Unhealthy aging poses a global challenge with profound healthcare and socioeconomic implications. Slowing down the aging process offers a promising approach to reduce the burden of a number of age-related diseases, such as dementia, and promoting healthy longevity in the old population. In response to the challenge of the aging population and with a view to the future, Norway and the United Kingdom are fostering collaborations, supported by a "Money Follows Cooperation agreement" between the 2 nations. The inaugural Norway-UK joint meeting on aging and dementia gathered leading experts on aging and dementia from the 2 nations to share their latest discoveries in related fields. Since aging is an international challenge, and to foster collaborations, we also invited leading scholars from 11 additional countries to join this event. This report provides a summary of the conference, highlighting recent progress on molecular aging mechanisms, genetic risk factors, DNA damage and repair, mitophagy, autophagy, as well as progress on a series of clinical trials (eg, using NAD+ precursors). The meeting facilitated dialogue among policymakers, administrative leaders, researchers, and clinical experts, aiming to promote international research collaborations and to translate findings into clinical applications and interventions to advance healthy aging.
- MeSH
- demence * prevence a kontrola epidemiologie MeSH
- dlouhověkost MeSH
- lidé MeSH
- senioři MeSH
- stárnutí * MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Norsko MeSH
- Spojené království MeSH
BACKGROUND: Having multiple sleep problems is common in adulthood. Yet, most studies have assessed single sleep variables at one timepoint, potentially misinterpreting health consequences of co-occurring sleep problems that may change over time. We investigated the relationship between multidimensional sleep health across adulthood and mortality. METHODS: Participants from the Midlife in the United States Study reported sleep characteristics in 2004-2006 (MIDUS-2; M2) and in 2013-2014 (MIDUS-3; M3). We calculated a composite score of sleep health problems across 5 dimensions: Regularity, Satisfaction, Alertness, Efficiency, and Duration (higher = more problems). Two separate models for baseline sleep health (n = 5 140; median follow-up time = 15.3 years) and change in sleep health (n = 2 991; median follow-up time = 6.4 years) to mortality were conducted. Cox regression models controlled for sociodemographics and key health risk factors (body mass index, smoking, depressive symptoms, diabetes, and hypertension). RESULTS: On average, 88% of the sample reported having one or more sleep health problems at M2. Each additional sleep health problem at M2 was associated with 12% greater risk of all-cause mortality (hazard ratio [HR] = 1.12, 95% confidence interval [CI] = 1.04-1.21), but not heart disease-related mortality (HR = 1.14, 95% CI = 0.99-1.31). An increase in sleep health problems from M2 to M3 was associated with 27% greater risk of all-cause mortality (HR = 1.27, 95% CI = 1.005-1.59), and 153% greater risk of heart disease mortality (HR = 2.53, 95% CI = 1.37-4.68). CONCLUSIONS: More sleep health problems may increase the risk of early mortality. Sleep health in middle and older adulthood is a vital sign that can be assessed at medical checkups to identify those at greater risk.
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- hypertenze * MeSH
- lidé MeSH
- poruchy spánku a bdění * komplikace epidemiologie MeSH
- rizikové faktory MeSH
- senioři MeSH
- spánek MeSH
- Check Tag
- lidé MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Spojené státy americké MeSH
OBJECTIVE: Refractory epilepsy may have an underlying autoimmune etiology. Our aim was to assess the prevalence of neural autoantibodies in a multicenter national prospective cohort of patients with drug-resistant epilepsy undergoing epilepsy surgery utilizing comprehensive clinical, serologic, and histopathological analyses. METHODS: We prospectively recruited patients undergoing epilepsy surgery for refractory focal epilepsy not caused by a brain tumor from epilepsy surgery centers in the Czech Republic. Perioperatively, we collected cerebrospinal fluid (CSF) and/or serum samples and performed comprehensive commercial and in-house assays for neural autoantibodies. Clinical data were obtained from the patients' medical records, and histopathological analysis of resected brain tissue was performed. RESULTS: Seventy-six patients were included, mostly magnetic resonance imaging (MRI)-lesional cases (74%). Mean time from diagnosis to surgery was 21 ± 13 years. Only one patient (1.3%) had antibodies in the CSF and serum (antibodies against glutamic acid decarboxylase 65) in relevant titers; histology revealed focal cortical dysplasia (FCD) III (FCD associated with hippocampal sclerosis [HS]). Five patients' samples displayed CSF-restricted oligoclonal bands (OCBs; 6.6%): three cases with FCD (one with FCD II and two with FCD I), one with HS, and one with negative histology. Importantly, eight patients (one of them with CSF-restricted OCBs) had findings on antibody testing in individual serum and/or CSF tests that could not be confirmed by complementary tests and were thus classified as nonspecific, yet could have been considered specific without confirmatory testing. Of these, two had FCD, two gliosis, and four HS. No inflammatory changes or lymphocyte cuffing was observed histopathologically in any of the 76 patients. SIGNIFICANCE: Neural autoantibodies are a rare finding in perioperatively collected serum and CSF of our cohort of mostly MRI-lesional epilepsy surgery patients. Confirmatory testing is essential to avoid overinterpretation of autoantibody-positive findings.
