Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia.

BACKGROUND: Supplementation of nicotinamide riboside (NR) ameliorates neuropathology in animal models of ataxia telangiectasia (A-T). In humans, short-term NR supplementation showed benefits in neurological outcome. OBJECTIVES: The study aimed to investigate the safety and benefits of long-term NR supplementation in individuals with A-T. METHODS: A single-arm, open-label clinical trial was performed in individuals with A-T, receiving NR over a period of 2 years. Biomarkers and clinical examinations were used to assess safety parameters. Standardized and validated neuromotor tests were used to monitor changes in neurological symptoms. Using generalized mixed models, test results were compared to expected disease progression based on historical data. RESULTS: NAD+ concentrations increased rapidly in peripheral blood and stabilized at a higher level than baseline. NR supplementation was well tolerated for most participants. The total scores in the neuromotor test panels, as evaluated at the 18-month time point, improved for all but one participant, primarily driven by improvements in coordination subscores and eye movements. A comparison with historical data revealed that the progression of certain neuromotor symptoms was slower than anticipated. CONCLUSIONS: Long-term use of NR appears to be safe and well tolerated, and it improves motor coordination and eye movements in patients with A-T of all ages. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Effect of a physical activity intervention on lower body bone health in childhood cancer survivors: A randomized controlled trial (SURfit).

It remains controversial whether physical activity promotes bone health in childhood cancer survivors (CCS). We aimed to assess the effect of a one-year general exercise intervention on lower body bone parameters of CCS. CCS ≥16 years at enrollment, <16 years at diagnosis and ≥5 years in remission were identified from the national Childhood Cancer Registry. Participants randomized to the intervention group were asked to perform an additional ≥2.5 hours of intense physical activity/week, controls continued exercise as usual. Bone health was assessed as a secondary trial endpoint at baseline and after 12-months. We measured tibia bone mineral density (BMD) and morphology by peripheral quantitative computed tomography and lumbar spine, hip and femoral neck BMD by dual-energy x-ray absorptiometry. We performed intention-to-treat, per protocol, and an explorative subgroup analyses looking at low BMD using multiple linear regressions. One hundred fifty-one survivors (44% females, 7.5 ± 4.9 years at diagnosis, 30.4 ± 8.6 years at baseline) were included. Intention-to-treat analysis revealed no differences in changes between the intervention and control group. Per protocol analyses showed evidence for an improvement in femoral neck and trabecular BMD between 1.5% and 1.8% more in participants being compliant with the exercise program. Trabecular BMD increased 2.8% more in survivors of the intervention group with BMD z-score ≤-1 compared to those starting at z-score >-1. A nonstandardized personalized exercise programs might not be specific enough to promote bone health in CCS, although those compliant and those most in need may benefit. Future trials should include bone stimulating exercise programs targeting risk groups with reduced bone health and motivational features to maximize compliance.

Objectively assessed moderate-to-vigorous physical activity levels among primary school children in Norway: The Health Oriented Pedagogical Project (HOPP).

AIMS: The objective was to investigate moderate-to-vigorous physical activity levels (MVPA) of primary school children at baseline of the Health Oriented Pedagogical Project (HOPP), Norway. METHODS: Data on 2123 children aged 6-12 years were included for analysis (75% participation rate). Average minutes per day in MVPA was objectively measured using accelerometry based on seven-day averages. The sample was analysed for age-, sex-, socioeconomic-, and season-related patterns. A linear regression investigated the moderating effect of these factors as well as body mass index and waist circumference. RESULTS: Some 86.5% of the sample had at least 60 min/day MVPA, averaging 90.7 min/day. The main differences in daily averages were between age groups 6½-9 and 10-12 ( p < .05). Boys (95.8 min/day, 95% CI: 94.1-97.5) were more active than girls (85.6 min/day, 95% CI: 83.9-87.2) in all age groups ( p < .0001). MVPA was lower by 3.5 min ( p < .0001) per additional year of age in the linear regression (R2 = 0.176) and was reduced by 20 min less per day in MVPA in the winter months compared with the summer months ( p < .0001). CONCLUSIONS: Physical activity levels are already in decline from 6-7 years old and are likely to continue to decline into adolescence. Interventions must therefore focus on primary school children.

Cardiovascular risk factors in a child population: The Health Oriented Pedagogical Project (HOPP).

