• Advanced quantitative methods in correlating sarcopenic muscle degeneration with lower extremity function biometrics and comorbidities

      Edmunds, Kyle; Gíslason, Magnús; Sigurðsson, Sigurður; Guðnason, Vilmundur; Harris, Tamara; Carraro, Ugo; Gargiulo, Paolo; 1 ] Reykjavik Univ, Inst Biomed & Neural Engn, Reykjavik, Iceland [ 2 ] Iceland Heart Assoc Hjartavernd, Kopavogur, Iceland Show more [ 3 ] Univ Iceland, Fac Med, Reykjavik, Iceland Show more [ 4 ] NIA, Lab Epidemiol & Populat Sci, Bethesda, MD 20892 USA Show more [ 5 ] IRRCS Fdn Osped San Camillo, Venice, Italy [ 6 ] Landspitali, Dept Rehabil, Reykjavik, Iceland (Public Library of Science, 2018-03-07)
      Sarcopenic muscular degeneration has been consistently identified as an independent risk factor for mortality in aging populations. Recent investigations have realized the quantitative potential of computed tomography (CT) image analysis to describe skeletal muscle volume and composition; however, the optimum approach to assessing these data remains debated. Current literature reports average Hounsfield unit (HU) values and/or segmented soft tissue cross-sectional areas to investigate muscle quality. However, standardized methods for CT analyses and their utility as a comorbidity index remain undefined, and no existing studies compare these methods to the assessment of entire radiodensitometric distributions. The primary aim of this study was to present a comparison of nonlinear trimodal regression analysis (NTRA) parameters of entire radiodensitometric muscle distributions against extant CT metrics and their correlation with lower extremity function (LEF) biometrics (normal/fast gait speed, timed up-and-go, and isometric leg strength) and biochemical and nutritional parameters, such as total solubilized cholesterol (SCHOL) and body mass index (BMI). Data were obtained from 3,162 subjects, aged 66-96 years, from the population-based AGES-Reykjavik Study. 1-D k-means clustering was employed to discretize each biometric and comorbidity dataset into twelve subpopulations, in accordance with Sturges' Formula for Class Selection. Dataset linear regressions were performed against eleven NTRA distribution parameters and standard CT analyses (fat/muscle cross-sectional area and average HU value). Parameters from NTRA and CT standards were analogously assembled by age and sex. Analysis of specific NTRA parameters with standard CT results showed linear correlation coefficients greater than 0.85, but multiple regression analysis of correlative NTRA parameters yielded a correlation coefficient of 0.99 (P<0.005). These results highlight the specificities of each muscle quality metric to LEF biometrics, SCHOL, and BMI, and particularly highlight the value of the connective tissue regime in this regard.
    • Associations of Quadriceps Torque Properties with Muscle Size, Attenuation, and Intramuscular Adipose Tissue in Older Adults

      Frank-Wilson, Andrew W; Chalhoub, Didier; Figueiredo, Pedro; Jónsson, Pálmi V; Siggeirsdóttir, Kristín; Sigurdsson, Sigurdur; Eiriksdottir, Gudny; Guðnason, Vilmundur; Launer, Lenore; Harris, Tamara B; et al. (Oxford University Press, 2018-07)
      BACKGROUND: Atrophy and fatty infiltration of muscle with aging are associated with fractures and falls, however, their direct associations with muscle function are not well described. It was hypothesized that participants with lower quadriceps muscle attenuation, area, and greater intramuscular adipose tissue (IMAT) will exhibit slower rates of torque development (RTD) and lower peak knee extension torques. METHODS: Data from 4,842 participants (2,041 men, 2,801 women) from the Age Gene/Environment Susceptibility Reykjavik Study (mean age 76 ± 0.1 years) with complete thigh computed tomography and isometric knee testing. Regression models were adjusted for health, behavior, and comorbidities. Muscle attenuation was further adjusted for muscle area and IMAT; muscle area adjusted for IMAT and attenuation; and IMAT adjusted for muscle area and attenuation. Standardized betas (β) indicate association effect sizes. RESULTS: In the fully-adjusted models, attenuation (men β = 0.06, 95% CI: 0.01, 0.11; women β = 0.07, 95% CI: 0.03, 0.11) and muscle area (men β = 0.13, 95% CI: 0.07, 0.19; women β = 0.10, 95% CI: 0.06, 0.15) were associated with knee RTD. Attenuation (men β = 0.12, 95% CI: 0.08, 0.16; women β = 0.12, 95% CI: 0.09, 0.16) and muscle area (men β = 0.38, 95% CI: 0.33, 0.43; women β = 0.33, 95% CI: 0.29, 0.37) were associated with peak torque. CONCLUSIONS: These data suggest that muscle attenuation and area are independently associated with RTD and peak torque; and that area and attenuation demonstrate similar contributions to RTD.
    • Dietary supplement use in the older population of Iceland and association with mortality.

