| 1. |
- Alsehli, Ahmed M., et al.
(författare)
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Differential associations of statin treatment and polymorphism in genes coding for HMGCR and PCSK9 to risk for insomnia
- 2021
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Ingår i: Frontiers in Bioscience-Landmark. - : Frontiers Media S.A.. - 2768-6701 .- 2768-6698. ; 26:12, s. 1453-1463
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Tidskriftsartikel (refereegranskat)abstract
- Importance: Statins have been linked to an increased risk for insomnia, but the literature is controversial. Moreover, it is unknown, if the potential effects are directly related to the inhibition of the statin target HMGCR, the subsequently lowered cholesterol levels, or other off-target effects of statins. Aims: To investigate the association of statin treatment and genetic proxies of cholesterol lowering drugs with the risk for insomnia and chronotype in a large population-based cohort. Methods: A cross-sectional cohort study based on baseline data collected between 2006–2010 in UK biobank cohort was conducted. European participants without any history of psychiatric/neurological disorders or of stroke and with available genetic data as well as information on statin use were included in the present study. Self-reported measures of insomnia and chronotype were analysed (a) in statin users versus control subjects, (b) subjects carrying single nucleotide polymorphisms (SNPs) in the HMGCR gene, which are associated with reduced enzymatic function and lower cholesterol levels (rs17238484 and rs12916) and (c) subjects carrying a SNP in the PCSK9 gene (rs1159147), which leads to lower cholesterol levels independent of HMGCR. The main analysis were performed using multivariable regression models. Statin treatment and SNPs in HMGCR and PCSK9 genes were used as exposures and main outcomes were insomnia and chronotype. Results: A total of 206,801participants (mean [SD] age, 57.5 [7.9] years; 56% women; 20% statin users) were included in the present study. Statin users had an increased risk of insomnia compared to controls (odds ratio [95% CI], 1.07 [1.03 to 1.11]; p = 1.42 × 10−4). A similar effect was observed for PCSK9 rs11591147-T allele (1.07 [1.01–1.14]; 0.014), while the two gene variants of HMGCR were associated with a reduced risk for insomnia (rs17238484-G: 0.97 [0.95 to 0.99]; 0.014 and rs12916-T: 0.97 [0.96 to 0.99]; 0.002). In regard to chronotype, there was no effect of either statin treatment or HMGCR SNPs, but the PCSK9 rs11591147-T allele was associated with a higher evening preference (1.17 [1.06 to 1.29]; 0.001). Conclusion: Our data suggests that statin treatment can pose an increased risk for insomnia in in the European population. Interestingly, there was no agreement between the effects of statins and the effects of reduced HMGCR activity based on genetic variants, suggesting that the observed unfavourable effect of statins on sleep is conveyed through other targets. This further explains why the literature on statin effects on sleep is not conclusive. Finally our data encourage further investigations into the molecular processes linking statins, HMGCR and PCSK9 to sleep behaviour.
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| 2. |
- Cedernaes, Jonathan, et al.
(författare)
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Acute sleep loss results in tissue-specific alterations in genome-wide DNA methylation state and metabolic fuel utilization in humans
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:8
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Tidskriftsartikel (refereegranskat)abstract
- Curtailed sleep promotes weight gain and loss of lean mass in humans, although the underlying molecular mechanisms are poorly understood. We investigated the genomic and physiological impact of acute sleep loss in peripheral tissues by obtaining adipose tissue and skeletal muscle after one night of sleep loss and after one full night of sleep. We find that acute sleep loss alters genome-wide DNA methylation in adipose tissue, and unbiased transcriptome-, protein-, and metabolite-level analyses also reveal highly tissue-specific changes that are partially reflected by altered metabolite levels in blood. We observe transcriptomic signatures of inflammation in both tissues following acute sleep loss, but changes involving the circadian clock are evident only in skeletal muscle, and we uncover molecular signatures suggestive of muscle breakdown that contrast with an anabolic adipose tissue signature. Our findings provide insight into how disruption of sleep and circadian rhythms may promote weight gain and sarcopenia.
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| 3. |
- Chapman, Colin Daniel, et al.
(författare)
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Experimenter gender and replicability in science
- 2018
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Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 4:1
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Forskningsöversikt (refereegranskat)abstract
- There is a replication crisis spreading through the annals of scientific inquiry. Although some work has been carried out to uncover the roots of this issue, much remains unanswered. With this in mind, this paper investigates how the gender of the experimenter may affect experimental findings. Clinical trials are regularly carried out without any report of the experimenter's gender and with dubious knowledge of its influence. Consequently, significant biases caused by the experimenter's gender may lead researchers to conclude that therapeutics or other interventions are either overtreating or undertreating a variety of conditions. Bearing this in mind, this policy paper emphasizes the importance of reporting and controlling for experimenter gender in future research. As backdrop, it explores what we know about the role of experimenter gender in influencing laboratory results, suggests possible mechanisms, and suggests future areas of inquiry.
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| 4. |
- Chapman, Colin D, et al.
