| 1. |
- Estrada, Karol, et al.
(författare)
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Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
- 2012
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:5, s. 491-501
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Tidskriftsartikel (refereegranskat)abstract
- Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
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| 2. |
- Savikangas, Tiina, et al.
(författare)
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The effects of a physical and cognitive training intervention vs. physical training alone on older adults' physical activity : A randomized controlled trial with extended follow-up during COVID-19
- 2021
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 16:10, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Background Executive functions underlie self-regulation and are thus important for physical activity and adaptation to new situations. The aim was to investigate, if yearlong physical and cognitive training (PTCT) had greater effects on physical activity among older adults than physical training (PT) alone, and if executive functions predicted physical activity at baseline, after six (6m) and twelve months (12m) of the interventions, one-year post-intervention follow-up and an extended follow-up during COVID-19 lockdown. Methods Data from a single-blinded, parallel-group randomized controlled trial (PASSWORD-study, ISRCTN52388040) were utilized. Participants were 70-85 years old community-dwelling men and women from Jyvaskyla, Finland. PT (n = 159) included supervised resistance, walking and balance training, home-exercises and self-administered moderate activity. PTCT (n = 155) included PT and cognitive training targeting executive functions on a computer program. Physical activity was assessed with a one-item, seven-scale question. Executive functions were assessed with color-word Stroop, Trail Making Test (TMT) B-A and Letter Fluency. Changes in physical activity were modeled with multinomial logistic models and the impact of executive functions on physical activity with latent change score models. Results No significant group-by-time interaction was observed for physical activity (p>0.1). The subjects were likely to select an activity category higher than baseline throughout the study (pooled data: B = 0.720-1.614, p<0.001-0.046). Higher baseline Stroop predicted higher physical activity through all subsequent time-points (pooled data: B = 0.011-0.013, p = 0.015-0.030). Higher baseline TMT B-A predicted higher physical activity at 6m (pooled data: B = 0.007, p = 0.006) and during COVID-19 (B = 0.005, p = 0.030). In the PT group, higher baseline Letter Fluency predicted higher physical activity at 12m (B = -0.028, p = 0.030) and follow-up (B = -0.042, p = 0.002). Conclusions Cognitive training did not have additive effects over physical training alone on physical activity, but multicomponent training and higher executive function at baseline may support adaptation to and maintenance of a physically active lifestyle among older adults.
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| 3. |
- Turunen, Katri M., et al.
(författare)
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Effects of Physical and Cognitive Training on Falls and Concern About Falling in Older Adults : Results From a Randomized Controlled Trial
- 2021
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Ingår i: The journals of gerontology. Series A, Biological sciences and medical sciences. - : Oxford University Press. - 1079-5006 .- 1758-535X. ; 77:7, s. 1430-1437
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Tidskriftsartikel (refereegranskat)abstract
- Background The aim of this study is to investigate whether combined cognitive and physical training provides additional benefits to fall prevention when compared with physical training (PT) alone in older adults. Methods This is a prespecified secondary analysis of a single-blind, randomized controlled trial involving community-dwelling men and women aged 70-85 years who did not meet the physical activity guidelines. The participants were randomized into combined physical and cognitive training (PTCT, n = 155) and PT (n = 159) groups. PT included supervised and home-based physical exercises following the physical activity recommendations. PTCT included PT and computer-based cognitive training. The outcome was the rate of falls over the 12-month intervention (PTCT, n = 151 and PT, n = 155) and 12-month postintervention follow-up (PTCT, n = 143 and PT, n = 148). Falls were ascertained from monthly diaries. Exploratory outcomes included the rate of injurious falls, faller/recurrent faller/fall-related fracture status, and concern about falling. Results Estimated incidence rates of falls per person-year were 0.8 (95% confidence interval [CI] 0.7-1.1) in the PTCT and 1.1 (95% CI 0.9-1.3) in the PT during the intervention and 0.8 (95% CI 0.7-1.0) versus 1.0 (95% CI 0.8-1.1), respectively, during the postintervention follow-up. There was no significant difference in the rate of falls during the intervention (incidence rate ratio [IRR] = 0.78; 95% CI 0.56-1.10, p = .152) or in the follow-up (IRR = 0.83; 95% CI 0.59-1.15, p = .263). No significant between-group differences were observed in any exploratory outcomes. Conclusion A yearlong PTCT intervention did not result in a significantly lower rate of falls or concern about falling than PT alone in older community-dwelling adults.
