Effects of low- and high-intensity physical exercise on physical and cognitive function in older persons with dementia:A randomized controlled trial

Background: Potential moderators such as exercise intensity or apolipoprotein-E4 (ApoE4) carriership may determine the magnitude of exercise effects on physical and cognitive functions in patients with dementia (PwD). We determined the effects of a 24-week aerobic and strength training program with a low- and high-intensity phase on physical and cognitive function. Methods: In an assessor-blinded randomized trial, 91 PwD (all-cause dementia, recruited from daycare and residential care facilities, age 82.3 ± 7.0 years, 59 women, Mini-Mental State Examination 20.2 ± 4.4) were allocated to the exercise or control group. In the exercise group, PwD participated in a walking and lower limb strength training program with 12 weeks low- and 12 weeks high-intensity training offered three times/week. Attention-matched control participants performed flexibility exercises and recreational activities. We assessed adherence, compliance, and exercise intensity for each session. We assessed physical (endurance, gait speed, mobility, balance, leg strength) and cognitive (verbal memory, visual memory, executive function, inhibitory control, psychomotor speed) functions with performance-based tests at baseline and after 6, 12, 18, 24, and 36 weeks (follow-up). ApoE4 carriership was determined post-intervention. Results: Sixty-nine PwD were analyzed. Their mean attendance was ~ 60% during the study period. There were no significant effects of the exercise vs. control intervention on endurance, mobility, balance, and leg strength in favor of the exercise group (Cohen's d = 0.13-0.18). Gait speed significantly improved with ~ 0.05 m/s after the high-intensity phase for exercise participants (Cohen's d = 0.41) but declined at follow-up. There were no significant effects of the exercise vs. control intervention on any of the cognitive measures (Cohen's d ~ - 0.04). ApoE4 carriership did not significantly moderate exercise effects on physical or cognitive function. Conclusions: Exercise was superior to control activities for gait speed in our sample of PwD. However, the training effect provided no protection for mobility loss after detraining (follow-up). There were no beneficial effects of the exercise vs. control group on cognitive function. Exercise intensity moderated the effects of exercise on gait speed. ApoE4 carriership moderated the effect of exercise on global cognition only (trend level). Trial registration: Netherlands Trial Register, NTR5035. Registered on 2 March 2015

The effect of an interactive cycling training on cognitive functioning in older adults with mild dementia: study protocol for a randomized controlled trial

Contains fulltext : 168861.pdf (publisher's version ) (Open Access)Background: To date there is no cure or an effective disease-modifying drug to treat dementia. Available acetylcholine-esterase inhibiting drugs or memantine only produce small benefits on cognitive and behavioural functioning and their clinical relevance remains controversial. Combined cognitive-aerobic interventions are an appealing alternative or add-on to current pharmacological treatments. The primary aim of this study is to investigate the efficacy of a combined cognitive-aerobic training and a single aerobic training compared to an active control group in older adults with mild dementia. We expect to find a beneficial effect on executive functioning in both training regimes, compared to the control intervention, with the largest effect in the combined cognitive-aerobic group. Secondary, intervention effects on cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty and quality of life are studied. Methods: The design is a single-blind, randomized controlled trial (RCT) with three groups: a combined cognitive-aerobic bicycle training (interactive cycling), a single aerobic bicycle training and a control intervention, which consists of stretching and toning exercises. Older adults with mild dementia follow a 12-week training program consisting of three training sessions of 30-40 min per week. The primary study outcome is objective executive functioning measured with a neuropsychological assessment. Secondary measures are objective cognitive functioning in other domains, physical functioning, physical activity levels, activities of daily living, frailty, mood and quality of life. The three groups are compared at baseline, after 6 and 12 weeks of training, and at 24-week follow-up. Discussion: This study will provide novel information on the effects of an interactive cycling training on executive function in older adults with mild dementia. Furthermore, since this study has both a combined cognitive-aerobic training and a single aerobic training group the effectiveness of the different components of the intervention can be identified. The results of this study may be used for physical and mental activity recommendations in older adults with dementia.8 p

