Sleep apnea prevalence in chronic kidney disease - association with total body water and symptoms

Background: Sleep apnea is common and associated with poor outcome in severe chronic kidney disease, but validated screening tools are not available. Our objectives were to determine the prevalence of sleep apnea in this population, to assess the validity of screening for sleep apnea using an ApneaLink device and to investigate the relationship of sleep apnea to; symptoms, spirometry and body water. Methods: Patients with glomerular filtration rate ≤30 mL/min/1.73 m2, whether or not they were receiving haemodialysis, were eligible for enrolment. Participants completed symptom questionnaires, performed an ApneaLink recording and had total body water measured using bioimpedance. This was followed by a multi-channel polysomnography recording which is the gold-standard diagnostic test for sleep apnea. Results: Fifty-seven participants were enrolled and had baseline data collected, of whom only 2 did not have sleep apnea. An apnea hypopnea index ≥30/h was found in 66% of haemodialysis and 54% of non-dialysis participants. A central apnea index ≥5/h was present in 11 patients, with only one dialysis patient having predominantly central sleep apnea. ApneaLink underestimated sleep apnea severity, particularly in the non-dialysis group. Neither total body water corrected for body size, spirometry, subjective sleepiness nor overall symptom scores were associated with sleep apnea severity. Conclusions: This study demonstrates a very high prevalence of severe sleep apnea in patients with chronic kidney disease. Sleep apnea severity was not associated with quality of life or sleepiness scores and was unrelated to total body water corrected for body size. Routine identification of sleep apnea with polysomnography rather than screening is more appropriate in this group due to the high prevalenceThis study was funded by a grant from The Canberra Hospital Private Practice Fund

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Sleep apnea prevalence in chronic kidney disease - association with total body water and symptoms

Abstract Background Sleep apnea is common and associated with poor outcome in severe chronic kidney disease, but validated screening tools are not available. Our objectives were to determine the prevalence of sleep apnea in this population, to assess the validity of screening for sleep apnea using an ApneaLink device and to investigate the relationship of sleep apnea to; symptoms, spirometry and body water. Methods Patients with glomerular filtration rate ≤30 mL/min/1.73 m2, whether or not they were receiving haemodialysis, were eligible for enrolment. Participants completed symptom questionnaires, performed an ApneaLink recording and had total body water measured using bioimpedance. This was followed by a multi-channel polysomnography recording which is the gold-standard diagnostic test for sleep apnea. Results Fifty-seven participants were enrolled and had baseline data collected, of whom only 2 did not have sleep apnea. An apnea hypopnea index ≥30/h was found in 66% of haemodialysis and 54% of non-dialysis participants. A central apnea index ≥5/h was present in 11 patients, with only one dialysis patient having predominantly central sleep apnea. ApneaLink underestimated sleep apnea severity, particularly in the non-dialysis group. Neither total body water corrected for body size, spirometry, subjective sleepiness nor overall symptom scores were associated with sleep apnea severity. Conclusions This study demonstrates a very high prevalence of severe sleep apnea in patients with chronic kidney disease. Sleep apnea severity was not associated with quality of life or sleepiness scores and was unrelated to total body water corrected for body size. Routine identification of sleep apnea with polysomnography rather than screening is more appropriate in this group due to the high prevalence

Additional file 1: of Sleep apnea prevalence in chronic kidney disease - association with total body water and symptoms

Study sample data. (XLSX 51 kb

Genetic associations with dementia‐related proteinopathy: Application of item response theory

IntroductionAlthough dementia-related proteinopathy has a strong negative impact on public health, and is highly heritable, understanding of the related genetic architecture is incomplete.MethodsWe applied multidimensional generalized partial credit modeling (GPCM) to test genetic associations with dementia-related proteinopathies. Data were analyzed to identify candidate single nucleotide variants for the following proteinopathies: Aβ, tau, α-synuclein, and TDP-43.ResultsFinal included data comprised 966 participants with neuropathologic and WGS data. Three continuous latent outcomes were constructed, corresponding to TDP-43-, Aβ/Tau-, and α-synuclein-related neuropathology endophenotype scores. This approach helped validate known genotype/phenotype associations: for example, TMEM106B and GRN were risk alleles for TDP-43 pathology; and GBA for α-synuclein/Lewy bodies. Novel suggestive proteinopathy-linked alleles were also discovered, including several (SDHAF1, TMEM68, and ARHGEF28) with colocalization analyses and/or high degrees of biologic credibility.DiscussionA novel methodology using GPCM enabled insights into gene candidates for driving misfolded proteinopathies.HighlightsLatent factor scores for proteinopathies were estimated using a generalized partial credit model. The three latent continuous scores corresponded well with proteinopathy severity. Novel genes associated with proteinopathies were identified. Several genes had high degrees of biologic credibility for dementia risk factors