(författare)
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Intranasal insulin in Alzheimer's disease : food for thought
- 2018
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Ingår i: Neuropharmacology. - : Elsevier. - 0028-3908 .- 1873-7064. ; 136, s. 196-201
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Tidskriftsartikel (refereegranskat)abstract
- Accumulating evidence suggests that disrupted brain insulin signaling promotes the development and progression of Alzheimer's disease (AD), driving clinicians to target this circuitry. While both traditional and more modern antidiabetics show promise in combating insulin resistance, intranasal insulin appears to be the most efficient method of boosting brain insulin. Furthermore, intranasal delivery elegantly avoids adverse effects from peripheral insulin administration. However, there remain significant open questions regarding intranasal insulin's efficacy, safety, and potential as an adjunct or mono-therapy. Thus, this review aims to critically evaluate the present evidence and future potential of intranasal insulin as a meaningful treatment for AD.
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| 5. |
- Rångtell, Frida H, et al.
(författare)
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A single night of sleep loss impairs objective but not subjective working memory performance in a sex-dependent manner
- 2019
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Ingår i: Journal of Sleep Research. - : John Wiley & Sons. - 0962-1105 .- 1365-2869. ; 28:1
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Tidskriftsartikel (refereegranskat)abstract
- Acute sleep deprivation can lead to judgement errors and thereby increases the risk of accidents, possibly due to an impaired working memory. However, whether the adverse effects of acute sleep loss on working memory are modulated by auditory distraction in women and men are not known. Additionally, it is unknown whether sleep loss alters the way in which men and women perceive their working memory performance. Thus, 24 young adults (12 women using oral contraceptives at the time of investigation) participated in two experimental conditions: nocturnal sleep (scheduled between 22:30 and 06:30 hours) versus one night of total sleep loss. Participants were administered a digital working memory test in which eight-digit sequences were learned and retrieved in the morning after each condition. Learning of digital sequences was accompanied by either silence or auditory distraction (equal distribution among trials). After sequence retrieval, each trial ended with a question regarding how certain participants were of the correctness of their response, as a self-estimate of working memory performance. We found that sleep loss impaired objective but not self-estimated working memory performance in women. In contrast, both measures remained unaffected by sleep loss in men. Auditory distraction impaired working memory performance, without modulation by sleep loss or sex. Being unaware of cognitive limitations when sleep-deprived, as seen in our study, could lead to undesirable consequences in, for example, an occupational context. Our findings suggest that sleep-deprived young women are at particular risk for overestimating their working memory performance.
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| 6. |
- Tan, Xiao, et al.
(författare)
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Association Between Self-Reported Sleep Duration and Body Composition in Middle-Aged and Older Adults
- 2019
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Ingår i: Journal of Clinical Sleep Medicine (JCSM). - : American Academy of Sleep Medicine (AASM). - 1550-9389 .- 1550-9397. ; 15:3, s. 431-435
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Tidskriftsartikel (refereegranskat)abstract
- STUDY OBJECTIVES: The current study sought to examine whether self-reported sleep duration is linked to an adverse body composition in 19,709 adults aged 45 to 75 years. METHODS: All variables used in the current study were derived from the Swedish EpiHealth cohort study. Habitual sleep duration was measured by questionnaires. Body composition was assessed by bioimpedance. The main outcome variables were fat mass and fat-free mass (in kg). Analysis of covariance adjusting for age, sex, fat mass in the case of fat-free mass (and vice versa), leisure time physical activity, smoking, and alcohol consumption was used to investigate the association between sleep duration and body composition. RESULTS: Short sleep (defined as ≤ 5 hours sleep per day) and long sleep (defined as 8 or more hours of sleep per day) were associated with lower fat-free mass and higher fat mass, compared with 6 to 7 hours of sleep duration (P < .05). CONCLUSIONS: These observations could suggest that both habitual short and long sleep may contribute to two common clinical phenotypes in middle-aged and older humans, ie, body adiposity and sarcopenia. However, the observational nature of our study does not allow for causal interpretation.
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| 7. |
- Tan, Xiao, et al.
(författare)
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Associations between chronotype, MTNR1B genotype and risk of type 2 diabetes in UK Biobank
- 2020
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 287:2, s. 189-196
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo examine the association between the MTNR1B G risk allele, type 2 diabetes (T2D) and chronotype in the UK Biobank.MethodsData from the baseline investigation of the UK Biobank were utilized (n = 337 083 White British; mean age: 56.9 years; 54% women). MTNR1B rs10830963 was directly genotyped [CC (reference group), CG and GG]. Chronotype was divided into four categories: definitely morning (reference group); more morning than evening; more evening than morning; and definitely evening. Logistic regression analyses were performed to estimate odds ratios and 95% confidence intervals (CIs) for T2D, controlling for age, sex and other confounders.ResultsCarriers of the rs10830963 risk allele had a higher risk of T2D [CG vs. CC: OR (95% CI) 1.10 (1.07, 1.15); GG vs. CC: 1.21 (1.14, 1.29)]. Compared with definitely morning chronotype, participants with definitely evening chronotype exhibited the highest risk of T2D [1.25 (1.17, 1.33)]. Despite a nonsignificant interaction between chronotype and the risk allele [0.98 (0.94, 1.01), P = 0.176 for interaction term], we found that definitely evening chronotype (vs. definitely morning) was linked with a higher risk of T2D amongst CC and CG but not GG carriers. Additionally, we saw that the GG genotype (vs. CC) was associated with a higher risk of T2D across all chronotype categories, except for definitely evening.ConclusionOur findings suggest that the MTNR1B G risk allele and late chronotype increase the risk of T2D. The association between late chronotype and higher risk of T2D appears to vary across MTNR1B rs10830963 genotypes.
