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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 .- 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.
  • Wenger, Elisabeth, et al. (författare)
  • Comparing Manual and Automatic Segmentation of Hippocampal Volumes : Reliability and Validity Issues in Younger and Older Brains
  • 2014
  • Ingår i: Human Brain Mapping. - : Wiley-Blackwell. - 1065-9471 .- 1097-0193. ; 35:8, s. 4236-4248
  • Tidskriftsartikel (refereegranskat)abstract
    • We compared hippocampal volume measures obtained by manual tracing to automatic segmentation with FreeSurfer in 44 younger (20-30 years) and 47 older (60-70 years) adults, each measured with magnetic resonance imaging (MRI) over three successive time points, separated by four months. Retest correlations over time were very high for both manual and FreeSurfer segmentations. With FreeSurfer, correlations over time were significantly lower in the older than in the younger age group, which was not the case with manual segmentation. Pearson correlations between manual and FreeSurfer estimates were sufficiently high, numerically even higher in the younger group, whereas intra-class correlation coefficient (ICC) estimates were lower in the younger than in the older group. FreeSurfer yielded higher volume estimates than manual segmentation, particularly in the younger age group. Importantly, FreeSurfer consistently overestimated hippocampal volumes independently of manually assessed volume in the younger age group, but overestimated larger volumes in the older age group to a less extent, introducing a systematic age bias in the data. Age differences in hippocampal volumes were significant with FreeSurfer, but not with manual tracing. Manual tracing resulted in a significant difference between left and right hippocampus (right > left), whereas this asymmetry effect was considerably smaller with FreeSurfer estimates. We conclude that FreeSurfer constitutes a feasible method to assess differences in hippocampal volume in young adults. FreeSurfer estimates in older age groups should, however, be interpreted with care until the automatic segmentation pipeline has been further optimized to increase validity and reliability in this age group.
  • Brehmer, Yvonne, et al. (författare)
  • Training-induced changes in subsequent-memory effects : No major differences among children, younger adults, and older adults
  • 2016
  • Ingår i: NeuroImage. - 1053-8119 .- 1095-9572. ; 131, s. 214-225
  • Tidskriftsartikel (refereegranskat)abstract
    • The neural correlates of encoding mode, or the state of forming new memory episodes, have been found to change with age and mnemonic training. However, it is unclear whether neural correlates of encoding success, termed subsequent-memory (SM) effects, also differ by age and mnemonic skill. In a multi-session training study, we investigated whether SM effects are altered by instruction and training in a mnemonic skill, and whether such alterations differ among children, younger adults, and older adults. Before and after strategy training, fMRI data were collected while participants were memorizing word pairs. In all age groups, participants receiving training showed greater performance gains than control group participants. Analysis of task-relevant regions showed training-induced reductions in SM effects in left frontal regions. Reductions in SM effects largely generalized across age and primarily reflected greater training-induced activation increases for omissions than for remembered items, indicating that training resulted in more consistent use of the mnemonic strategy. The present results reveal no major age differences in SM effects in children, younger adults, and older adults.
  • Brose, Annette, et al. (författare)
  • Daily Variability in Working Memory is Coupled With Negative Affect: The Role of Attention and Motivation
  • 2012
  • Ingår i: Emotion. - : American Psychological Association (APA). - 1528-3542 .- 1931-1516. ; 12:3, s. 605-617
  • Tidskriftsartikel (refereegranskat)abstract
    • Across days, individuals experience varying levels of negative affect, control of attention, and motivation. We investigated whether this intraindividual variability was coupled with daily fluctuations in working memory (WM) performance. In 100 days, 101 younger individuals worked on a spatial N-back task and rated negative affect, control of attention, and motivation. Results showed that individuals differed in how reliably WM performance fluctuated across days, and that subjective experiences were primarily linked to performance accuracy. WM performance was lower on days with higher levels of negative affect, reduced control of attention, and reduced task-related motivation. Thus, variables that were found to predict WM in between-subjects designs showed important relationships to WM at the within-person level. In addition, there was shared predictive variance among predictors of WM. Days with increased negative affect and reduced performance were also days with reduced control of attention and reduced motivation to work on tasks. These findings are in line with proposed mechanisms linking negative affect and cognitive performance.
