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1.
  • Bellander, Martin, et al. (author)
  • Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the comt val158met polymorphism
  • 2015
  • In: Neuropsychology. - : American Psychological Association (APA). - 0894-4105 .- 1931-1559. ; 29:2, s. 247-254
  • Journal article (peer-reviewed)abstract
    • Objective: Little is known about genetic contributions to individual differences in cognitive plasticity. Given that the neurotransmitter dopamine is critical for cognition and associated with cognitive plasticity, we investigated the effects of 3 polymorphisms of dopamine-related genes (LMX1A, DRD2, COMT) on baseline performance and plasticity of working memory (WM), perceptual speed, and reasoning. Method: One hundred one younger and 103 older adults underwent approximately 100 days of cognitive training, and extensive testing before and after training. We analyzed the baseline and posttest data using latent change score models. Results: For working memory, carriers of the val allele of the COMT polymorphism had lower baseline performance and larger performance gains from training than carriers of the met allele. There was no significant effect of the other genes or on other cognitive domains. Conclusions: We relate this result to available evidence indicating that met carriers perform better than val carriers in WM tasks taxing maintenance, whereas val carriers perform better at updating tasks. We suggest that val carriers may show larger training gains because updating operations carry greater potential for plasticity than maintenance operations.
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2.
  • Binnewies, Julia, et al. (author)
  • Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium
  • 2022
  • In: NeuroImage. - : Elsevier. - 2213-1582. ; 36
  • Journal article (peer-reviewed)abstract
    • Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes.Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts.Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed.Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied brain structures are only detectable in clinical populations with more severe depressive symptoms.
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3.
  • Binnewies, Julia, et al. (author)
  • Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan : a pooled analysis in the European Lifebrain consortium
  • 2023
  • In: Brain Research Bulletin. - : Elsevier. - 0361-9230 .- 1873-2747. ; 200
  • Journal article (peer-reviewed)abstract
    • Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts.Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines.Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625).Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.
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4.
  • Brehmer, Yvonne, et al. (author)
  • Training-induced changes in subsequent-memory effects : No major differences among children, younger adults, and older adults
  • 2016
  • In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 131, s. 214-225
  • Journal article (peer-reviewed)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.
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5.
  • Brose, Annette, et al. (author)
  • Adult Age Differences in Covariation of Motivation and Working Memory Performance: Contrasting Between-Person and Within-Person Findings
  • 2010
  • In: Research in Human Development. - : Informa UK Limited. - 1542-7609 .- 1542-7617. ; 7:1, s. 61-78
  • Journal article (peer-reviewed)abstract
    • Developmental theorists have proposed for a long time that the prevailing focus on stable individual differences has obstructed the discovery of short-term covariations between cognitive performance and contextual influences within individuals that may help to uncover mechanisms underlying long-term change. As an initial step to overcome this imbalance, we observed measures of motivation and working memory (WM) in 101 younger and 103 older adults across 100 occasions. Our main goals were to (1) investigate day-to-day relations between motivation and WM, (2) show that these relations differ between groups of younger and older adults, and (3) test whether the within-person and between-person structures linking motivational variables to WM are equivalent (i.e., the ergodicity assumption). The covariation between motivation and WM was generally positive in younger adults. In contrast, older adults showed reduced variability in motivation, increased variability across trials, and small reliability-adjusted correlations between motivation and WM. Within-person structures differed reliably across individuals, defying the ergodicity assumption. We discuss the implications of our findings for developmental theory and design, stressing the need to explore the effects of between-person differences in short-term covariations on long-term developmental change.
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6.
  • Brose, Annette, et al. (author)
  • Daily variability in working memory is coupled with negative affect : the role of attention and motivation
  • 2012
  • In: Emotion. - : American Psychological Association (APA). - 1528-3542 .- 1931-1516. ; 12:3, s. 605-617
  • Journal article (peer-reviewed)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.
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7.
  • Brose, Annette, et al. (author)
  • Differences in the Between-Person and Within-Person Structures of Affect Are a Matter of Degree
  • 2015
  • In: European Journal of Personality. - : SAGE Publications. - 0890-2070 .- 1099-0984. ; 29:1, s. 55-71
  • Journal article (peer-reviewed)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.
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8.
  • Brose, Annette, et al. (author)
  • Normal aging dampens the link between intrusive thoughts and negative affect in reaction to daily stressors
  • 2011
  • In: Psychology and aging. - Arlington, VA : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 26:2, s. 488-502
  • Journal article (peer-reviewed)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.
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9.