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| 8. |
- Tan, Xiao, et al.
(författare)
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Self-reported sleep disturbances and prostate cancer morbidity and mortality in Swedish men : A longitudinal study over 40 years
- 2018
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Ingår i: Journal of Sleep Research. - : Wiley. - 0962-1105 .- 1365-2869. ; 27:6
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Tidskriftsartikel (refereegranskat)abstract
- The present study, with an observational period of about 40 years, examined the association between self-reported sleep disturbances (i.e. problems with falling and staying asleep; use of hypnotics) and prostate cancer morbidity and mortality in initially 2322 men (all 50 years old at baseline). Self-reported sleep disturbances and established risk factors (e.g. age, lower urinary tract symptoms, smoking and family history of cancer) were measured at ages 50 and 70 years. Information about prostate cancer diagnosis and deaths as a result of prostate cancer was available from the National Cancer Registry and the Swedish Civil Registry of Morbidity. During the observational period, 263 participants developed prostate cancer (11% of the total cohort); 146 of them died as a result of prostate cancer. There was no association between sleep disturbances and prostate cancer morbidity or mortality (hazard ratio 1.09, 95% confidence interval (CI) 0.79, 1.52, and hazard ratio 1.21, 95% CI 0.77, 1.91, respectively). Similar findings were observed when examining associations between single sleep disturbance parameters and prostate cancer morbidity and mortality. Our study does not provide evidence that reports of sleep disturbances increase the risk of prostate cancer morbidity or mortality in middle to older-aged men. Therefore, assessing subjective sleep problems may not meaningfully help to identify men at risk of developing prostate cancer or dying of this devastating condition.
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| 9. |
- Titova, Olga E, et al.
(författare)
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Association between shift work history and performance on the trail making test in middle-aged and elderly humans : The EpiHealth study
- 2016
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580 .- 1558-1497. ; 45, s. 23-29
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Tidskriftsartikel (refereegranskat)abstract
- Shift work has been proposed to promote cognitive disturbances in humans; however, conflicting evidence is also present. By using data from 7143 middle-aged and elderly humans (45-75 years) who participated in the Swedish EpiHealth cohort study, the present analysis sought to investigate whether self-reported shift work history would be associated with performance on the trail making test (TMT). The TMT has been proposed to be a useful neuropsychological tool to evaluate humans' executive cognitive function, which is known to decrease with age. After adjustment for potential confounders (e.g., age, education, and sleep duration), it was observed that current and recent former shift workers (worked shifts during the past 5 years) performed worse on the TMT than nonshift workers. In contrast, performance on the TMT did not differ between past shift workers (off from shift work for more than 5 years) and nonshift workers. Collectively, our results indicate that shift work history is linked to poorer performance on the TMT in a cohort of middle-aged and elderly humans.
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| 10. |
- Titova, Olga E, et al.
(författare)
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Association between sleep duration and executive function differs between diabetic and non-diabetic middle-aged and older adults
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 111
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Tidskriftsartikel (refereegranskat)abstract
- Executive function is defined as a set of cognitive skills that are necessary to plan, monitor, and execute a sequence of goal-directed complex actions. Executive function is influenced by a variety of factors, including habitual sleep duration and diabetes. In the present study, we investigated in 18,769 Swedish adults (mean age: 61 y) the association between executive function, diabetes, and self-reported sleep duration. We observed a significant interaction between diabetes and sleep duration for the Trail Making Test (TMT) ratio (P < 0.01). This ratio is a measure of executive function where higher values indicate worse performance. Among diabetic participants (n = 1,523), long (defined as ≥9 h per day) vs. normal sleep duration (defined as 7–8 hours per day) was associated with a higher TMT ratio (P < 0.05). Similar significant results were observed in diabetic individuals without pharmacological treatment for diabetes (n = 1,062). Among non-diabetic participants (n = 17,246), no association between long sleep duration and the TMT ratio was observed (P > 0.05). Instead, short (defined as <7 h per day) vs. normal sleep duration was linked to a higher TMT ratio (P < 0.05). These findings suggest that the association between sleep duration and executive function differs between diabetic and non-diabetic middle-aged and older adults. Based on the cross-sectional design of the study, no firm conclusions can be drawn on the causality of the relations.
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