  • Brose, Annette, et al. (författare)
  • Differences in the Between-Person and Within-Person Structures of Affect Are a Matter of Degree
  • 2015
  • Ingår i: European Journal of Personality. - 0890-2070 .- 1099-0984. ; 29:1, s. 55-71
  • Tidskriftsartikel (refereegranskat)abstract
    • This study tested whether the structure of affect observed on the basis of between-person (BP) differences is equivalent to the affect structures that organize the variability of affective states within persons (WP) over time. Further aims were to identify individual differences in the degree of divergence between the WP and BP structure and examine its association to dispositional and contextual variables (neuroticism, extraversion, well-being and stress). In 100 daily sessions, 101 younger adults rated their mood on the Positive and Negative Affect Schedule. Variability of five negative affect items across time was so low that they were excluded from the analyses. We thus worked with a modified negative affect subscale. WP affect structures diverged reliably from the BP structure, with individual differences in the degree of divergence. Differences in the WP structural characteristics and the degree of divergence could be predicted by well-being and stress. We conclude that BP and WP structures of affect are not equivalent and that BP and WP variation should be considered as distinct phenomena. It would be wrong, for example, to conceive of positive and negative affect as independent at the WP level, as suggested by BP findings. Yet, individual differences in WP structural characteristics are related to stable BP differences, and the degree to which individuals' affect structures diverge from the BP structure can provide important insights into intraindividual functioning.
  • Brose, Annette, et al. (författare)
  • Normal aging dampens the link between intrusive thoughts and negative affect in reaction to daily stressors
  • 2011
  • Ingår i: Psychology and aging. - Arlington, VA : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 26:2, s. 488-502
  • Tidskriftsartikel (refereegranskat)abstract
    • We charted daily variations in intrusive thoughts to gain access to adult age differences in affective reactivity to daily stressors. On 100 days, 101 younger and 103 older adults reported stressors, intrusive thoughts, and negative affect. Although increments in intrusive thoughts were similar in both age groups on days with stressors, older adults' negative affect increased less than younger adults' on such days. In addition, (a) levels of intrusive thoughts and negative affect across study time were positively associated; (b) days with increased thoughts were days with increased negative affect; and (c) experiencing above-average intrusive thoughts about stressors strengthened affective reactions to stress. Relative to younger adults, all three associations were reduced in older adults. We tentatively conclude that normal aging dampens the stress-induced link between intrusive thoughts and affect. This dampening may contribute to preserved affective well-being and reduced affective reactivity to daily stress in old age.
  • Burzynska, Agnieszka Z., et al. (författare)
  • A Scaffold for Efficiency in the Human Brain
  • 2013
  • Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 33:43, s. 17150-17159
  • Tidskriftsartikel (refereegranskat)abstract
    • The comprehensive relations between healthy adult human brain white matter(WM) microstructure and gray matter (GM) function, and their joint relations to cognitive performance, remain poorly understood. We investigated these associations in 27 younger and 28 older healthy adults by linking diffusion tensor imaging (DTI) with functional magnetic resonance imaging (fMRI) data collected during an n-back working memory task. We present a novel application of multivariate Partial Least Squares (PLS) analysis that permitted the simultaneous modeling of relations between WM integrity values from all major WM tracts and patterns of condition-related BOLD signal across all GM regions. Our results indicate that greater microstructural integrity of the major WM tracts was negatively related to condition-related blood oxygenation level-dependent (BOLD) signal in task-positive GM regions. This negative relationship suggests that better quality of structural connections allows for more efficient use of task-related GM processing resources. Individuals with more intact WM further showed greater BOLD signal increases in typical task-negative regions during fixation, and notably exhibited a balanced magnitude of BOLD response across task-positive and-negative states. Structure-function relations also predicted task performance, including accuracy and speed of responding. Finally, structure-function behavior relations reflected individual differences over and above chronological age. Our findings provide evidence for the role of WM microstructure as a scaffold for the context-relevant utilization of GM regions.
