BDNF Val66Met polymorphism is associated with consolidation of episodic memory during sleep.

The brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, a candidate neurobiological mechanism underlying learning and memory. A functional polymorphism in the BDNF gene, Val66Met (rs6265), has been linked to memory and cognition in healthy individuals and clinical populations. Sleep contributes to memory consolidation, yet information about the possible role of BDNF in this process is scarce. To address this question, we investigated the relationship between the BDNF Val66Met genotype and consolidation of episodic declarative and procedural (motor) non-declarative memories in healthy adults. The carriers of Met66 allele, as compared with Val66 homozygotes, showed stronger forgetting overnight (24 h after encoding), but not over shorter time (immediately or 20 min after word list presentation). There was no effect of Val66Met genotype on motor learning. These data suggest that BDNF plays a role in neuroplasticity underlying episodic memory consolidation during sleep.

Association of HTTLPR, BDNF, and FTO Genetic Variants with Completed Suicide in Slovakia.

Since suicide and suicidal behavior are considered highly heritable phenotypes, the identification of genetic markers that can predict suicide risk is a clinically important topic. Several genes studied for possible associations between genetic polymorphisms and suicidal behaviors had mostly inconsistent and contradictory findings. The aim of this case-control study was to evaluate the associations between completed suicide and polymorphisms in genes BDNF (rs6265, rs962369), SLC6A4 (5-HTTLPR), and FTO (rs9939609) in relation to sex and BMI. We genotyped 119 completed suicide victims and 137 control subjects that were age, sex, and ethnicity matched. A significant association with completed suicide was found for BDNF rs962369. This variant could play a role in completed suicide, as individuals with the CC genotype were more often found among suicides than in control subjects. After sex stratification, the association remained significant only in males. A nominally significant association between the gene variant and BMI was observed for BDNF rs962369 under the overdominant model. Heterozygotes with the TC genotype showed a lower average BMI than homozygotes with TT or CC genotypes. FTO polymorphism (rs9939609) did not affect BMI in the group of Slovak suicide completers, but our findings follow an inverse association between BMI and completed suicide.

Assessment of Automatic and Controlled Retrieval Using Verbal Fluency Tasks.

Category and letter verbal fluency assessment is widely used in basic and clinical research. Yet, the nature of the processes measured by such means remains a matter of debate. To delineate automatic (free-associative) versus controlled (dissociative) retrieval processes involved in verbal fluency tasks, we carried out a psychometric study combining a novel lexical-semantic retrieval paradigm and structural equation modeling. We show that category fluency primarily engages a free-associative retrieval, whereas letter fluency exerts executive suppression of habitual semantic associates. Importantly, the models demonstrated that this dissociation is parametric rather than absolute, exhibiting a degree of unity as well as diversity among the retrieval measures. These findings and further exploratory analyses validate that category and letter fluency tasks reflect partially distinct forms of memory search and retrieval control, warranting different application in basic research and clinical assessment. Finally, we conclude that the novel associative-dissociative paradigm provides straightforward and useful behavioral measures for the assessment and differentiation of automatic versus controlled retrieval ability.

Evaluation of 5-HTTLPR (insertion/deletion) and BDNF (rs6265) genetic variations in the Slovakian individuals suffering from affective disorders.

The pathophysiology of affective disorders (AD), including depressive disorders (DD) and anxiety disorders (ANXD), is still unclear. To understand risk factors of the disorders, we evaluated genetic variations of the serotonin reuptake transporter (5-HTTLPR, ins/del) and the brain-derived neurotrophic factor (BDNF, rs6265) in Slovak patients suffering from AD. After genotyping we observed a significantly increased frequency of LS and LL genotypes (5-HTTLPR) in individuals diagnosed with AD compared to controls (OR = 1.99, 95% CI = 1.21-3.27, p = 0.006). There was also a significant relationship between TT (BDNF) genotype and the risk of AD in males (OR = 5.93, 95% CI = 1.42-27.07, p = 0.011). In gene-gene analysis, the LL or LS (5-HTTLPR) and CT or TT (BDNF) genotype combinations had a risk-enhancing effect on AD susceptibility (mainly ANXD in males), while SS (5-HTTLPR) and TT (BDNF) combination had a protective effect on AD risk (mainly ANXD). However, larger prospective studies are needed to confirm our findings.

Which clinical and neuropsychological factors are responsible for cognitive impairment in patients with epilepsy?