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| 4. |
- Sipilä, Sarianna, et al.
(författare)
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Promoting safe walking among older people : the effects of a physical and cognitive training intervention vs. physical training alone on mobility and falls among older community-dwelling men and women (the PASSWORD study): design and methods of a randomized controlled trial
- 2018
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Ingår i: BMC Geriatrics. - : BioMed Central. - 1471-2318. ; 18
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Tidskriftsartikel (refereegranskat)abstract
- Background: Safe and stable walking is a complex process involving the interaction of neuromuscular, sensory and cognitive functions. As physical and cognitive functions deteriorate with ageing, training of both functions may have more beneficial effects on walking and falls prevention than either alone. This article describes the study design, recruitment strategies and interventions of the PASSWORD study investigating whether a combination of physical and cognitive training (PTCT) has greater effects on walking speed, dual-task cost in walking speed, fall incidence and executive functions compared to physical training (PT) alone among 70-85-year-old community-dwelling sedentary or at most moderately physically active men and women.Methods: Community-dwelling sedentary or at most moderately physically active, men and women living in the city of Jyvaskyla will be recruited and randomized into physical training (PT) and physical and cognitive training (PTCT). The 12-month interventions include supervised training sessions and home exercises. Both groups attend physical training intervention, which follows the current physical activity guidelines. The PTCT group performes also a web-based computer program targeting executive functions. Outcomes will be assessed at baseline and at 6 and 12 months thereafter. Falls data are collected during the interventions and the subsequent one-year follow-up. The primary outcome is 10-m walking speed. Secondary outcomes include 6-min walking distance, dual-task cost in walking speed, fall incidence and executive function assessed with color Stroop and Trail Making A and B tests. Explanatory outcomes include e.g. body composition and bone characteristics, physical performance, physical activity, life-space mobility, fall-related self-efficacy, emotional well-being and personality characteristics.Discussion: The study is designed to capture the additive and possible synergistic effects of physical and cognitive training. When completed, the study will provide new knowledge on the effects of physical and cognitive training on the prevention of walking limitations and rate of falls in older people. The expected results will be of value in informing strategies designed to promote safe walking among older people and may have a significant health and socio-economic impact.
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| 5. |
- Krachler, Benno, 1966-, et al.
(författare)
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BMI and an anthropometry-based estimate of fat mass percentage are both valid discriminators of cardiometabolic risk : A comparison with DXA and bioimpedance
- 2013
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Ingår i: Journal of Obesity. - : Hindawi Publishing Corporation. - 2090-0708 .- 2090-0716. ; 2013
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To determine whether categories of obesity based on BMI and an anthropometry-based estimate of fat mass percentage (FM% equation) have similar discriminative ability for markers of cardiometabolic risk as measurements of FM% by dual-energy X-ray absorptiometry (DXA) or bioimpedance analysis (BIA).Design and Methods: A study of 40-79-year-old male (n = 205) and female (n = 388) Finns. Weight, height, blood pressure, triacylglycerols, HDL cholesterol, and fasting blood glucose were measured. Body composition was assessed by DXA and BIA and a FM%-equation.Results: For grade 1 hypertension, dyslipidaemia, and impaired fasting glucose >6.1 mmol/L, the categories of obesity as defined by BMI and the FM% equation had 1.9% to 3.7% (P < 0.01) higher discriminative power compared to DXA. For grade 2 hypertension the FM% equation discriminated 1.2% (P = 0.05) lower than DXA and 2.8% (P < 0.01) lower than BIA. Receiver operation characteristics confirmed BIA as best predictor of grade 2 hypertension and the FM% equation as best predictor of grade 1 hypertension. All other differences in area under curve were small (≤0.04) and 95% confidence intervals included 0.Conclusions: Both BMI and FM% equations may predict cardiometabolic risk with similar discriminative ability as FM% measured by DXA or BIA.
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| 6. |
- Sillanpää, Elina, et al.
