Effect of moderate to high intensity aerobic exercise on blood pressure in young adults : the TEPHRA open, two-arm, parallel superiority randomized clinical trial

Background Exercise is advised for young adults with elevated blood pressure, but no trials have investigated efficacy at this age. We aimed to determine whether aerobic exercise, self-monitoring and motivational coaching lowers blood pressure in this group. Methods The study was a single-centre, open, two-arm, parallel superiority randomized clinical trial with open community-based recruitment of physically-inactive 18–35 year old adults with awake 24 h blood pressure 115/75mmHg-159/99 mmHg and BMI37 weeks) to the intervention group, who received 16-weeks aerobic exercise training (three aerobic training sessions per week of 60 min per session at 60–80% peak heart rate, physical activity self-monitoring with encouragement to do 10,000 steps per day and motivational coaching to maintain physical activity upon completion of the intervention. The control group were sign-posted to educational materials on hypertension and recommended lifestyle behaviours. Investigators performing statistical analyses were blinded to group allocation. The primary outcome was 24 h awake ambulatory blood pressure (systolic and diastolic) change from baseline to 16-weeks on an intention-to-treat basis. Clinicaltrials.gov registered on March 30, 2016 (NCT02723552). Findings Enrolment occurred between 30/06/2016-26/10/2018. Amongst the 203 randomized young adults (n = 102 in the intervention group; n = 101 in the control group), 178 (88%; n = 76 intervention group, n = 84 control group) completed 16-week follow-up and 160 (79%; n = 68 intervention group, n = 69 control group) completed 52-weeks follow-up. There were no group differences in awake systolic (0·0 mmHg [95%CI, -2·9 to 2·8]; P = 0·98) or awake diastolic ambulatory blood pressure (0·6 mmHg [95%CI, -1·4. to 2·6]; P = 0·58). Aerobic training increased peak oxygen uptake (2·8 ml/kg/min [95%CI, 1·6 to 4·0]) and peak wattage (14·2watts [95%CI, 7·6 to 20·9]) at 16-weeks. There were no intervention effects at 52-weeks follow-up. Intepretation These results do not support the exclusive use of moderate to high intensity aerobic exercise training for blood pressure control in young adults. Funding Wellcome Trust, British Heart Foundation, National Institute for Health Research, Oxford Biomedical Research Centre

Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men:a randomized clinical trial

\u3cp\u3eIMPORTANCE: Increasing evidence suggests a relationship between poor sleep and the risk of developing Alzheimer disease. A previous study found an effect of sleep on β-amyloid (Aβ), which is a key protein in Alzheimer disease pathology.\u3c/p\u3e\u3cp\u3eOBJECTIVE: To determine the effect of 1 night of total sleep deprivation on cerebrospinal fluid Aβ42 protein levels in healthy middle-aged men.\u3c/p\u3e\u3cp\u3eDESIGN, SETTING, AND PARTICIPANTS: The Alzheimer, Wakefulness, and Amyloid Kinetics (AWAKE) study at the Radboud Alzheimer Center, a randomized clinical trial that took place between June 1, 2012, and October 1, 2012. Participants were cognitively normal middle-aged men (40-60 years of age) with normal sleep (n = 26) recruited from the local population.\u3c/p\u3e\u3cp\u3eINTERVENTIONS: Participants were randomized to 1 night with unrestricted sleep (n = 13) or 1 night of total sleep deprivation (24 hours of wakefulness) (n = 13).\u3c/p\u3e\u3cp\u3eMAIN OUTCOMES AND MEASURES: Sleep was monitored using continuous polysomnographic recording from 3 pm until 10 am. Cerebrospinal fluid samples were collected using an intrathecal catheter at defined times to compare cerebral Aβ42 concentrations between evening and morning.\u3c/p\u3e\u3cp\u3eRESULTS: A night of unrestricted sleep led to a 6% decrease in Aβ42 levels of 25.3 pg/mL (95% CI [0.94, 49.6], P = .04), whereas sleep deprivation counteracted this decrease. When accounting for the individual trajectories of Aβ42 over time, a difference of 75.8 pg/mL of Aβ42 was shown between the unrestricted sleep and sleep deprivation group (95% CI [3.4, 148.4], P = .04). The individual trajectories of evening and morning Aβ42 concentrations differed between the unrestricted sleep and sleep deprivation groups (P = .04) in contrast to stable Aβ40, tau, and total protein levels.\u3c/p\u3e\u3cp\u3eCONCLUSIONS AND RELEVANCE: Sleep deprivation, or prolonged wakefulness, interferes with a physiological morning decrease in Aβ42. We hypothesize that chronic sleep deprivation increases cerebral Aβ42 levels, which elevates the risk of Alzheimer disease.\u3c/p\u3e\u3cp\u3eTRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01194713.\u3c/p\u3

Sleep-cognition hypothesis in maritime pilots, what is the effect of long-term work-related poor sleep on cognition and amyloid accumulation in healthy middle-aged maritime pilots:methodology of a case-control study

