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Träfflista för sökning "WFRF:(Lindenberger U) ;conttype:(refereed)"

Sökning: WFRF:(Lindenberger U) > Refereegranskat

  • Resultat 1-10 av 23
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  • Burzynska, A Z, et al. (författare)
  • Age-related differences in white matter microstructure : region-specific patterns of diffusivity.
  • 2010
  • Ingår i: NeuroImage. - San Diego ; Orlando, Fla : Elsevier BV. - 1053-8119 .- 1095-9572. ; 49:3, s. 2104-2112
  • Tidskriftsartikel (refereegranskat)abstract
    • We collected MRI diffusion tensor imaging data from 80 younger (20-32 years) and 63 older (60-71 years) healthy adults. Tract-based spatial statistics (TBSS) analysis revealed that white matter integrity, as indicated by decreased fractional anisotropy (FA), was disrupted in numerous structures in older compared to younger adults. These regions displayed five distinct region-specific patterns of age-related differences in other diffusivity properties: (1) increases in both radial and mean diffusivity; (2) increases in radial diffusivity; (3) no differences in parameters other than FA; (4) a decrease in axial and an increase in radial diffusivity; and (5) a decrease in axial and mean diffusivity. These patterns suggest different biological underpinnings of age-related decline in FA, such as demyelination, Wallerian degeneration, gliosis, and severe fiber loss, and may represent stages in a cascade of age-related degeneration in white matter microstructure. This first simultaneous description of age-related differences in FA, mean, axial, and radial diffusivity requires histological and functional validation as well as analyses of intermediate age groups and longitudinal samples.
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  • Burzynska, A Z, et al. (författare)
  • Microstructure of frontoparietal connections predicts cortical responsivity and working memory performance
  • 2011
  • Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 21:10, s. 2261-2271
  • Tidskriftsartikel (refereegranskat)abstract
    • We investigated how the microstructure of relevant white matter connections is associated with cortical responsivity and working memory (WM) performance by collecting diffusion tensor imaging and verbal WM functional magnetic resonance imaging data from 29 young adults. We measured cortical responsivity within the frontoparietal WM network as the difference in blood oxygenation level-dependent (BOLD) signal between 3-back and 1-back conditions. Fractional anisotropy served as an index of the integrity of the superior longitudinal fasciculi (SLF), which connect frontal and posterior regions. We found that SLF integrity is associated with better 3-back performance and greater task-related BOLD responsivity. In addition, BOLD responsivity in right premotor cortex reliably mediated the effects of SLF integrity on 3-back performance but did not uniquely predict 3-back performance after controlling for individual differences in SLF integrity. Our results suggest that task-related adjustments of local gray matter processing are conditioned by the properties of anatomical connections between relevant cortical regions. We suggest that the microarchitecture of white matter tracts influences the speed of signal transduction along axons. This in turn may affect signal summation at neural dendrites, action potential firing, and the resulting BOLD signal change and responsivity.
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  • Davies, G., et al. (författare)
  • Genetic contributions to variation in general cognitive function : a meta-analysis of genome-wide association studies in the CHARGE consortium (N=53 949)
  • 2015
  • Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 20:2, s. 183-192
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is substantially heritable across the human life course from adolescence to old age. We investigated the genetic contribution to variation in this important, health-and well-being-related trait in middle-aged and older adults. We conducted a meta-analysis of genome-wide association studies of 31 cohorts (N = 53 949) in which the participants had undertaken multiple, diverse cognitive tests. A general cognitive function phenotype was tested for, and created in each cohort by principal component analysis. We report 13 genome-wide significant single-nucleotide polymorphism (SNP) associations in three genomic regions, 6q16.1, 14q12 and 19q13.32 (best SNP and closest gene, respectively: rs10457441, P = 3.93 x 10(-9), MIR2113; rs17522122, P = 2.55 x 10(-8), AKAP6; rs10119, P = 5.67 x 10(-9), APOE/TOMM40). We report one gene-based significant association with the HMGN1 gene located on chromosome 21 (P = 1x10(-6)). These genes have previously been associated with neuropsychiatric phenotypes. Meta-analysis results are consistent with a polygenic model of inheritance. To estimate SNP-based heritability, the genome-wide complex trait analysis procedure was applied to two large cohorts, the Atherosclerosis Risk in Communities Study (N = 6617) and the Health and Retirement Study (N = 5976). The proportion of phenotypic variation accounted for by all genotyped common SNPs was 29% (s.e. = 5%) and 28% (s.e. = 7%), respectively. Using polygenic prediction analysis, similar to 1.2% of the variance in general cognitive function was predicted in the Generation Scotland cohort (N = 5487; P = 1.5 x 10(-17)). In hypothesis-driven tests, there was significant association between general cognitive function and four genes previously associated with Alzheimer's disease: TOMM40, APOE, ABCG1 and MEF2C.
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  • Davies, G., et al. (författare)
  • Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function
  • 2018
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • General cognitive function is a prominent and relatively stable human trait that is associated with many important life outcomes. We combine cognitive and genetic data from the CHARGE and COGENT consortia, and UK Biobank (total N = 300,486; age 16-102) and find 148 genome-wide significant independent loci (P < 5 × 10-8) associated with general cognitive function. Within the novel genetic loci are variants associated with neurodegenerative and neurodevelopmental disorders, physical and psychiatric illnesses, and brain structure. Gene-based analyses find 709 genes associated with general cognitive function. Expression levels across the cortex are associated with general cognitive function. Using polygenic scores, up to 4.3% of variance in general cognitive function is predicted in independent samples. We detect significant genetic overlap between general cognitive function, reaction time, and many health variables including eyesight, hypertension, and longevity. In conclusion we identify novel genetic loci and pathways contributing to the heritability of general cognitive function.
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  • Graham, E. K., et al. (författare)
  • Trajectories of Big Five Personality Traits: A Coordinated Analysis of 16 Longitudinal Samplesty
  • 2020
  • Ingår i: European Journal of Personality. - : SAGE Publications. - 0890-2070 .- 1099-0984. ; 34:3, s. 301-321
  • Tidskriftsartikel (refereegranskat)abstract
    • This study assessed change in self-reported Big Five personality traits. We conducted a coordinated integrative data analysis using data from 16 longitudinal samples, comprising a total sample of over 60 000 participants. We coordinated models across multiple datasets and fit identical multi-level growth models to assess and compare the extent of trait change over time. Quadratic change was assessed in a subset of samples with four or more measurement occasions. Across studies, the linear trajectory models revealed declines in conscientiousness, extraversion, and openness. Non-linear models suggested late-life increases in neuroticism. Meta-analytic summaries indicated that the fixed effects of personality change are somewhat heterogeneous and that the variability in trait change is partially explained by sample age, country of origin, and personality measurement method. We also found mixed evidence for predictors of change, specifically for sex and baseline age. This study demonstrates the importance of coordinated conceptual replications for accelerating the accumulation of robust and reliable findings in the lifespan developmental psychological sciences. (c) 2020 European Association of Personality Psychology
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  • Joshi, PK, et al. (författare)
  • Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity
  • 2017
  • Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1, s. 910-
  • Tidskriftsartikel (refereegranskat)abstract
    • Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents’ survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.
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  • Joshi, Peter K, et al. (författare)
  • Directional dominance on stature and cognition in diverse human populations
  • 2015
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 523:7561, s. 459-462
  • Tidskriftsartikel (refereegranskat)abstract
    • Homozygosity has long been associated with rare, often devastating, Mendelian disorders, and Darwin was one of the first to recognize that inbreeding reduces evolutionary fitness. However, the effect of the more distant parental relatedness that is common in modern human populations is less well understood. Genomic data now allow us to investigate the effects of homozygosity on traits of public health importance by observing contiguous homozygous segments (runs of homozygosity), which are inferred to be homozygous along their complete length. Given the low levels of genome-wide homozygosity prevalent in most human populations, information is required on very large numbers of people to provide sufficient power. Here we use runs of homozygosity to study 16 health-related quantitative traits in 354,224 individuals from 102 cohorts, and find statistically significant associations between summed runs of homozygosity and four complex traits: height, forced expiratory lung volume in one second, general cognitive ability and educational attainment (P < 1 × 10(-300), 2.1 × 10(-6), 2.5 × 10(-10) and 1.8 × 10(-10), respectively). In each case, increased homozygosity was associated with decreased trait value, equivalent to the offspring of first cousins being 1.2 cm shorter and having 10 months' less education. Similar effect sizes were found across four continental groups and populations with different degrees of genome-wide homozygosity, providing evidence that homozygosity, rather than confounding, directly contributes to phenotypic variance. Contrary to earlier reports in substantially smaller samples, no evidence was seen of an influence of genome-wide homozygosity on blood pressure and low density lipoprotein cholesterol, or ten other cardio-metabolic traits. Since directional dominance is predicted for traits under directional evolutionary selection, this study provides evidence that increased stature and cognitive function have been positively selected in human evolution, whereas many important risk factors for late-onset complex diseases may not have been.
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  • Resultat 1-10 av 23

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