AIMS: The main aim of the present study was to investigate the clustering of risk factors for cardiovascular diseases and metabolic syndrome in a large, healthy representative Norwegian child population. METHODS: From a population of 2817, parents of 2297 children agreed to participate. Values of waist circumference (WC), total cholesterol (TC), high-density lipoprotein (HDL), systolic blood pressure (sysBP), haemoglobin-A1c (HbA1c) and Andersen aerobic fitness test were used to test clustering of cardiometabolic risk factors in this sample. Expected distributions of probability for zero to five risk factors are, respectively, 23.7%, 39.6%, 26.4%, 8.8%, 1.5% and 0.1%. A cardiometabolic risk score from zero to five for each individual was derived by adding the number of variables in the least desirable quartile (highest for WC, sysBP, TC and HbA1c; lowest for aerobic fitness and HDL). RESULTS: A risk ratio of 5.8 (95% confidence interval 0.7-46.9) was found for five risk factors, though the small sample size rendered the results non-significant. An explorative analysis combining children with four and five risk factors did not reveal any significant clustering either. CONCLUSIONS: No clustering of risk factors was found among Norwegian children aged 6-12 years.

Adherence and contamination in a 1-year physical activity program in childhood cancer survivors: A report from the SURfit study.

PURPOSE: Meeting intervention requirements is crucial in behavioral trials. We examined patterns and predictors of physical activity (PA) adherence and contamination in a 1-year individualized randomized controlled PA behavioral intervention in childhood cancer survivors (CCS). METHODS: CCS aged ≥16 at enrolment, <16 at diagnosis, and ≥5 years in remission were identified from the Swiss Childhood Cancer Registry. We asked participants randomized to the intervention group to perform an additional ≥2.5 h of intense PA/week and controls to continue as usual. Adherence to the intervention was assessed by online diary (adherent if ≥2/3 of individual PA goal reached) and contamination for the control group by pre- and post-questionnaire including PA levels (contaminated if >60 min increase/week in PA). Predictors of adherence/contamination including quality of life (36-Item Short Form Survey) were assessed by questionnaire. We used logistic (control group) and mixed logistic regression models (exercise group) to estimate predictors of study adherence and contamination. RESULTS: One hundred and forty-four survivors (30.4 ± 8.7 years old, 43% females) were included. Adherence was 48% (35/73) in the intervention group, while 17% (12/71) of controls contaminated group allocation. Predictors for PA adherence were female sex (OR 2.35, p = 0.03), higher physical (OR 1.34, p = 0.01) and mental quality of life (OR 1.37, p = 0.001), and week into the intervention (OR 0.98, p < 0.001). Clear differences in PA behavior of adherent and non-adherent participants were seen from week four. No significant predictors for contamination were found for controls. CONCLUSION: Adherence to PA behavior interventions remain challenging in both groups. Further long-term trials should consider intense motivational support within the first month, more detailed data collection for the control group, adjustments to power calculations and other study designs to minimize non-adherence and contamination.

The Weather Impact on Physical Activity of 6-12 Year Old Children: A Clustered Study of the Health Oriented Pedagogical Project (HOPP).

It is commonly known that children do not engage in a sufficient amount of physical activity. Weather conditions and day length may influence physical activity of children. Little is known about the relationship between physical activity and seasons. The purpose of this study was to investigate the relationships between weather conditions and physical activity in 6-12 year old children based on hip-worn Actigraph wGT3X-BT accelerometer data. The study sample consisted of 2015 subjects aged 6-12 years from the Health Oriented Pedagogical Project (HOPP) study carried out in Horten municipality and Akershus county, Norway. Six days of sedentary and moderate-to-vigorous physical activity data was gathered in January-June and September-October, 2015, presented as daily averages. The accelerometer-monitored physical activity of children grouped within nine schools was matched with regional weather conditions and assessed with the means of linear mixed models. Increased day length was associated with decreased sedentary behavior. Warmer temperature and dry weather were associated with increased moderate-to-vigorous physical activity after adjusting for age and sex. One-hour increase in daylight resulted in a decrease of sedentary time by, on average, 2 min (95% CI = (-2.577, -0.798)). For every 5 °C increase in temperature (range: -0.95 and 15.51 °C) and dry weather, average moderate-to vigorous physical activity increased by 72 and 67 min (males and females, respectively) (p < 0.001). Days with precipitation had, on average, 10 fewer minutes of moderate-to-vigorous physical activity compared with days without precipitation (95% CI = (-16.704, -3.259)). Higher temperatures and dry weather led to higher physical activity levels, seeing larger increases among boys than girls. A school-based physical activity intervention program should be adjusted regarding local weather conditions in line with the present findings.