk of experiencing depressive and anxiety symptoms than the general population; these symptoms are more prevalent in patients with drug-resistant epilepsy (DRE) compared to those with non-drug-resistant epilepsy (NDRE). The aim of the present study was to compare the level of reported depressive and anxiety symptoms in patients with DRE and patients with NDRE and to examine the relationships between demographic and epilepsy-related variables and severity of depression and anxiety symptoms. MATERIAL AND METHODS: A total of 193 adult PWE, divided into a DRE group (n = 87), and an NDRE group (n = 106), completed the Beck Depression Inventory (BDI) and the Stat-Trait Anxiety Inventory (STAI-Sand STAI-T). Data analysis included sociodemographic and disease-related variables such as the type of epilepsy syndrome, age at onset of disease, and duration of the disease. RESULTS: The DRE group presented a higher score of BDI than the NDRE group (p = 0.04). Age correlated with the score of STAI-S in the NDRE group (r = 0.22). Sex was the only significant predictor of the score of STAI-T in the NDRE group. Men from the DRE group presented higher scores in BDI, STAI-S, and STA-T compared with the NDRE group. CONCLUSIONS: Patients with DRE reported more severe depressive symptoms than patients with NDRE. In NDRE patients, the level of anxiety, considered as a state, was correlated with age. Sex was a significant predictor of the level of anxiety in DRE patients. Pharmaco-resistance was significantly associated with severity of depression and anxiety in male patients.

Association of adiponectin, leptin and resistin with inflammatory markers and obesity in dementia.

The aim of the study was to determine the role of adiponectin, leptin and resistin in various types of dementia and to investigate their association with inflammatory markers, insulin resistance and abdominal obesity. In 205 patients with dementia [89 with Alzheimer's disease (AD), 47 with vascular dementia (VaD), 69 with mixed dementia (MD)], 113 persons with mild cognitive impairment and in 107 controls serum adiponectin, leptin and resistin levels, pro-inflammatory [interleukin-6 (IL-6), C-reactive protein (hsCRP) and chitotriosidase] and anti-inflammatory (25-OH vitamin D, HDL-cholesterol and paraoxonase 1) markers, as well as glucose metabolism parameters (glucose, insulin and HOMA-IR) were determined. In all-cause dementia adiponectin and resistin levels were significantly higher as compared to the controls; leptin levels did not show differences. Higher adiponectin levels concerned AD and MD, whereas higher resistin-VaD and MD. After stratification by abdominal obesity the differences in adiponectin levels remained significant in subjects without obesity. In all-cause dementia negative correlation of adiponectin with obesity, glucose metabolism parameters, IL-6 and hsCRP and positive correlation with HDL-cholesterol were found. Positive correlation of resistin with age, IL-6, hsCRP and chitotriosidase and negative correlation with HDL-cholesterol and paraoxonase 1 were stated. We conclude that dementia of neurodegenerative origin is characterized by elevated adiponectin levels, whereas dementia with vascular changes by increase of resistin. Association with inflammatory indicators may suggest the pro-inflammatory role of resistin in the development of dementia, especially in dementia of vascular mechanism. Identification of this novel biomarker may be important in preventing dementia.

Homocysteine metabolism and the associations of global DNA methylation with selected gene polymorphisms and nutritional factors in patients with dementia.

Epigenetics (particularly DNA methylation) together with environmental and genetic factors, are key to understanding the pathogenesis of many diseases including dementia. Disturbances in DNA methylation have already been implicated in dementia. Homocysteine metabolism, with folate and vitamin B12 as essential cofactors, is integral to methylation processes. We evaluated in a case-control study the association of global DNA methylation, homocysteine, folate and vitamin 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 non-demented controls consisted of 45 age-matched subjects without dementia and 47 individuals with mild cognitive impairment. Global DNA methylation was determined by Imprint Methylated DNA Quantification Kit MDQ1 (Sigma-Aldrich, Gillingham, Dorset, UK). Plasma homocysteine, serum folate and vitamin B12 were determined by chemiluminescence. Plasma and erythrocyte 5-methyltetrahydrofolate and plasma methylmalonic acid (markers of folate and vitamin B12 status) were measured by HPLC. APOE, PON1 p.Q192R, MTHFR 677C>T (c.665C>T) and IL1B-511C>T polymorphisms were identified using PCR-RFLP methods. Patients with dementia had significantly higher concentrations of homocysteine (p=0.012) and methylmalonic acid (p=0.016) and lower folate (p=0.002) and plasma 5-methyltetrahydrofolate (p=0.005) than non-demented subjects. There was no difference in DNA methylation between patients and controls. A non-significant tendency to higher DNA methylation in patients with vascular dementia (p=0.061) was observed. Multivariate regression analysis of all recruited individuals demonstrated a significant positive association between DNA methylation and folate (p=0.013), creatinine (p=0.003) concentrations and IL1B-511T (p=0.002) and PON1 192R (p=0.049) alleles and negative association with fasting glucose (p=0.004). The biochemical results showed significantly lower folate and vitamin B12 status in demented patients than controls. Global DNA methylation was associated with markers of folate status, creatinine, glucose and PON1 and IL1B polymorphisms.