OBJECTIVES: The study aimed to assess the effect of demographic and clinical features of epilepsy, anxiety, depressed mood, sleep, and quality of life on the prediction of cognitive decline in patients with epilepsy. METHODS: Two hundred and six consecutive patients with epilepsy (age 41.8 ± 15.6 years, mean, SD) out of 279, were included in this cross-sectional study. We used simple linear regression to calculate the results. RESULTS: Objective cognitive status was predicted by anxiety and depression mood changes (Beck Anxiety Inventory (BAI), p = 0.03, Beck Depression Inventory (BDI), p = 0.005), language subdomain of Quality of Life Inventory in Epilepsy-89 (QOLIE-89) (p = 0.003), and total QOLIE-89 (p = 0.001). No significance was shown in demographic and clinical features of epilepsy (gender, age at onset, epilepsy duration, type, etiology of epilepsy, and antiepileptic treatment), except frequency of generalized epileptic seizures (p = 0.03), which also served as an independent predictor of anxiety (BAI) and depression (BDI). CONCLUSIONS: Our findings point at the role of mood changes in the cognitive status of patients with epilepsy, which should be used as an essential therapeutic target apart of seizure control.

Narcolepsy in Slovakia - Epidemiology, clinical and polysomnographic features, comorbid diagnoses: a case-control study.

OBJECTIVE: An increase in the incidence of narcolepsy after the pandemic influenza with the H1N1 vaccination in 2009 resulted in an interest in narcolepsy epidemiology. The aim of the study was to examine the incidence and prevalence rates of narcolepsy and to describe the associated characteristics in Slovakia. METHODS: Epidemiology data were calculated for each year from 2000 to 2017 based on records found in specialized centres. In sum, 61 narcoleptic patients were diagnosed, of which 51 (84%) had narcolepsy type 1 (NT1). Clinical data and results of polysomnography (PSG), Human Leukocyte Antigen (HLA)-typing, hypocretin (HCRT)-1 levels and body mass index (BMI) were summarised and evaluated for NT1 and narcolepsy type2 (NT2). Later, 244 sex and age matched controls were chosen to evaluate the comorbid diagnoses. RESULTS: The prevalence of narcolepsy in 2017 in Slovakia was 10.47 (CI 95% 8.26-14) cases/million inhabitants, and the mean incidence rate (2000-2017) was 0.57 (CI 95% 0.4-0.74) cases/million inhabitants. Narcoleptic patients were comorbid with arterial hypertension (17%), ischemic heart disease (8%), dyslipidaemia (18%), diabetes mellitus type 2 (10%), cardiac arrhythmia/atrial fibrillation (5%), autoimmune disorders (20%), allergy (11%), malignancy (3%), headache (15%) and mental disorders (20%). Patients with narcolepsy showed double the excess prevalence in mental disorders (OR 2.15, p < 0.05), and dyslipidaemia (OR 2.22, p < 0.05). The presence of autoimmune disorders and allergy showed a mild increase in the narcolepsy group (OR 1.46, resp. 1.63). Hashimoto thyroiditis (HT) was the most frequent autoimmune disorder. CONCLUSIONS: Narcolepsy is a rare disorder in Slovakia. From the phenotype, genetic characteristics and comorbidities the disorder does not vary from other European countries.

The insomnia phenotype in genetic Creutzfeldt-Jakob disease based on the E200K mutation.

The aim of the presented study was to reveal the frequency of insomnia spells in E200K genetic Creutzfeldt-Jakob disease (gCJD) patients. Clinical records of 22 subjects diagnosed with E200K gCJD were retrospectively reviewed. The patients w/wo insomnia (n = 4, 18%/n = 18, 82%) did not differ in age, sex and the duration of the symptomatic phase. Analysis of the clinical features in the groups yielded differences in the clinical signs in the early phase of the disorder, proportion of homozygotes (Met/Met) at codon 129, MRI changes in the thalamus and the typical EEG abnormality. The study suggests that apart from traditional clinical features, the insomnia is not a rare early symptom in phenotype of E200K gCJD based on early thalamic involvement.

Development of Regional Disparities in Alzheimer's Disease Mortality in the Slovak Republic from 1996 to 2015.