Grain Surface Models and Data for Astrochemistry

AbstractThe cross-disciplinary field of astrochemistry exists to understand the formation, destruction, and survival of molecules in astrophysical environments. Molecules in space are synthesized via a large variety of gas-phase reactions, and reactions on dust-grain surfaces, where the surface acts as a catalyst. A broad consensus has been reached in the astrochemistry community on how to suitably treat gas-phase processes in models, and also on how to present the necessary reaction data in databases; however, no such consensus has yet been reached for grain-surface processes. A team of ∼25 experts covering observational, laboratory and theoretical (astro)chemistry met in summer of 2014 at the Lorentz Center in Leiden with the aim to provide solutions for this problem and to review the current state-of-the-art of grain surface models, both in terms of technical implementation into models as well as the most up-to-date information available from experiments and chemical computations. This review builds on the results of this workshop and gives an outlook for future directions

Reduced Vitamin K Status as a Potentially Modifiable Risk Factor of Severe Coronavirus Disease 2019

BACKGROUND: Respiratory failure and thromboembolism are frequent in SARS-CoV-2-infected patients. Vitamin K activates both hepatic coagulation factors and extrahepatic endothelial anticoagulant protein S, required for thrombosis prevention. In times of vitamin K insufficiency, hepatic procoagulant factors are preferentially activated over extrahepatic proteins. Vitamin K also activates matrix Gla protein (MGP), which protects against pulmonary and vascular elastic fiber damage. We hypothesized that vitamin K may be implicated in coronavirus disease 2019 (COVID-19), linking pulmonary and thromboembolic disease. METHODS: 135 hospitalized COVID-19 patients were compared with 184 historical controls. Poor outcome was defined as invasive ventilation and/or death. Inactive vitamin K-dependent MGP (dp-ucMGP) and prothrombin (PIVKA-II) were measured, inversely related to extrahepatic and hepatic vitamin K status, respectively. Desmosine was measured to quantify the rate of elastic fiber degradation. Arterial calcification severity was assessed by computed tomography. RESULTS: Dp-ucMGP was elevated in COVID-19 patients compared to controls (p<0.001), with even higher dp-ucMGP in patients with poor outcomes (p<0.001). PIVKA-II was normal in 82.1% of patients. Dp-ucMGP was correlated with desmosine (p<0.001), and coronary artery (p=0.002) and thoracic aortic (p<0.001) calcification scores. CONCLUSIONS: Dp-ucMGP was severely increased in COVID-19 patients, indicating extrahepatic vitamin K insufficiency, which was related to poor outcome while hepatic procoagulant factor II remained unaffected. These data suggest a mechanism of pneumonia-induced extrahepatic vitamin K depletion leading to accelerated elastic fiber damage and thrombosis in severe COVID-19 due to impaired activation of MGP and endothelial protein S, respectively. A clinical trial could assess whether vitamin K administration improves COVID-19 outcomes

Correlating locations in ipsilateral breast tomosynthesis views using an analytical hemispherical compression model

Item does not contain fulltextTo improve cancer detection in mammography, breast examinations usually consist of two views per breast. In order to combine information from both views, corresponding regions in the views need to be matched. In 3D digital breast tomosynthesis (DBT), this may be a difficult and time-consuming task for radiologists, because many slices have to be inspected individually. For multiview computer-aided detection (CAD) systems, matching corresponding regions is an essential step that needs to be automated. In this study, we developed an automatic method to quickly estimate corresponding locations in ipsilateral tomosynthesis views by applying a spatial transformation. First we match a model of a compressed breast to the tomosynthesis view containing a point of interest. Then we estimate the location of the corresponding point in the ipsilateral view by assuming that this model was decompressed, rotated and compressed again. In this study, we use a relatively simple, elastically deformable sphere model to obtain an analytical solution for the transformation in a given DBT case. We investigate three different methods to match the compression model to the data by using automatic segmentation of the pectoral muscle, breast tissue and nipple. For validation, we annotated 208 landmarks in both views of a total of 146 imaged breasts of 109 different patients and applied our method to each location. The best results are obtained by using the centre of gravity of the breast to define the central axis of the model, around which the breast is assumed to rotate between views. Results show a median 3D distance between the actual location and the estimated location of 14.6 mm, a good starting point for a registration method or a feature-based local search method to link suspicious regions in a multiview CAD system. Approximately half of the estimated locations are at most one slice away from the actual location, which makes the method useful as a mammographic workstation tool for radiologists to interactively find corresponding locations in ipsilateral tomosynthesis views