Correlations between cerebellar and brain volumes, cognitive impairments, ApoE levels, and APOE genotypes in patients with AD and MCI.

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.

Paraoxonase 1 (PON1) gene-108C>T and p.Q192R polymorphisms and arylesterase activity of the enzyme in patients with dementia.

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.

Positive correlation of paraoxonase 1 (PON1) activity with serum insulin level and HOMA-IR in dementia. A possible advantageous role of PON1 in dementia development.

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.

The effect of vitamin B supplementation on homocysteine metabolism and clinical state of patients with chronic epilepsy treated with carbamazepine and valproic acid.

PURPOSE: To investigate the influence of vitamin B supplementation on the plasma total homocysteine (p-tHcy), serum folate (s-FA), serum B12 (s-B12), and clinical state of patients with chronic epilepsy. METHODS: Beck Depression Inventory (BDI) scores and p-tHcy, s-B12, and s-FA levels were assessed at baseline, after 1 year of supplementation (G1), and before and after 1 year of VPA or CBZ therapy (G2). RESULTS: Eighty-one patients participated in the study: 51 patients with chronic epilepsy (G1) treated with carbamazepine (CBZ) or valproic acid (VPA), and 30 patients with newly diagnosed epilepsy (G2). At baseline, mean p-tHcy level was significantly higher in G1 than G2 (p=0.0001) with no significant differences in s-FA or s-B12 levels. p-tHcy level significantly decreased in CBZ-treated G1 patients (p=0.00002) after 1 year of supplementation and increased in G2 after 1 year of anti-epileptic drug (AED) therapy without supplementation. BDI scores in G1 decreased significantly after 1 year of supplementation (p=0.0001) and increased significantly in VPA-treated G2 patients after 1 year of AED therapy (p=0.02). The number of hyperhomocysteinemic patients significantly decreased in G1 after vitamin B supplementation (p=0.01) and increased in G2 (p=0.002). We also observed improved BDI scores and reduced seizure frequency in patients with chronic epilepsy. CONCLUSIONS: These data support the hypothesis that AEDs play a major role in hyperhomocysteinemia development in patients with epilepsy. Adding folate and vitamin B12 to AED therapy is a safe and inexpensive way to reduce the risk of hyperhomocysteinemia.

Predictors of depressive symptoms in patients with stroke - a three-month follow-up.

BACKGROUND AND PURPOSE: Depression is one of the most common post-stroke complications, which could impair rehabilitation outcome and quality of life, and could also increase mortality after stroke. The aim of the present study was to assess the association between demographic, socioeconomic and clinical (stroke risk factors, type of stroke, location of vascular lesion, cognitive functions) factors on the presence and severity of post-stroke depressive symptoms in patients after first ever stroke as well as on their social functioning. MATERIAL AND METHODS: A prospective, cohort study with a three-month observation period was performed in seven centres. Severity of depressive symptoms was assessed with the help of a short, 15-item version of the Geriatric Depression Scale (GDS), 3 months after stroke onset. RESULTS: On the basis of GDS (GDS L 5 points or > 5 points) patients were allocated to a group without (n = 160) or with symptoms suggestive of depression (n = 82). The study groups did not differ with respect to age, sex or place of residence. Univariate logistic regression analysis showed that independent predictors for the presence of symptoms suggestive of depression at 3 months after stroke were: low level of education, low income, greater severity of stroke, worse functional status, self-reported problems with daily-living activities and need of help in daily living activities. More than 60% of patients with depressive symptoms limited their social contacts. Patients with depressive symptoms were unsatisfied with their relations with life partners and friends. CONCLUSIONS: Our study showed a complex aetiology of post-stroke depressive symptoms with an important role of socioeconomic factors. Depressive symptoms after stroke worsen existing health, social and economic problems, and cause social isolation of patients.