\u3cp\u3eINTRODUCTION: Evidence indicates a bidirectional relationship between poor sleep and Alzheimer's disease (AD). While AD may lead to disruption of normal sleep, poor sleep in itself may play a causal role in the development of AD by influencing the production and/or clearance of the amyloid-beta (Aβ) protein. This led to the hypothesis that extended periods (>10 years) of sleep loss could lead to Aβ accumulation with subsequent cognitive AD-related decline. This manuscript describes the methodology of the SCHIP study, a cohort study in maritime pilots that aims at investigating the relationship between prolonged work-related sleep loss, cognitive function and amyloid accumulation among healthy middle-aged maritime pilots, to test the hypothesis that prolonged sleep loss increases the risk of AD-related cognitive decline.\u3c/p\u3e\u3cp\u3eMETHODS: Our study sample consists of a group of healthy middle-aged maritime pilots (n=20), who have been exposed to highly irregular work schedules for more than 15 years. The maritime pilots will be compared to a group of healthy, age and education-matched controls (n=20) with normal sleep. Participants will complete 10 days of actigraphy (Actiwatch 2, Philips Respironics) combined with a sleep-wake diary. They will undergo one night of polysomnography, followed by comprehensive assessment of cognitive function. Additionally, participants will undergo amyloid positron emission tomography-CT to measure brain amyloid accumulation and MRI to investigate atrophy and vascular changes.\u3c/p\u3e\u3cp\u3eANALYSIS: All analyses will be performed using IBM SPSS V.20.0 (SPSS). We will perform independent samples t-tests to compare all outcome parameters.\u3c/p\u3e\u3cp\u3eETHICS AND DISSEMINATION: The study protocol was approved by our institutional ethical review board (NL55712.091.16, file number 2016-2337) and will be performed according to Good Clinical Practice rules. Data and results will be published in 2020.\u3c/p\u3

Effects of long-term sleep disruption on cognitive function and brain amyloid-β burden: a case-control study

BACKGROUND: Recent evidence indicates that disrupted sleep could contribute to the development of Alzheimer's disease by influencing the production and/or clearance of the amyloid-β protein. We set up a case-control study to investigate the association between long-term work-induced sleep disruption, cognitive function, and brain amyloid-β burden. METHODS: Nineteen male maritime pilots (aged 48-60 years) with chronic work-related sleep disruption and a sex-, age-, and education-matched control sample (n = 16, aged 50-60 years) with normal sleep completed the study. Primary sleep disorders were ruled out with in-lab polysomnography. Additional sleep measurements were obtained at home using actigraphy, sleep-wake logs, and a single-lead EEG device. Cognitive function was assessed with a neuropsychological test battery, sensitive to early symptomatic Alzheimer's disease. Brain amyloid-β burden was assessed in maritime pilots using 18F-flutemetamol amyloid PET-CT. RESULTS: Maritime pilots reported significantly worse sleep quality (Pittsburgh Sleep Quality Index (PSQI) = 8.8 ± 2.9) during work weeks, compared to controls (PSQI = 3.2 ± 1.4; 95% CI 0.01 to 2.57; p = 0.049). This was confirmed with actigraphy-based sleep efficiency (86% ± 3.8 vs. 89.3% ± 4.3; 95% CI 0.43 to 6.03; p = 0.03). Home-EEG recordings showed less total sleep time (TST) and deep sleep time (DST) during work weeks compared to rest weeks (TST 318.56 (250.21-352.93) vs. TST 406.17 (340-425.98); p = 0.001; DST 36.75 (32.30-58.58) vs. DST 51.34 (48.37-69.30); p = 0.005)). There were no differences in any of the cognitive domains between the groups. For brain amyloid-β levels, mean global cortical standard uptake value ratios of 18F-flutemetamol were all in the normal range (1.009 ± 0.059; 95% CI 0.980 to 1.037), confirmed by visual reads. CONCLUSIONS: Capitalizing on the particular work-rest schedule of maritime pilots, this study with a small sample size observed that long-term intermittent sleep disruption had no effects on global brain amyloid-β levels or cognitive function

Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML

Open access courtsey of Blood Journa

The role of the dopamine D1 receptor in social cognition : Studies using a novel genetic rat model

Social cognitionisan endophenotype that is impaired in schizophrenia and several other (comorbid) psychiatric disorders. One of the modulators of social cognition is dopamine, but its role is not clear. The effects of dopamine are mediated through dopamine receptors, including the dopamine D1 receptor (Drd1). Because current Drd1 receptor agonists are not Drd1 selective, pharmacological tools are not sufficient to delineate the role of the Drd1. Here, we describe a novel rat model with a genetic mutation in Drd1 in which we measured basic behavioural phenotypes and social cognition. The I116S mutation was predicted to render the receptor less stable. In line with this computational prediction, this Drd1 mutation led to a decreased transmembrane insertion of Drd1, whereas Drd1 expression, as measured by Drd1 mRNA levels, remained unaffected. Owing to decreased transmembrane Drd1 insertion, the mutant rats displayed normal basic motoric and neurological parameters, as well as locomotor activity and anxiety-like behaviour. However, measures of social cognition like social interaction, scent marking, pup ultrasonic vocalizations and sociability, were strongly reduced in the mutant rats. This profile of the Drd1 mutant rat offers the field of neuroscience a novel genetic rat model to study a series of psychiatric disorders including schizophrenia, autism, depression, bipolar disorder and drug addiction