Restless Legs Syndrome and All-Cause Mortality in Four Prospective Cohort Studies

Objectives: To evaluate the association between restless legs syndrome (RLS) and all-cause mortality. Design: Four prospective cohort studies. Setting: The Dortmund Health Study (DHS) and the Study of Health in Pomerania (SHIP) from Germany. The Women's Health Study (WHS) and the Physicians’ Health Study (PHS) from the USA. Participants: In DHS: a random sample (n=1 299) from the population of Dortmund; in SHIP: a sample (n=4 291) from residents living in West Pomerania were drawn by multistage random sampling design; in WHS: female healthcare professionals (n=31 370); in PHS: male physicians (n=22 926) Main outcome measures: All-cause mortality. Results: The prevalence of RLS ranged between 7.4% and 11.9% at baseline. During follow-up (ranging between 6 and 11 years) RLS was not associated with increased risk of all-cause mortality in any of the four cohorts. The multivariable-adjusted HRs (95% CI) for all-cause mortality ranged from 0.21 (0.03 to 1.53) to 1.07 (0.93 to 1.23) across the four studies. The HRs for all-cause mortality did not differ according to gender. Conclusions: In these four independently conducted large prospective cohort studies from Germany and the USA, RLS did not increase the risk of all-cause mortality. These findings do not support the hypothesis that RLS is a risk factor for mortality of any cause

AMP-activated kinase (AMPK) activation by AICAR in human white adipocytes derived from pericardial white adipose tissue stem cells induces a partial beige-like phenotype

Beige adipocytes are special cells situated in the white adipose tissue. Beige adipocytes, lacking thermogenic cues, morphologically look quite similar to regular white adipocytes, but with a markedly different response to adrenalin. White adipocytes respond to adrenergic stimuli by enhancing lipolysis, while in beige adipocytes adrenalin induces mitochondrial biogenesis too. A key step in the differentiation and function of beige adipocytes is the deacetylation of peroxisome proliferator-activated receptor (PPARγ) by SIRT1 and the consequent mitochondrial biogenesis. AMP-activated protein kinase (AMPK) is an upstream activator of SIRT1, therefore we set out to investigate the role of AMPK in beige adipocyte differentiation using human adipose-derived mesenchymal stem cells (hADMSCs) from pericardial adipose tissue. hADMSCs were differentiated to white and beige adipocytes and the differentiation medium of the white adipocytes was supplemented with 100 μM [(2R,3S,4R,5R)-5-(4-Carbamoyl-5-aminoimidazol-1-yl)-3,4-dihydroxyoxolan-2-yl]methyl dihydrogen phosphate (AICAR), a known activator of AMPK. The activation of AMPK with AICAR led to the appearance of beige-like morphological properties in differentiated white adipocytes. Namely, smaller lipid droplets appeared in AICAR-treated white adipocytes in a similar fashion as in beige cells. Moreover, in AICAR-treated white adipocytes the mitochondrial network was more fused than in white adipocytes; a fused mitochondrial system was characteristic to beige adipocytes. Despite the morphological similarities between AICAR-treated white adipocytes and beige cells, functionally AICAR-treated white adipocytes were similar to white adipocytes. We were unable to detect increases in basal or cAMP-induced oxygen consumption rate (a marker of mitochondrial biogenesis) when comparing control and AICAR-treated white adipocytes. Similarly, markers of beige adipocytes such as TBX1, UCP1, CIDEA, PRDM16 and TMEM26 remained the same when comparing control and AICAR-treated white adipocytes. Our data point out that in human pericardial hADMSCs the role of AMPK activation in controlling beige differentiation is restricted to morphological features, but not to actual metabolic changes

Lack of Association Between Shape and Volume of Subcortical Brain Structures and Restless Legs Syndrome

ObjectivePrevious studies on patients with restless legs syndrome (RLS) yielded inconclusive results in the magnetic resonance imaging (MRI)-based analyses of alterations of subcortical structures in the brain. The aim of this study was to compare volumes as well as shapes of subcortical structures and the hippocampus between RLS cases and controls. Additionally, the associations between the genetic risks for RLS and subcortical volumes were investigated.MethodsWe compared volumetric as well as shape differences assessed by 3 T MRI in the caudate nucleus, hippocampus, globus pallidus, putamen, and thalamus in 39 RLS cases versus 117 controls, nested within a population-based sample. In a subsample, we explored associations between known genetic risk markers for RLS and the volumes of the subcortical structures and the hippocampus.ResultsNo significant differences between RLS cases and controls in subcortical and hippocampal shapes and volumes were observed. Furthermore, the genetic risk for RLS was unrelated to any alterations of subcortical and hippocampal gray matter volume.InterpretationWe conclude that neither RLS nor the genetic risk for the disease give rise to changes in hippocampal and subcortical shapes and gray matter volumes

The relationship between Alzheimer's-related brain atrophy patterns and sleep macro-architecture

Introduction Sleep is increasingly recognized as a major risk factor for neurodegenerative disorders such as Alzheimer's disease (AD). Methods Using an magnetic resonance imaging (MRI)–based AD score based on clinical data from the Alzheimer's Disease Neuroimaging Initiative 1 (ADNI1) case-control cohort, we investigated the associations between polysomnography-based sleep macro-architecture and AD-related brain atrophy patterns in 712 pre-symptomatic, healthy subjects from the population-based Study of Health in Pomerania. Results We identified a robust inverse association between slow-wave sleep and the AD marker (estimate: −0.019; 95% confidence interval: −0.03 to −0.0076; false discovery rate [FDR] = 0.0041), as well as with gray matter (GM) thicknesses in typical individual cortical AD-signature regions. No effects were identified regarding rapid eye movement or non–rapid eye movement (NREM) stage 2 sleep, and NREM stage 1 was positively associated with GM thickness, mainly in the prefrontal cortical regions. Discussion There is a cross-sectional relationship between AD-related neurodegenerative patterns and the proportion of sleep spent in slow-wave sleep