Vascular and biochemical risk factors of vascular dementia after lacunar strokes (S-VaD) and after multiinfarcts in strategic areas (M-VaD).

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.

Antibodies against oxidized LDL and apolipoprotein E polymorphism in demented patients.

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.

Paraoxonase activity and dementia.

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.

[The effect of rivastigmine on cognitive functions and regional cerebral blood flow in Alzheimer's disease and vascular dementia: follow-up for 2 years]. / Wplyw riwastygminy na funkcje poznawcze i regionalny przeplyw mózgowy w chorobie Alzheimera i w otepieniu naczyniopochodnym -- dwuletnia obserwacja chorych.

BACKGROUND AND PURPOSE: The aim of the work was to investigate the effect of treatment with rivastigmine, one of the inhibitors of acetylcholinesterase (AChE-I) on the regional cerebral perfusion (rCBF) and the cognitive functions of the brain in patients with Alzheimer's Disease (AD) and Vascular Dementia (VaD). MATERIAL AND METHODS: The investigations of rCBF were carried out using SPECT (Single Photon Emission Computed Tomography). The results given concern investigations of patients carried out at the onset of the investigation, after 12 months, and 24 months of rivastigmine treatment. RESULTS: In patients with AD it was found that treatment with rivastigmine increases rCBF by 5-7% in the temporal areas during the first 12 months. In the frontal areas the increase was by 3-5%. During the next 12 months rCBF with an accuracy of 2% returned to the initial level, with the exception of the motor cortex, where it remained on the level increased by 5-6%. However, the cognitive functions remained constant during the first 12 months of treatment and decreased significantly during the next 12 months. In patients with VaD rCBF increased in all the regions of the brain except for the temporal posterior regions, and remained at an elevated level for the next 12 months. The cognitive functions deteriorated slowly, but to a much lesser degree than in the case of AD. CONCLUSIONS: From the investigations carried out it follows that treatment with rivastigmine during 24 months prevents a decrease of rCBF in patients with AD. However, the cognitive functions deteriorate after 24 months.

The effect of cholinesterase inhibitors on the regional blood flow in patients with Alzheimer's disease and vascular dementia.

The effects of therapy with cholinesterase inhibitors (ChE-I) on regional cerebral blood flow (rCBF) disturbances were investigated by means of single photon emission computed tomography (SPECT). The changes in rCBF were compared with the results of the medical examination and neuropsychological tests. The sample consisted of 41 patients with the Alzheimer's dementia (AD) and vascular dementia (VaD). The effect of ChE-I (rivastigmine) treatment was studied on 33 patients, while the nontreated control group consisted of 8 patients. In the treated patients, an increase in the rCBF was observed, while the scores of the neuropsychological tests decreased slightly. In the VaD group, the increase in rCBF was more significant in the frontal regions, whereas in the group with AD in the temporal regions, respectively. In the nontreated patients, a decrease of both rCBF and scores of neuropsychological tests were observed. The scores of the neuropsychological tests correlated with the results of rCBF. Increased levels of acetylcholine in the brain after ChE-I treatment may support the cholinergic regulation of rCBF, and in result increase it. Such effects seem to be more pronounced in the more affected brain regions.

[Progressive atrophy of the globus pallidus--case report]. / Postepujacy zanik galki bladej--opis przypadku.

The authors report a case of atrophy of the globus pallidus in a woman aged 25 years, diagnosed alive. The diagnosis was based to a large extent on MRI findings. Atrophy of the globus pallidus (AGP) is a rare disease, recognized mostly in neuropathological examination. Its etiopathogenesis has not been explained so far. Since no specific abnormalities have been detected in laboratory tests, the clinical diagnosis of AGP is only probable. However, AGP should be suspected if such extrapyramidal symptoms are present as dystonia, choreoathetosis, muscular rigidity, and characteristic localisation of lesions in MRI. At present only comprehensive symptomatic treatment is possible.