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- autoprotilátky MeSH
- epilepsie * epidemiologie chirurgie komplikace MeSH
- lidé MeSH
- magnetická rezonanční tomografie MeSH
- malformace mozkové kůry * komplikace MeSH
- prevalence MeSH
- prospektivní studie MeSH
- refrakterní epilepsie * diagnostické zobrazování chirurgie komplikace MeSH
- retrospektivní studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
OBJECTIVES: It has been reported that job demands affect sleep, but how different levels of job demands affect sleep remains unclear. We examined whether curvilinear relationships exist between job demands and multiple sleep health outcomes. DESIGN: Cross-sectional analyses with linear and quadratic effects, using self-administered survey data. SETTING: A national sample of US adults. PARTICIPANTS: Workers from Midlife in the United States Study (MIDUS2; n = 2927). MEASUREMENTS: The Job Content Questionnaire assessed overall and 5 specific aspects of job demands (intensity, role conflict, work overload, time pressure, and interruptions). Habitual sleep health patterns across 5 dimensions (regularity, satisfaction/quality, daytime alertness, efficiency, and duration) were assessed. Age, sex, race/ethnicity, marital/partnered status, education, job tenure, work hours, body mass index, smoking status, and study sample were covariates. RESULTS: There were significant linear and quadratic relationships between job demands and sleep outcomes. Specifically, the linear effects indicated that participants with higher job demands had worse sleep health, such as shorter duration, greater irregularity, greater inefficiency, and more sleep dissatisfaction. The quadratic effects, however, indicated that sleep regularity and efficiency outcomes were the best when participants' job demands were moderate rather than too low or too high. These effects were found for overall job demands as well as for specific aspects of job demands. Stratified analyses further revealed that these curvilinear associations were mainly driven by participants with low job control. CONCLUSIONS: Moderate levels of job demands, especially if combined with adequate job control, are related to optimal sleep health.
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- dospělí MeSH
- kouření MeSH
- lidé MeSH
- průřezové studie MeSH
- průzkumy a dotazníky MeSH
- psychický stres * MeSH
- spánek * MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Spojené státy americké MeSH
Elevated impulsivity is a key component of attention-deficit hyperactivity disorder (ADHD), bipolar disorder and juvenile myoclonic epilepsy (JME). We performed a genome-wide association, colocalization, polygenic risk score, and pathway analysis of impulsivity in JME (n = 381). Results were followed up with functional characterisation using a drosophila model. We identified genome-wide associated SNPs at 8q13.3 (P = 7.5 × 10-9) and 10p11.21 (P = 3.6 × 10-8). The 8q13.3 locus colocalizes with SLCO5A1 expression quantitative trait loci in cerebral cortex (P = 9.5 × 10-3). SLCO5A1 codes for an organic anion transporter and upregulates synapse assembly/organisation genes. Pathway analysis demonstrates 12.7-fold enrichment for presynaptic membrane assembly genes (P = 0.0005) and 14.3-fold enrichment for presynaptic organisation genes (P = 0.0005) including NLGN1 and PTPRD. RNAi knockdown of Oatp30B, the Drosophila polypeptide with the highest homology to SLCO5A1, causes over-reactive startling behaviour (P = 8.7 × 10-3) and increased seizure-like events (P = 6.8 × 10-7). Polygenic risk score for ADHD genetically correlates with impulsivity scores in JME (P = 1.60 × 10-3). SLCO5A1 loss-of-function represents an impulsivity and seizure mechanism. Synaptic assembly genes may inform the aetiology of impulsivity in health and disease.
- Publikační typ
- časopisecké články MeSH
BACKGROUND AND PURPOSE: N-methyl-d-aspartate receptor (NMDAR) and leucine-rich glioma-inactivated protein 1 (LGI1) encephalitis are important types of autoimmune encephalitis (AE) with significant morbidity. In this study, we used a proteomic approach in search of novel clinically relevant biomarkers in these types of encephalitides. METHODS: Swedish and Czech tertiary neuroimmunology centers collaborated in this retrospective exploratory study. Fifty-eight cerebrospinal fluid (CSF) samples of 28 patients with AE (14 definite NMDAR, 14 with definite LGI1 encephalitis) and 30 controls were included. CSF samples were analyzed using proximity extension assay technology (Olink Target 96 Inflammation panel). For each CSF sample, 92 proteins were measured. Clinical variables were retrospectively collected, and correlations with protein levels were statistically analyzed. RESULTS: Patients and controls differed significantly in the following 18 biomarkers: TNFRSF9, TNFRSF12, TNFRSF14, TNFβ, TNFα, IL7, IL10, IL12B, IFNγ, CD5, CD6, CASP8, MMP1, CXCL8, CXCL10, CXCL11, IL20RA, and sirtuin 2 (SIRT2). In LGI1 encephalitis, no clinically useful association was found between biomarkers and clinical variables. In the NMDAR encephalitis group, SIRT2, TNFβ, and CD5 were significantly associated with ovarian teratoma. For SIRT2, this was true even for the first patients' CSF sample (SIRT2 without vs. with tumor, mean ± SD = 2.2 ± 0.29 vs. 2.88 ± 0.48; p = 0.007, 95% confidence interval = -1.15 to -0.22; r statistic in point-biserial correlation (rpb) = 0.66, p = 0.011). SIRT2 was positively correlated with age (rpb = 0.39, p = 0.018) and total hospital days (r = 0.55, p = <0.001). CONCLUSIONS: SIRT2 should be investigated as a biomarker of paraneoplastic etiology in NMDAR encephalitis.
