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- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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2. |
- Hallgren, Mats, et al.
(författare)
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Habitual physical activity levels predict treatment outcomes in depressed adults : A prospective cohort study.
- 2016
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Ingår i: Preventive Medicine. - : Elsevier BV. - 0091-7435 .- 1096-0260. ; 88, s. 53-58
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Exercise is an efficacious stand-alone therapy for mild-to-moderate depression, but little is known about the influence of physical activity levels on responses to depression treatment. This study aimed to prospectively assess the association between self-reported habitual physical activity levels and depression severity following a 12-week intervention.METHOD: 629 adults (75% women; aged 18-71years) with mild-to-moderate depression were recruited from primary care centres across Sweden and treated for 12weeks. The interventions included internet-based cognitive behavioural therapy (ICBT) and 'usual care' (CBT or supportive counselling). One third of all participants were taking anti-depressant medication. The primary outcome was the change in depression severity assessed using the Montgomery-Åsberg Depression Rating Scale (MADRS). Habitual physical activity levels were self-rated and based on the estimated frequency, duration and intensity of total physical activity, including planned exercise, 'during a typical week'. Prospective associations were explored using linear regression models (percentage change) with 95% confidence intervals (CI's).RESULTS: Following adjustment for relevant covariates, high levels of habitual physical activity were associated with larger relative reductions in depression severity compared to low physical activity (β=-9.19, 95% CI=-18.46, -0.09, p=0.052) and moderate physical activity (β=-10.81, 95% CI=-21.09, -0.53, p<0.05), respectively.CONCLUSION: Adults who routinely engage in high levels of physical activity respond more favourably to CBT-focused depression treatments than adults who engage in low-to-moderate levels of activity. The optimal level of physical activity associated with reductions in depression severity corresponds to consensus recommendations for maximizing general health. One limitation is the use of self-reported physical activity data.
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3. |
- Helgadóttir, Björg, et al.
(författare)
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Changes in physical activity and sedentary behavior associated with an exercise intervention in depressed adults
- 2017
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Ingår i: Psychology of Sport And Exercise. - : Elsevier BV. - 1469-0292 .- 1878-5476. ; 30, s. 10-18
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Tidskriftsartikel (refereegranskat)abstract
- Background Exercise is beneficial for depression, but less is known about its impact on post-intervention physical activity and sedentary behavior. The aim of this paper was to determine the extent to which participation in light-, moderate- and vigorous-intensity exercise intervention influenced habitual physical activity and sedentary behavior patterns in depressed adults. Methods Accelerometer data was collected pre- and post-intervention from depressed participants randomized to one of three 12-week intervention groups: light (n = 21), moderate (n = 25) and vigorous (n = 22) exercise. Mixed models examined changes in time spent sedentary and in light and moderate-to-vigorous physical activity (MVPA); time accumulated in sedentary and MVPA bouts; and, number of MVPA bouts and interruptions in sedentary time. Results Overall sedentary time decreased while light activity time increased across all intervention groups but not significantly so. The light exercise intervention group reduced MVPA minutes (−8.22, 95% CI: −16.44, −0.01), time in MVPA bouts (−8.44, 95% CI: −14.27, −2.62), and number of activity bouts (−0.43, 95% CI: −0.77, −0.09). The moderate exercise intervention group reduced time in MVPA bouts (−6.27, 95% CI: −11.71, −0.82) and number of sedentary interruptions (−6.07, 95% CI: −9.30, −2.84). No changes were observed for the vigorous exercise intervention group. Conclusions The exercise intervention led to an increase in overall light physical activity and decrease in sedentary time, though neither change was statistically significant. Participation in the light and moderate exercise intervention groups was associated with reductions of time in MVPA bouts, but this was not evident for the vigorous exercise intervention group.
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4. |
- Howard, Bethany J., et al.
(författare)
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Self-Reported Sitting Time, Physical Activity and Fibrinolytic and Other Novel Cardio-Metabolic Biomarkers in Active Swedish Seniors
- 2016
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Ingår i: PLOS ONE. - San Francisco, USA : Public Library od Scence. - 1932-6203. ; 11:9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Too much sitting is linked with an increased risk of cardiovascular disease and mortality. The mediating mechanisms for these associations are largely unknown, however dysregulated fibrinolysis have emerged as a possible contributor.Objective: We examined the associations of self-reported overall sitting time and physical activity with fibrinolytic and other novel cardio-metabolic biomarkers in older adults.Materials and Methods: Data was analysed for 364 participants (74±7 yrs) of the Active Seniors group (retired, living independently in their own homes). Linear regression analyses examined associations of categories of categories of sitting time (≤3, 3-6, >6 hrs/day) and overall physical activity (Low, Moderate and High) with biomarkers in serum or plasma, adjusting for age, gender and smoking (with further adjustment for either overall physical activity or sitting time and BMI in secondary analyses).Results: Compared to sitting ≤ 3 hrs/day, sitting >6 hrs/day was associated with higher tissue plasminogen activator (tPA) and tissue plasminogen activator/plasminogen activator inhibitor-1 complex (tPA-PAI-1 complex). These associations were not independent of overall physical activity or BMI. Compared to those in the high physical activity, low physical activity was associated with a higher BMI, high-sensitivity C-reactive protein (hs-CRP) and tPA-PAI-1 complex levels. Only the associations of BMI and hs-CRP were independent of sitting time.Conclusions: These findings provide preliminary cross-sectional evidence for the relationships of sitting time with fibrinolytic markers in older adults. They also reinforce the importance of regular physical activity for cardio-metabolic health.