(författare)
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Leukocyte and Skeletal Muscle Telomere Length and Body Composition in Monozygotic Twin Pairs Discordant for Long-term Hormone Replacement Therapy
- 2017
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Ingår i: Twin Research and Human Genetics. - Cambridge, United Kingdom : Cambridge University Press. - 1832-4274 .- 1839-2628. ; 20:2, s. 119-131
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Tidskriftsartikel (refereegranskat)abstract
- Estrogen-based hormone replacement therapy (HRT) may be associated with deceleration of cellular aging. We investigated whether long-term HRT has effects on leukocyte (LTL) or mean and minimum skeletal muscle telomere length (SMTL) in a design that controls for genotype and childhood environment. Associations between telomeres, body composition, and physical performance were also examined. Eleven monozygotic twin pairs (age 57.6 ± 1.8 years) discordant for HRT were studied. Mean duration of HRT use was 7.3 ± 3.7 years in the user sister, while their co-twins had never used HRT. LTL was measured by qPCR and SMTLs by southern blot. Body and muscle composition were estimated by bioimpedance and computed tomography, respectively. Physical performance was measured by jumping height and grip strength. HRT users and non-users did not differ in LTL or mean or minimum SMTL. Within-pair correlations were high in LTL (r = 0.69, p = .020) and in mean (r = 0.74, p = .014) and minimum SMTL (r = 0.88, p = .001). Body composition and performance were better in users than non-users. In analyses of individuals, LTL was associated with BMI (r 2 = 0.30, p = .030), percentage total body (r 2 = 0.43, p = .014), and thigh (r 2 = 0.55, p = .004) fat, while minimum SMTL was associated with fat-free mass (r 2 = 0.27, p = .020) and thigh muscle area (r 2 = 0.42, p = .016). We found no associations between HRT use and telomere length. Longer LTLs were associated with lower total and regional fat, while longer minimum SMTLs were associated with higher fat-free mass and greater thigh muscle area. This suggests that telomeres measured from different tissues may have different associations with measures of body composition.
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| 7. |
- Leskinen, Tuija, et al.
(författare)
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Differences in muscle and adipose tissue gene expression and cardio-metabolic risk factors in the members of physical activity discordant twin pairs
- 2010
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Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 5:9
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Tidskriftsartikel (refereegranskat)abstract
- High physical activity/aerobic fitness predicts low morbidity and mortality. Our aim was to identify the most up-regulated gene sets related to long-term physical activity vs. inactivity in skeletal muscle and adipose tissues and to obtain further information about their link with cardio-metabolic risk factors. We studied ten same-sex twin pairs (age range 50-74 years) who had been discordant for leisure-time physical activity for 30 years. The examinations included biopsies from m. vastus lateralis and abdominal subcutaneous adipose tissue. RNA was analyzed with the genome-wide Illumina Human WG-6 v3.0 Expression BeadChip. For pathway analysis we used Gene Set Enrichment Analysis utilizing active vs. inactive co-twin gene expression ratios. Our findings showed that among the physically active members of twin pairs, as compared to their inactive co-twins, gene expression in the muscle tissue samples was chronically up-regulated for the central pathways related to energy metabolism, including oxidative phosphorylation, lipid metabolism and supportive metabolic pathways. Up-regulation of these pathways was associated in particular with aerobic fitness and high HDL cholesterol levels. In fat tissue we found physical activity-associated increases in the expression of polyunsaturated fatty acid metabolism and branched-chain amino acid degradation gene sets both of which associated with decreased 'high-risk' ectopic body fat and plasma glucose levels. Consistent with other findings, plasma lipidomics analysis showed up-regulation of the triacylglycerols containing the polyunsaturated fatty acids. Our findings identified skeletal muscle and fat tissue pathways which are associated with the long-term physical activity and reduced cardio-metabolic disease risk, including increased aerobic fitness. In particular, improved skeletal muscle oxidative energy and lipid metabolism as well as changes in adipocyte function and redistribution of body fat are associated with reduced cardio-metabolic risk.
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| 8. |
- Moayyeri, Alireza, et al.