  • Burzynska, Agnieszka Z., et al. (author)
  • A Scaffold for Efficiency in the Human Brain
  • 2013
  • In: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 33:43, s. 17150-17159
  • Journal article (peer-reviewed)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.
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10.
  • Burzynska, Agnieszka Z., et al. (author)
  • Cortical thickness is linked to executive functioning in adulthood and aging
  • 2012
  • In: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 33:7, s. 1607-20
  • Journal article (peer-reviewed)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.
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11.
  • Bäckman, Lars, et al. (author)
  • Linking cognitive aging to alterations in dopamine neurotransmitter functioning : Recent data and future avenues
  • 2010
  • In: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 34:5, s. 670-677
  • Research review (peer-reviewed)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.
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12.
  • Bäckman, Lars, et al. (author)
  • The correlative triad among aging, dopamine, and cognition : current status and future prospects.
  • 2006
  • In: Neuroscience and Biobehavioral Review. - : Elsevier BV. - 0149-7634. ; 30:6, s. 791-807
  • Journal article (other academic/artistic)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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13.
  • Cabeza, Roberto, et al. (author)
  • Maintenance, reserve and compensation : the cognitive neuroscience of healthy ageing
  • 2018
  • In: Nature Reviews Neuroscience. - : Nature Publishing Group. - 1471-003X .- 1471-0048. ; 19:11, s. 701-710
  • Research review (peer-reviewed)abstract
    • Cognitive ageing research examines the cognitive abilities that are preserved and/or those that decline with advanced age. There is great individual variability in cognitive ageing trajectories. Some older adults show little decline in cognitive ability compared with young adults and are thus termed ‘optimally ageing’. By contrast, others exhibit substantial cognitive decline and may develop dementia. Human neuroimaging research has led to a number of important advances in our understanding of the neural mechanisms underlying these two outcomes. However, interpreting the age-related changes and differences in brain structure, activation and functional connectivity that this research reveals is an ongoing challenge. Ambiguous terminology is a major source of difficulty in this venture. Three terms in particular — compensation, maintenance and reserve — have been used in a number of different ways, and researchers continue to disagree about the kinds of evidence or patterns of results that are required to interpret findings related to these concepts. As such inconsistencies can impede progress in both theoretical and empirical research, here, we aim to clarify and propose consensual definitions of these terms.
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14.
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15.
  • Czernochowski, Daniela, et al. (author)
  • When binding matters: An ERP analysis of the development of recollection and familiarity in childhood
  • 2004
  • In: Bound in Memory: Insights from behavioral and neuropsychological research. - 3832228713 ; , s. 93-128
  • Book chapter (other academic/artistic)abstract
    • Dual process models of recognition memory assume that memory retrieval can be based on two distinct processes: an assessment of a context-free feeling of familiarity or on the reinstatement of specific context attributes that have been bound together to form a representation of the study episode during encoding (recollection). Recent neurophysiological evidence suggests that familiarity and recollection are mediated by different medial temporal lobe circuitries and accomplished by different binding mechanisms. The assessment of familiarity has been associated with intra-item binding mechanisms of the perirhinal cortex, whereas the explicit retrieval of specific details of a study episode depends on inter-item binding mechanisms mediated by the hippocampal formation and the prefrontal cortex. A related line of evidence for the independence of these memory processes comes from the examination of patients with selective lesions: Vargha-Khadem et al. (1997) reported three cases of early bilateral hypoxic lesions restricted to the hippocampus. Although these patients were unable to acquire and to retrieve episodic information, they were unlike most adult amnesics clearly able to acquire semantic knowledge after their injury. We examined the developmental aspects of recollection and familiarity by means of an event-related potential (ERP) study in two groups of children (6–8 years, 10–12 years) and young adults (20–29 years). Topographical differences of ERP components between the age groups were found in the memory task, but not in an auditory discrimination (oddball) task, suggesting that ERP differences between groups can be ascribed to differential memory processes rather than to general age differences. Our findings support the view of a differential development of recollection and familiarity. We discuss these findings in the light of different memory strategies in children as indicated by a generally lower performance level and a more conservative response criterion.
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16.