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- Wennberg, Patrik, et al.
(författare)
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Acute effects of breaking up prolonged sitting on fatigue and cognition : a pilot study
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6:2
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: To compare the acute effects of uninterrupted sitting with sitting interrupted by brief bouts of light-intensity walking on self-reported fatigue, cognition, neuroendocrine biomarkers and cardiometabolic risk markers in overweight/obese adults.Design: Randomised two-condition crossover trial.Setting: Laboratory study conducted in Melbourne, Australia.Participants: 19 overweight/obese adults (45–75 years).Interventions: After an initial 2 h period seated, participants consumed a meal-replacement beverage and completed (on 2 days separated by a 6-day washout period) each condition over the next 5 h: uninterrupted sitting (sedentary condition) or sitting with 3 min bouts of light-intensity walking every 30 min (active condition).Primary outcome measures: Self-reported fatigue, executive function and episodic memory at 0 h, 4 h and 7 h.Secondary outcome measures: Neuroendocrine biomarkers and cardiometabolic risk markers (blood collections at 0 h, 4 h and 7 h, blood pressure and heart rate measured hourly and interstitial glucose measured using a continuous glucose monitoring system).Results: During the active condition, fatigue levels were lower at 4 h (−13.32 (95% CI −23.48 to −3.16)) and at 7 h (−10.73 (95% CI −20.89 to −0.58)) compared to the sedentary condition. Heart rate was higher at 4 h (4.47 (95% CI 8.37 to 0.58)) and at 7 h (4.32 (95% CI 8.21 to 0.42)) during the active condition compared to the sedentary condition. There were no significant differences between conditions by time for other variables. In the sedentary condition, changes in fatigue scores over time correlated with a decrease in heart rate and plasma dihydroxyphenylalanine (DOPA) and an increase in plasma dihydroxyphenylglycol (DHPG).Conclusions: Interrupting prolonged sitting with light-intensity walking breaks may be an effective fatigue countermeasure acutely. Fatigue levels corresponded with the heart rate and neuroendocrine biomarker changes in uninterrupted sitting in this pilot study. Further research is needed to identify potential implications, particularly for the occupational health context.
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6. |
- Wheeler, Michael J., et al.
(författare)
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Morning exercise mitigates the impact of prolonged sitting on cerebral blood flow in older adults
- 2019
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Ingår i: Journal of applied physiology. - Rockville : American Physiological Society. - 8750-7587 .- 1522-1601. ; 126:4, s. 1049-1055
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Tidskriftsartikel (refereegranskat)abstract
- Preventing declines in cerebral blood flow is important for maintaining optimal brain health with aging. We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cerebral blood velocity over 8 h in older adults. In a randomized crossover trial, overweight/obese older adults (n = 12, 70 +/- 7 yr; 30.4 +/- 4.3 kg/m2), completed three acute conditions (6-day washout); SIT: prolonged sitting (8 h, control); EX + SIT: sitting (1 h), moderate-intensity walking (30 min), followed by uninterrupted sitting (6.5 h); and EX + BR: sitting (1 h), moderate-intensity walking (30 min), followed by sitting (6.5 h) interrupted with 3 min of light-intensity walking every 30 min. Bilateral middle cerebral artery velocities (MCAv) were determined using transcranial Doppler at 13 time points across the day. The temporal pattern and average MCAv over 8 h was determined. The pattern of MCAv over 8 h was a negative linear trend in SIT (P < 0.001), but a positive quadratic trend in EX + SIT (P < 0.001) and EX + BR (P < 0.01). Afternoon time points in SIT were lower than baseline within condition (P <= 0.001 for all). A morning dip in MCAv was observed in EX + SIT and EX + BR (P < 0.05 relative to baseline), but afternoon time points were not significantly lower than baseline. The average MCAv over 8 h was higher in EX + SIT than SIT (P = 0.007) or EX + BR (P = 0.024). Uninterrupted sitting should be avoided, and moderate-intensity exercise should be encouraged for the daily maintenance of cerebral blood flow in older adults. The clinical implications of maintaining adequate cerebral blood flow include the delivery of vital oxygen and nutrients to the brain.NEW & NOTEWORTHY: This is the first study to measure the combined effects of an exercise bout with breaks in sitting on cerebral blood velocity in older adults. Using frequent recordings over an 8-h period, we have performed a novel analysis of the pattern of cerebral blood velocity, adjusting for concurrent measures of mean arterial pressure and other potential confounders in a linear mixed effects regression. Copyright © 2019 the American Physiological Society.
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