  • Burzynska, Agnieszka Z., et al. (författare)
  • Cortical thickness is linked to executive functioning in adulthood and aging
  • 2012
  • Ingår i: Human Brain Mapping. - 1065-9471 .- 1097-0193. ; 33:7, s. 1607-20
  • Tidskriftsartikel (refereegranskat)abstract
    • Executive functions that are dependent upon the frontal-parietal network decline considerably during the course of normal aging. To delineate neuroanatomical correlates of age-related executive impairment, we investigated the relation between cortical thickness and executive functioning in 73 younger (20-32 years) and 56 older (60-71 years) healthy adults. Executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). Cortical thickness was measured at each location of the cortical mantle using surface-based segmentation procedures on high-resolution T1-weighted magnetic resonance images. For regions involved in WCST performance, such as the lateral prefrontal and parietal cortices, we found that thicker cortex was related to higher accuracy. Follow-up ROI-based analyses revealed that these associations were stronger in older than in younger adults. Moreover, among older adults, high and low performers differed in cortical thickness within regions generally linked to WCST performance. Our results indicate that the structural cortical correlates of executive functioning largely overlap with previously identified functional patterns. We conclude that structural preservation of relevant brain regions is associated with higher levels of executive performance in old age, and underscore the need to consider the heterogeneity of brain aging in relation to cognitive functioning.
  • Bäckman, Lars, et al. (författare)
  • Linking cognitive aging to alterations in dopamine neurotransmitter functioning : Recent data and future avenues
  • 2010
  • Ingår i: Neuroscience and Biobehavioral Reviews. - 0149-7634 .- 1873-7528. ; 34:5, s. 670-677
  • Forskningsöversikt (refereegranskat)abstract
    • Molecular-imaging studies of dopaminergic neurotransmission measure biomarkers of dopamine (DA), such as the DA transporter and D(1) and D(2) receptor densities in the living brain. These studies indicate that individual differences in DA functions are linked to cognitive performance irrespective of age, and serve as powerful mediators of age-related decline in executive functioning, episodic memory, and perceptual speed. This focused review targets several recent findings pertaining to these relationships. Specifically, we discuss novel evidence concerning (a) the role of DA in within-person cognitive variability; (b) age-related differences in DA release during cognitive processing; (c) DA release following cognitive training in younger and older adults; and (d) the relationship between DA and task-induced functional brain activity. Based on these lines of empirical inquiry, we outline a series of avenues for future research on aging, DA, and cognition.
  • Bäckman, Lars, et al. (författare)
  • The correlative triad among aging, dopamine, and cognition : current status and future prospects.
  • 2006
  • Ingår i: Neuroscience and Biobehavioral Review. - 0149-7634. ; 30:6, s. 791-807
  • Tidskriftsartikel (övrigt vetenskapligt)abstract
    • The brain neuronal systems defined by the neurotransmitter dopamine (DA) have since long a recognized role in the regulation of motor functions. More recently, converging evidence from patient studies, animal research, pharmacological intervention, and molecular genetics indicates that DA is critically implicated also in higher-order cognitive functioning. Many cognitive functions and multiple markers of striatal and extrastriatal DA systems decline across adulthood and aging. Research examining the correlative triad among adult age, DA, and cognition has found strong support for the view that age-related DA losses are associated with age-related cognitive deficits. Future research strategies for examining the DA-cognitive aging link include assessing (a) the generality/specificity of the effects; (b) the relationship between neuromodulation and functional brain activation; and (c) the release of DA during actual task performance.
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