(författare)
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Genetic determinants of heel bone properties : genome-wide association meta-analysis and replication in the GEFOS/GENOMOS consortium
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:11, s. 3054-3068
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Tidskriftsartikel (refereegranskat)abstract
- Quantitative ultrasound of the heel captures heel bone properties that independently predict fracture risk and, with bone mineral density (BMD) assessed by X-ray (DXA), may be convenient alternatives for evaluating osteoporosis and fracture risk. We performed a meta-analysis of genome-wide association (GWA) studies to assess the genetic determinants of heel broadband ultrasound attenuation (BUA; n = 14 260), velocity of sound (VOS; n = 15 514) and BMD (n = 4566) in 13 discovery cohorts. Independent replication involved seven cohorts with GWA data (in silico n = 11 452) and new genotyping in 15 cohorts (de novo n = 24 902). In combined random effects, meta-analysis of the discovery and replication cohorts, nine single nucleotide polymorphisms (SNPs) had genome-wide significant (P < 5 x 10(-8)) associations with heel bone properties. Alongside SNPs within or near previously identified osteoporosis susceptibility genes including ESR1 (6q25.1: rs4869739, rs3020331, rs2982552), SPTBN1 (2p16.2: rs11898505), RSPO3 (6q22.33: rs7741021), WNT16 (7q31.31: rs2908007), DKK1 (10q21.1: rs7902708) and GPATCH1 (19q13.11: rs10416265), we identified a new locus on chromosome 11q14.2 (rs597319 close to TMEM135, a gene recently linked to osteoblastogenesis and longevity) significantly associated with both BUA and VOS (P < 8.23 x 10(-14)). In meta-analyses involving 25 cohorts with up to 14 985 fracture cases, six of 10 SNPs associated with heel bone properties at P < 5 x 10(-6) also had the expected direction of association with any fracture (P < 0.05), including three SNPs with P < 0.005: 6q22.33 (rs7741021), 7q31.31 (rs2908007) and 10q21.1 (rs7902708). In conclusion, this GWA study reveals the effect of several genes common to central DXA-derived BMD and heel ultrasound/DXA measures and points to a new genetic locus with potential implications for better understanding of osteoporosis pathophysiology.
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| 9. |
- Sipila, Sarianna, et al.
(författare)
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Effects of physical and cognitive training on gait speed and cognition in older adults : A randomized controlled trial
- 2021
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Ingår i: Scandinavian Journal of Medicine and Science in Sports. - : Wiley-Blackwell. - 0905-7188 .- 1600-0838. ; 31:7, s. 1518-1533
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Tidskriftsartikel (refereegranskat)abstract
- Gait speed is a measure of health and functioning. Physical and cognitive determinants of gait are amenable to interventions, but best practices remain unclear. We investigated the effects of a 12-month physical and cognitive training (PTCT) on gait speed, dual-task cost in gait speed, and executive functions (EFs) compared with physical training (PT) (ISRCTN52388040). Community-dwelling older adults, who did not meet physical activity recommendations, were recruited (n = 314). PT included supervised walking/balance (once weekly) and resistance/balance training (once weekly), home exercises (2-3 times weekly), and moderate aerobic activity 150 min/week in bouts of >10 min. PTCT included the PT and computer training (CT) on EFs 15-20 min, 3-4 times weekly. The primary outcome was gait speed. Secondary outcomes were 6-min walking distance, dual-task cost in gait speed, and EF (Stroop and Trail Making B-A). The trial was completed by 93% of the participants (age 74.5 [SD3.8] years; 60% women). Mean adherence to supervised sessions was 59%-72% in PT and 62%-77% in PTCT. Home exercises and CT were performed on average 1.9 times/week. Weekly minutes spent in aerobic activities were 188 (median 169) in PT and 207 (median 180) in PTCT. No significant interactions were observed for gait speed (PTCT-PT, 0.02; 95%CI -0.03, 0.08), walking distance (-3.8; -16.9, 9.3) or dual-task cost (-0.22; -1.74, 1.30). Stroop improvement was greater after PTCT than PT (-6.9; -13.0, -0.8). Complementing physical training with EFs training is not essential for promotion of gait speed. For EF's, complementing physical training with targeted cognitive training provides additional benefit.
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