      Ólafsdóttir, Birta; Gunnarsdóttir, Ingibjörg; Nikulásdóttir, Hjálmfríður; Eiríksdóttir, Guðný; Harris, Tamara B; Launer, Lenore J; Guðnason, Vilmundur; Halldórsson, Thórhallur I; Einarsdóttir, Kristjana; [ 1 ] Univ Iceland, Sch Hlth Sci, Unit Nutr Res, Eiriksgata 29, IS-101 Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 2 ] Landspitali Univ Hosp, Eiriksgata 29, IS-101 Reykjavik, Iceland [ 3 ] Iceland Heart Assoc, Holtasmari 1, IS-201 Kopavogur, Iceland Show the Organization-Enhanced name(s) [ 4 ] NIA, 31 Ctr Dr,MSC 2292, Bethesda, MD 20892 USA Show the Organization-Enhanced name(s) [ 5 ] Univ Iceland, Saemundargata 2, IS-101 Reykjavik, Iceland Show the Organization-Enhanced name(s) [ 6 ] Univ Iceland, Ctr Publ Hlth Sci, Sch Hlth Sci, Sturlugata 8, IS-101 Reykjavik, Iceland (Cambridge University Press, 2017-05)
      Dietary supplements are often used by the elderly to improve their nutritional status. However, intake above the recommended dietary levels may be detrimental, and uncertainty exists on the potential health benefits of supplementation in this population. The aim of this study was to describe supplement use among Icelandic older adults and to assess its association with total mortality and CVD-related mortality. This study used data from the Age Gene/Environment Susceptibility-Reykjavik study, which recruited 5764 participants aged 66-98 years in 2002-2006. Intake of vitamins and minerals from dietary supplements was estimated from interviews. Hazard ratios (HR) for mortality were estimated in multivariate analyses with follow-up ending in 2009. The results showed that most (77 %) of the participants used supplements. Overall, the consumption of vitamins and minerals from supplements was moderate although 22 and 14 % of users exceeded the upper recommended intake levels for vitamin B6 and Zn, respectively. Supplement users followed in general a healthier lifestyle than non-users. There were 1221 deaths including 525 CVD-related deaths during the follow-up period. When comparing multivitamin users with non-users in multivariable models, no associations with total mortality (HR 0·91; 95 % CI: 0·77, 1·08) or CVD-related mortality (HR 0·91; 95 % CI 0·70, 1·18) were observed. In conclusion, users of supplements generally lead healthier lifestyles than non-users and supplements did not confer any added advantage or harm relative to mortality risk. However, the intake of vitamin B6 and Zn from dietary supplements exceeded the recommended daily intake for almost a quarter of the supplement users.
    • Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting.

      Chauhan, Ganesh; Adams, Hieab H H; Satizabal, Claudia L; Bis, Joshua C; Teumer, Alexander; Sargurupremraj, Muralidharan; Hofer, Edith; Trompet, Stella; Hilal, Saima; Smith, Albert Vernon; et al. (Lippincott Williams & Wilkins, 2019-01-16)
      To explore genetic and lifestyle risk factors of MRI-defined brain infarcts (BI) in large population-based cohorts. We performed meta-analyses of genome-wide association studies (GWAS) and examined associations of vascular risk factors and their genetic risk scores (GRS) with MRI-defined BI and a subset of BI, namely, small subcortical BI (SSBI), in 18 population-based cohorts (n = 20,949) from 5 ethnicities (3,726 with BI, 2,021 with SSBI). Top loci were followed up in 7 population-based cohorts (n = 6,862; 1,483 with BI, 630 with SBBI), and we tested associations with related phenotypes including ischemic stroke and pathologically defined BI. The mean prevalence was 17.7% for BI and 10.5% for SSBI, steeply rising after age 65. Two loci showed genome-wide significant association with BI: FBN2, In this multiethnic GWAS meta-analysis, including over 20,000 population-based participants, we identified genetic risk loci for BI requiring validation once additional large datasets become available. High BP, including genetically determined, was the most significant modifiable, causal risk factor for BI.