  • de Frias, Cindy, et al. (author)
  • Revisiting the dedifferebtion hypothesis with longitudinal multi-cohort data
  • 2007
  • In: Intelligence. ; 35, s. 381-392
  • Journal article (peer-reviewed)abstract
    • The present longitudinal multi-cohort study examines whether interindividual variability in cognitive performance and change increases in old age, and whether associations among developments of different cognitive functions increase with adult age. Multivariate multiple-group latent growth modeling was applied to data from narrow cohorts separated by five years of age. Tests assessing episodic recall, semantic knowledge, semantic fluency, and visuospatial ability were administered to 1000 non-demented adults (initially aged 35–80 years), participating in the Betula Project at three occasions over a 10-year period. Greater interindividual differences in change were noted in older age groups. Age-related increases in correlations among performance scores were noted for different cognitive measures beginning in old age, but not earlier. Our study supports a dynamic view of dedifferentiation of cognitive aging.
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17.
  • Filevich, Elisa, et al. (author)
  • Day2day : Investigating daily variability of magnetic resonance imaging measures over half a year
  • 2017
  • In: BMC Neuroscience. - : Springer Science and Business Media LLC. - 1471-2202. ; 18:1
  • Journal article (peer-reviewed)abstract
    • Background: Most studies of brain structure and function, and their relationships to cognitive ability, have relied on inter-individual variability in magnetic resonance (MR) images. Intra-individual variability is often ignored or implicitly assumed to be equivalent to the former. Testing this assumption empirically by collecting enough data on single individuals is cumbersome and costly. We collected a dataset of multiple MR sequences and behavioural covariates to quantify and characterize intra-individual variability in MR images for multiple individuals. Methods and design: Eight participants volunteered to undergo brain scanning 40-50 times over the course of 6 months. Six participants completed the full set of sessions. T1-weighted, T2*-weighted during rest, T2-weighted high-resolution hippocampus, diffusion-tensor imaging (DTI), and proton magnetic resonance spectroscopy sequences were collected, along with a rich set of stable and time-varying physical, behavioural and physiological variables. Participants did not change their lifestyle or participated in any training programs during the period of data collection. Conclusion: This imaging dataset provides a large number of MRI scans in different modalities for six participants. It enables the analysis of the time course and correlates of intra-individual variability in structural, chemical, and functional aspects of the human brain.
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18.
  • Fjell, Anders M., et al. (author)
  • Poor Self-Reported Sleep is Related to Regional Cortical Thinning in Aging but not Memory Decline-Results From the Lifebrain Consortium
  • 2021
  • In: Cerebral Cortex. - : Oxford University Press. - 1047-3211 .- 1460-2199. ; 31:4, s. 1953-1969
  • Journal article (peer-reviewed)abstract
    • We examined whether sleep quality and quantity are associated with cortical and memory changes in cognitively healthy participants across the adult lifespan. Associations between self-reported sleep parameters (Pittsburgh Sleep Quality Index, PSQI) and longitudinal cortical change were tested using five samples from the Lifebrain consortium (n = 2205, 4363 MRIs, 18-92 years). In additional analyses, we tested coherence with cell-specific gene expression maps from the Allen Human Brain Atlas, and relations to changes in memory performance. "PSQI # 1 Subjective sleep quality" and "PSQI #5 Sleep disturbances" were related to thinning of the right lateral temporal cortex, with lower quality and more disturbances being associated with faster thinning. The association with "PSQI #5 Sleep disturbances" emerged after 60 years, especially in regions with high expression of genes related to oligodendrocytes and S1 pyramidal neurons. None of the sleep scales were related to a longitudinal change in episodic memory function, suggesting that sleep-related cortical changes were independent of cognitive decline. The relationship to cortical brain change suggests that self-reported sleep parameters are relevant in lifespan studies, but small effect sizes indicate that self-reported sleep is not a good biomarker of general cortical degeneration in healthy older adults.
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19.
  • Fjell, Anders M., et al. (author)
  • Self-reported sleep relates to hippocampal atrophy across the adult lifespan : results from the Lifebrain consortium
  • 2020
  • In: Sleep. - : Oxford University Press. - 0161-8105 .- 1550-9109. ; 43:5
  • Journal article (peer-reviewed)abstract
    • Objectives: Poor sleep is associated with multiple age-related neurodegenerative and neuropsychiatric conditions. The hippocampus plays a special role in sleep and sleep-dependent cognition, and accelerated hippocampal atrophy is typically seen with higher age. Hence, it is critical to establish how the relationship between sleep and hippocampal volume loss unfolds across the adult lifespan.Methods: Self-reported sleep measures and MRI-derived hippocampal volumes were obtained from 3105 cognitively normal participants (18–90 years) from major European brain studies in the Lifebrain consortium. Hippocampal volume change was estimated from 5116 MRIs from 1299 participants for whom longitudinal MRIs were available, followed up to 11 years with a mean interval of 3.3 years. Cross-sectional analyses were repeated in a sample of 21,390 participants from the UK Biobank.Results: No cross-sectional sleep—hippocampal volume relationships were found. However, worse sleep quality, efficiency, problems, and daytime tiredness were related to greater hippocampal volume loss over time, with high scorers showing 0.22% greater annual loss than low scorers. The relationship between sleep and hippocampal atrophy did not vary across age. Simulations showed that the observed longitudinal effects were too small to be detected as age-interactions in the cross-sectional analyses.Conclusions: Worse self-reported sleep is associated with higher rates of hippocampal volume decline across the adult lifespan. This suggests that sleep is relevant to understand individual differences in hippocampal atrophy, but limited effect sizes call for cautious interpretation.