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- autoprotilátky MeSH
- biologické markery mozkomíšní mok MeSH
- encefalitida s protilátkami proti NMDA receptorům * mozkomíšní mok MeSH
- lidé MeSH
- novorozenec MeSH
- proteomika MeSH
- retrospektivní studie MeSH
- sirtuin 2 MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Idiopathic generalized epilepsy (IGE) is one of the most common epilepsies and is believed to have a strong genetic origin. Patients with IGE present largely heterogeneous neurocognitive profiles and might show some neurocognitive impairments. Furthermore, IGE siblings may demonstrate worse results in neuropsychological tests as well. In our study, we aimed to map the neurocognitive profile both in patients with IGE and the siblings. We also sought to establish a neurocognitive profile for each IGE syndrome. METHODS: The research sample included 110 subjects (IGE n = 46, biological siblings BS n = 16, and healthy controls n = 48) examined. Subjects were neuropsychologically examined in domains of intelligence, attention, memory, executive, and motor functions. The data obtained from the examination were statistically processed to determine whether and how IGE patients (including distinct syndromes) and the siblings differed neurocognitively from healthy controls (adjusted z-scores by age, education, and gender, and composite z-scores of cognitive domains). Data on anti-seizure medication, including defined daily doses, were obtained and included in the analysis. RESULTS: IGE patients and their biological siblings performed significantly worse in most of the neuropsychological tests than healthy controls. The neurocognitive profile of composite z-scores showed that IGE and biological siblings had equally significantly impaired performance in executive functions. IGE group also demonstrated impaired composite attention and motor function scores. The profile of individual IGE syndromes showed that JAE, JME, and EGTCS had significantly worse performance in composite execution score and motor function score. JAE presented significantly worse performance in intelligence and attention. JME exhibited significantly worse composite score in the attention domain. Anti-seizure medication, depression, and quality of life were unrelated to cognitive performance in IGE group. The level of depression significantly predicted the overall value of quality of life in patients with IGE, while cognitive domains, sociodemographic, and clinical factors were unrelated. CONCLUSION: Our study highlights the importance to consider the neurocognitive profile of IGE patients that can lead to difficulties in their education, acceptance, and management of coping strategies. Cognitive difficulties of IGE siblings could support a hypothesis that these impairments emerge from heritable traits.
- MeSH
- epilepsie generalizovaná * MeSH
- imunoglobulin E MeSH
- kvalita života MeSH
- lidé MeSH
- neuropsychologické testy MeSH
- sourozenci * psychologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Cochlear implantation (CI) is associated with changes in the histopathology of the inner ear and impairment of vestibular function. OBJECTIVE: The objectives of our study were to evaluate patients for clinical manifestations of space perception and balance changes before surgery, compare them with asymptomatic subjects (controls), and report changes in posturography and subjective visual vertical (SVV) during the acute post-surgery period in patients. METHODS: Examination was performed using static posturography and the SVV measurement. We examined 46 control subjects and 39 CI patients. Patients were examined pre-surgery (Pre), 2nd day (D2) and then 14th day (D14) after implantation. RESULTS: Baseline SVV was not different between patients and control group. There was a statistically significant difference (p < 0.001) in SVV between subgroups of right- and left-implanted patients at D2 (-1.36±3.02° and 2.71±2.36°, right and left side implanted respectively) but not Pre (0.76±1.07° and 0.31±1.82°) or D14 (0.72±1.83° and 1.29±1.60°). Baseline posturography parameters between patients and control group were statistically significantly different during stance on foam with eyes closed (p < 0.05). There was no statistically significant difference in posturography among Pre, D2 and D14. CONCLUSIONS: CI candidates have impaired postural control before surgery. CI surgery influences perception of subjective visual vertical in acute post-surgery period with SVV deviation contralateral to side of cochlear implantation, but not after two weeks.
- MeSH
- kochleární implantace * MeSH
- lidé MeSH
- posturální rovnováha MeSH
- vestibulární aparát * MeSH
- vnímání prostoru MeSH
- zraková percepce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