Alzheimer's disease-subsequently as AD in the text-represents a chronic neurodegenerative disease discussed very often in the recent period. It involves the G30 diagnosis expressing exactly AD and also the F00 diagnosis epitomising dementia in AD. The Slovak Republic has a very various population in terms of the disparities of the population localisation. The analysis is executed on the basement of the standardised mortality rate. It is calculated for the individual districts of the Slovak Republic to get a detailed spatial view and for each year of the explored period from 1996 to 2015 to get a time development. It has a considerably rising tendency. Therefore, the regional disparities of the standardised mortality rate of AD are analysed from an angle of view of its similarity, by its measurement in a form of a Euclidean distance approach. The results of the analysis offer the heat maps as the distance matrices in a graphic form and the maps of the individual districts too. These outputs reveal a very heterogeneous structure of the standardised mortality rate. Another graphic outcome demonstrates a distribution of its values among the districts throughout the whole Slovak Republic for the whole observed period. The results offer a comparison among the districts of the Slovak Republic too. The highest values and also the lowest values are reached in the different districts for the both sexes. Even, one district reaches the opposite result for the individual sexes. The age structure of the deceased population on the G30 diagnosis is also executed and the extreme values from an angle of a view of the districts are picked up. There are evident high differentiations between the individual districts of the Slovak Republic. The conclusion section involves the several key points and the potential suggestions for further research.

Creutzfeldt-Jakob disease surveillance in Eastern Slovakia from 2004 to 2016.

OBJECTIVES: An extraordinary incidence of genetic Creutzfeldt-Jakob disease (gCJD) appearing in clusters in the Slovak Republic was described in the 1990's. The aim of the study was to analyse data of CJD cases obtained from surveillance in Eastern Slovakia (ES) (2004-2016), the region outside the described geographical clusters. METHODS: The database set in the project was the source for epidemiological and clinical analysis of CJD cases. RESULTS: The incidence of CJD in ES (2004-2016) was 1.7/million person-years (95% CI 1-2.4); the incidence increase in the last five years (2012-2016) was comparable to the whole country. Twenty seven of 29 reported CJD cases were available for analysis (mean age 59 years, F/M 15/12). The proportion of gCJD (E200K mutation) cases remained dominant (78%), with 9 familiar cases originating in 4 families. Analysis of the clinical features revealed shorter duration of the symptomatic phase in sporadic CJD (sCJD) (3.4 months) versus gCJD (5.15 months). Cognitive/behavioural changes, insomnia, and sensory disturbance were more pronounced in the early symptoms of gCJD. Periodic EEG discharges were more frequent in sCJD (83%) than gCJD (56%), all 19 available MR findings were CJD specific and localisation of abnormalities varied amongst the CJD forms. CONCLUSIONS: The surveillance of CJD in ES (2004-2016) showed an increased incidence of CJD in ES, reaching the incidence rate of the whole country, with a permanent proportion of 70% gCJD cases based on the E200K mutation. Clinical, electrophysiological and MR features of sCJD and gCJD cases were in conformity with already published data. Epidemiological analysis of CJD in ES shows increasing detection of CJD but also suggests that current routine surveillance systems for CJD may underestimate the true burden of disease, especially sporadic cases in Slovakia.

Prevalence of Prodromal Parkinson's Disease as Defined by MDS Research Criteria among Elderly Patients Undergoing Colonoscopy.

BACKGROUND: Gastrointestinal symptoms are a well-recognized and common premotor feature of Parkinson's disease (PD). Moreover, multiple studies have assessed the value of colonic α-synuclein as a potential marker of prodromal PD. Recently, the International Parkinson and Movement Disorders Society (MDS) defined research criteria for prodromal PD. OBJECTIVE: The aim of our study was to test the MDS research criteria in patients undergoing diagnostic colonoscopies as potential candidates for inclusion in prospective trials evaluating colonic biopsies as a potential biomarker of prodromal PD. METHODS: We evaluated elderly patients without manifest parkinsonism undergoing diagnostic colonoscopies. During the study we assessed all risks and prodromal markers of the MDS research criteria, excluding radiotracer imaging and genetic testing. RESULTS: The mean age of the 100 enrolled patients was 61.6±9.7 years; 42 were men. The most common prodromal marker in our cohort was constipation (40%), followed by MDS-UPDRS part III scores of >6 points, excluding action tremor items (39%) and hyposmia (37%). Substantia nigra hyperechogenicity was identified in 9%, and polysomnography confirmed REM sleep behavior disorder in 2% of the patients. Five of the 100 enrolled patients (5%) fulfilled the criteria for probable prodromal PD, while another 3 patients met the 50% probability threshold. CONCLUSIONS: Our findings suggest, that the prevalence of prodromal PD in patients undergoing diagnostic colonoscopies may be higher compared to the general elderly population, although this should be confirmed in further studies including also matched controls not undergoing colonoscopy. The real prevalence of prodromal PD in this cohort will have to be confirmed in longitudinal follow-up. Patients undergoing diagnostic colonoscopies may be good candidates for multistep screening and inclusion in prospective trials.