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20.
  • Fjell, Anders M., et al. (author)
  • The genetic organization of longitudinal subcortical volumetric change is stable throughout the lifespan running title: Genetics of subcortical lifespan change
  • 2021
  • In: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 10
  • Journal article (peer-reviewed)abstract
    • Development and aging of the cerebral cortex show similar topographic organization and are governed by the same genes. It is unclear whether the same is true for subcortical regions, which follow fundamentally different ontogenetic and phylogenetic principles. We tested the hypothesis that genetically governed neurodevelopmental processes can be traced throughout life by assessing to which degree brain regions that develop together continue to change together through life. Analyzing over 6000 longitudinal MRIs of the brain, we used graph theory to identify five clusters of coordinated development, indexed as patterns of correlated volumetric change in brain structures. The clusters tended to follow placement along the cranial axis in embryonic brain development, suggesting continuity from prenatal stages, and correlated with cognition. Across independent longitudinal datasets, we demonstrated that developmental clusters were conserved through life. Twin-based genetic correlations revealed distinct sets of genes governing change in each cluster. Single nucleotide polymorphisms-based analyses of 38127 cross-sectional MRIs showed a similar pattern of genetic volume-volume correlations. In conclusion, coordination of subcortical change adheres to fundamental principles of lifespan continuity and genetic organization.
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21.
  • Garrett, Douglas D., et al. (author)
  • Amphetamine modulates brain signal variability and working memory in younger and older adults
  • 2015
  • In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 112:24, s. 7593-7598
  • Journal article (peer-reviewed)abstract
    • Better-performing younger adults typically express greater brain signal variability relative to older, poorer performers. Mechanisms for age and performance-graded differences in brain dynamics have, however, not yet been uncovered. Given the age-related decline of the dopamine (DA) system in normal cognitive aging, DA neuromodulation is one plausible mechanism. Hence, agents that boost systemic DA [such as d-amphetamine (AMPH)] may help to restore deficient signal variability levels. Furthermore, despite the standard practice of counterbalancing drug session order (AMPH first vs. placebo first), it remains understudied how AMPH may interact with practice effects, possibly influencing whether DA up-regulation is functional. We examined the effects of AMPH on functional-MRI-based blood oxygen level-dependent (BOLD) signal variability (SDBOLD) in younger and older adults during a working memory task (letter n-back). Older adults expressed lower brain signal variability at placebo, but met or exceeded young adult SDBOLD levels in the presence of AMPH. Drug session order greatly moderated change-change relations between AMPH-driven SDBOLD and reaction time means (RTmean) and SDs (RTSD). Older adults who received AMPH in the first session tended to improve in RTmean and RTSD when SDBOLD was boosted on AMPH, whereas younger and older adults who received AMPH in the second session showed either a performance improvement when SDBOLD decreased (for RTmean) or no effect at all (for RTSD). The present findings support the hypothesis that age differences in brain signal variability reflect aging-induced changes in dopaminergic neuromodulation. The observed interactions among AMPH, age, and session order highlight the state-and practice-dependent neurochemical basis of human brain dynamics.
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22.
