| 1. |
- Bellander, Martin, et al.
(författare)
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Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the comt val158met polymorphism
- 2015
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Ingår i: Neuropsychology. - : American Psychological Association (APA). - 0894-4105 .- 1931-1559. ; 29:2, s. 247-254
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Tidskriftsartikel (refereegranskat)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. |
- Brehmer, Yvonne, et al.
(författare)
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Training-induced changes in subsequent-memory effects : No major differences among children, younger adults, and older adults
- 2016
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 131, s. 214-225
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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.
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| 3. |
- Burzynska, Agnieszka Z., et al.
(författare)
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A Scaffold for Efficiency in the Human Brain
- 2013
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Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 33:43, s. 17150-17159
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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.
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| 4. |
- Burzynska, Agnieszka Z., et al.
(författare)
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Cortical thickness is linked to executive functioning in adulthood and aging
- 2012
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Ingår i: Human Brain Mapping. - : Wiley. - 1065-9471 .- 1097-0193. ; 33:7, s. 1607-20
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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.
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| 5. |
- Bäckman, Lars, et al.
(författare)
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Linking cognitive aging to alterations in dopamine neurotransmitter functioning : Recent data and future avenues
- 2010
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Ingår i: Neuroscience and Biobehavioral Reviews. - : Elsevier BV. - 0149-7634 .- 1873-7528. ; 34:5, s. 670-677
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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.
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| 6. |
- Bäckman, Lars, et al.
(författare)
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The correlative triad among aging, dopamine, and cognition : current status and future prospects.
- 2006
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Ingår i: Neuroscience and Biobehavioral Review. - : Elsevier BV. - 0149-7634. ; 30:6, s. 791-807
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)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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| 7. |
- Ghisletta, Paolo, et al.
(författare)
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The Val/Met Polymorphism of the Brain-Derived Neurotrophic Factor (BDNF) Gene Predicts Decline in Perceptual Speed in Older Adults
- 2014
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Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 29:2, s. 384-392
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Tidskriftsartikel (refereegranskat)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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| 8. |
- Guitart-Masip, Marc, et al.
(författare)
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BOLD Variability is Related to Dopaminergic Neurotransmission and Cognitive Aging
- 2016
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 26:5, s. 2074-2083
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) losses are associated with various aging-related cognitive deficits. Typically, higher moment-to-moment brain signal variability in large-scale patterns of voxels in neocortical regions is linked to better cognitive performance and younger adult age, yet the physiological mechanisms regulating brain signal variability are unknown. We explored the relationship among adult age, DA availability, and blood oxygen level-dependent (BOLD) signal variability, while younger and older participants performed a spatial working memory (SWM) task. We quantified striatal and extrastriatal DA D1 receptor density with [C-11]SCH23390 and positron emission tomography in all participants. We found that BOLD variability in a neocortical region was negatively related to age and positively related to SWM performance. In contrast, BOLD variability in subcortical regions and bilateral hippocampus was positively related to age and slower responses, and negatively related to D1 density in caudate and dorsolateral prefrontal cortex. Furthermore, BOLD variability in neocortical regions was positively associated with task-related disengagement of the default-mode network, a network whose activation needs to be suppressed for efficient SWM processing. Our results show that age-related DA losses contribute to changes in brain signal variability in subcortical regions and suggest a potential mechanism, by which neocortical BOLD variability supports cognitive performance.
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| 9. |
- Karalija, Nina, 1984-, et al.
(författare)
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A common polymorphism in the dopamine transporter gene predicts working memory performance and in vivo dopamine integrity in aging
- 2021
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 245
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) integrity is suggested as a potential cause of individual differences in working memory (WM) performance among older adults. Still, the principal dopaminergic mechanisms giving rise to WM differences remain unspecified. Here, 61 single-nucleotide polymorphisms, located in or adjacent to various dopamine-related genes, were assessed for their links to WM performance in a sample of 1313 adults aged 61–80 years from the Berlin Aging Study II. Least Absolute Shrinkage and Selection Operator (LASSO) regression was conducted to estimate associations between polymorphisms and WM. Rs40184 in the DA transporter gene, SLC6A3, showed allelic group differences in WM, with T-carriers performing better than C homozygotes (p<0.01). This finding was replicated in an independent sample from the Cognition, Brain, and Aging study (COBRA; baseline: n = 181, ages: 64–68 years; 5-year follow up: n = 129). In COBRA, in vivo DA integrity was measured with 11C-raclopride and positron emission tomography. Notably, WM as well as in vivo DA integrity was higher for rs40184 T-carriers at baseline (p<0.05 for WM and caudate and hippocampal D2-receptor availability) and at the 5-year follow-up (p<0.05 for WM and hippocampal D2 availability). Our findings indicate that individual differences in DA transporter function contribute to differences in WM performance in old age, presumably by regulating DA availability.
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| 10. |
- Karalija, Nina, 1984-, et al.
(författare)
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C957T-mediated Variation in Ligand Affinity Affects the Association between C-11-raclopride Binding Potential and Cognition
- 2019
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Ingår i: Journal of cognitive neuroscience. - : MIT Press. - 0898-929X .- 1530-8898. ; 31:2, s. 314-325
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Tidskriftsartikel (refereegranskat)abstract
- The dopamine (DA) system plays an important role in cognition. Accordingly, normal variation in DA genes has been found to predict individual differences in cognitive performance. However, little is known of the impact of genetic differences on the link between empirical indicators of the DA system and cognition in humans. The present work used PET with C-11-raclopride to assess DA D2-receptor binding potential (BP) and links to episodic memory, working memory, and perceptual speed in 179 healthy adults aged 64-68 years. Previously, the T-allele of a DA D2-receptor single-nucleotide polymorphism, C957T, was associated with increased apparent affinity of C-11-raclopride, giving rise to higher BP values despite similar receptor density values between allelic groups. Consequently, we hypothesized that C-11-raclopride BP measures inflated by affinity rather than D2-receptor density in T-allele carriers would not be predictive of DA integrity and therefore prevent finding an association between C-11-raclopride BP and cognitive performance. In accordance with previous findings, we show that C-11-raclopride BP was increased in T-homozygotes. Importantly, C-11-raclopride BP was only associated with cognitive performance in groups with low or average ligand affinity (C-allele carriers of C957T, n = 124), but not in the high-affinity group (T-homozygotes, n = 55). The strongest C-11-raclopride BP-cognition associations and the highest level of performance were found in C-homozygotes. These findings show that genetic differences modulate the link between BP and cognition and thus have important implications for the interpretation of DA assessments with PET and C-11-raclopride in multiple disciplines ranging from cognitive neuroscience to psychiatry and neurology.
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