MRI versus mammography for breast cancer screening in women with familial risk (FaMRIsc):a multicentre, randomised, controlled trial

Background Approximately 15% of all breast cancers occur in women with a family history of breast cancer, but for whom no causative hereditary gene mutation has been found. Screening guidelines for women with familial risk of breast cancer differ between countries. We did a randomised controlled trial (FaMRIsc) to compare MRI screening with mammography in women with familial risk. Methods In this multicentre, randomised, controlled trial done in 12 hospitals in the Netherlands, women were eligible to participate if they were aged 30-55 years and had a cumulative lifetime breast cancer risk of at least 20% because of a familial predisposition, but were BRCA1, BRCA2, and TP53 wild-type. Participants who were breast-feeding, pregnant, had a previous breast cancer screen, or had a previous a diagnosis of ductal carcinoma in situ were eligible, but those with a previously diagnosed invasive carcinoma were excluded. Participants were randomly allocated (1:1) to receive either annual MRI and clinical breast examination plus biennial mammography (MRI group) or annual mammography and clinical breast examination (mammography group). Randomisation was done via a web-based system and stratified by centre. Women who did not provide consent for randomisation could give consent for registration if they followed either the mammography group protocol or the MRI group protocol in a joint decision with their physician. Results from the registration group were only used in the analyses stratified by breast density. Primary outcomes were number, size, and nodal status of detected breast cancers. Analyses were done by intention to treat. This trial is registered with the Netherlands Trial Register, number NL2661. Findings Between Jan 1, 2011, and Dec 31, 2017, 1355 women provided consent for randomisation and 231 for registration. 675 of 1355 women were randomly allocated to the MRI group and 680 to the mammography group. 218 of 231 women opting to be in a registration group were in the mammography registration group and 13 were in the MRI registration group. The mean number of screening rounds per woman was 4.3 (SD 1.76). More breast cancers were detected in the MRI group than in the mammography group (40 vs 15; p=0.0017). Invasive cancers (24 in the MRI group and eight in the mammography group) were smaller in the MRI group than in the mammography group (median size 9 mm [5-14] vs 17 mm [13-22]; p=0.010) and less frequently node positive (four [17%] of 24 vs five [63%] of eight; p=0.023). Tumour stages of the cancers detected at incident rounds were significantly earlier in the MRI group (12 [48%] of 25 in the MRI group vs one [7%] of 15 in the mammography group were stage T1a and T1b cancers; one (4%) of 25 in the MRI group and two (13%) of 15 in the mammography group were stage T2 or higher; p=0.035) and node-positive tumours were less frequent (two [11%] of 18 in the MRI group vs five [63%] of eight in the mammography group; p=0.014). All seven tumours stage T2 or higher were in the two highest breast density categories (breast imaging reporting and data system categories C and D; p=0.0077) One patient died from breast cancer during follow-up (mammography registration group). Interpretation MRI screening detected cancers at an earlier stage than mammography. The lower number of late-stage cancers identified in incident rounds might reduce the use of adjuvant chemotherapy and decrease breast cancer-related mortality. However, the advantages of the MRI screening approach might be at the cost of more false-positive results, especially at high breast density. Copyright (C) 2019 Elsevier Ltd. All rights reserved