  • Ghisletta, Paolo, et al. (author)
  • On the use of growth models to study normal cognitive aging
  • 2020
  • In: International Journal of Behavioral Development. - : SAGE Publications. - 0165-0254 .- 1464-0651. ; 44:1, s. 88-96
  • Journal article (peer-reviewed)abstract
    • Growth models (GM) of the mixed-effects and latent curve varieties have become popular methodological tools in lifespan research. One of the major advantages of GM is their flexibility in studying individual differences in change. We scrutinized the change functions of GM used in five years of publications on cognitive aging. Of the 162 publications that we identified, 88% test linear or quadratic polynomials, and fewer than 5% apply functions that are nonlinear in their parameters, such as exponential decline. This apparent bias in favor of polynomial decomposition calls for exploring what conclusions about individual differences in change are likely to be drawn if one applies linear or quadratic GMs to data simulated under a conceptually and empirically plausible model of exponential cognitive decline from adulthood to old age. Hence, we set up a simulation that manipulated the rate of exponential decline, measurement reliability, number of occasions, interval width, and sample size. True rate of decline and interval width influenced results strongly, number of occasions and measurement reliability exerted a moderate effect, and the effects of sample size appeared relatively minor. Critically, our results show that fit statistics generally do not differentiate misspecified linear or quadratic models from the true exponential model. Moreover, power to detect variance in change for the linear and quadratic GMs is low, and estimates of individual differences in level and change can be highly biased by model misspecification. We encourage researchers to also consider plausible nonlinear change functions when studying behavioral development across the lifespan.
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23.
  • Ghisletta, Paolo, et al. (author)
  • The Val/Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene Predicts Decline in Perceptual Speed in Older Adults
  • 2014
  • In: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 29:2, s. 384-392
  • Journal article (peer-reviewed)abstract
    • The brain-derived neurotrophic factor (BDNF) promotes activity-dependent synaptic plasticity, and contributes to learning and memory. We investigated whether a common Val66Met missense polymorphism (rs6265) of the BDNF gene is associated with individual differences in cognitive decline (marked by perceptual speed) in old age. A total of 376 participants of the Berlin Aging Study, with a mean age of 83.9 years at first occasion, were assessed longitudinally up to 11 times across more than 13 years on the Digit-Letter task. Met carriers (n = 123, 34%) showed steeper linear decline than Val homozygotes (n = 239, 66%); the corresponding contrast explained 2.20% of the variance in change in the entire sample, and 3.41% after excluding individuals at risk for dementia. These effects were not moderated by sex or socioeconomic status. Results are consistent with the hypothesis that normal aging magnifies the effects of common genetic variation on cognitive functioning.
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24.
  • Gorbach, Tetiana, 1991-, et al. (author)
  • Longitudinal association between hippocampus atrophy and episodic-memory decline in non-demented APOE ε4 carriers
  • 2020
  • In: Alzheimer’s & Dementia: Diagnosis, Assessment & Disease Monitoring. - : John Wiley & Sons. - 2352-8729. ; 12:1
  • Journal article (peer-reviewed)abstract
    • Introduction: The apolipoprotein E (APOE) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic-memory decline in non-demented individuals remains unclear.Methods: We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium.Results: The change-change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non-carriers: N = 467, r = 0.073,P = .117). The linear relationship was significantly steeper for the carriers [t(629) =2.4, P = .013]. A similar trend toward a stronger change-change relation for carriers was seen in a subsample with more than two assessments.Discussion: These findings provide evidence for a difference in hippocampus-memory association between ε4 carriers and non-carriers, thus highlighting how genetic factors modulate the translation of the AD-related pathophysiological cascade into cognitive deficits.
  •  
25.
  • Grandy, Thomas H., et al. (author)
  • Individual alpha peak frequency is related to latent factors of general cognitive abilities
  • 2013
  • In: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 79, s. 10-18
  • Journal article (peer-reviewed)abstract
    • Some eighty years after the discovery of the human electroencephalogram (EEG) and its dominant rhythm, alpha (similar to 10 Hz), the neurophysiological functions and behavioral correlates of alpha oscillations are still under debate. Similarly, the biological mechanisms contributing to the general factor of intelligence, or g, have been under scrutiny for decades. Individual alpha frequency (IAF), a trait-like parameter of the EEG, has been found to correlate with individual differences in cognitive performance and cognitive abilities. Informed by large-scale theories of neural organization emphasizing the general functional significance of oscillatory activity, the present study replicates and extends these findings by testing the hypothesis that IAF is related to intelligence at the level of g, rather than at the level of specific cognitive abilities. Structural equation modeling allowed us to statistically control for measurement error when estimating the association between IAF and intellectual functioning. In line with our hypothesis, we found a statistically reliable and substantial correlation between IAF and g (r = .40). The magnitude of this correlation did not differ significantly between younger and older adults, and captured all of the covariation between IAF and the cognitive abilities of reasoning, memory, and perceptual speed. The observed association between IAF and g provides a parsimonious explanation for the commonly observed diffuse pattern of correlations between IAF and cognitive performance. We conclude that IAF is a marker of global architectural and functional properties of the human brain.
  •  
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