| 1. |
- Moberg, Christina, et al.
(författare)
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De unga gör helt rätt när de stämmer staten
- 2022
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Ingår i: Aftonbladet. - 1103-9000.
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Tidskriftsartikel (populärvet., debatt m.m.)abstract
- 1 620 forskare och lärare i forskarvärlden: Vi ställer oss bakom Auroras klimatkrav
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| 2. |
- Nyberg, Lars, et al.
(författare)
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Striatal dopamine D2 binding is related to frontal BOLD response during updating of long-term memory representations
- 2009
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 46:4, s. 1194-1199
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Tidskriftsartikel (refereegranskat)abstract
- Multi-modal brain imaging was used to examine the relation between individual differences in resting-state striatal dopamine D2 binding and the magnitude of prefrontal BOLD activation during updating of long-term memory (LTM) representations. Increased activity in the left prefrontal cortex was observed when LTM updating was required, and there was a positive correlation between striatal D2 activity and the magnitude of left prefrontal activity during updating. These findings support predictions from neurocomputational models of a relation of dopaminergic neurotransmission to transient cognitive operations and related brain activity.
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| 3. |
- Bergman, Olle, 1978, et al.
(författare)
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Do polymorphisms in transcription factors LMX1A and LMX1B influence the risk for Parkinson's disease?
- 2009
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Ingår i: Journal of neural transmission (Vienna, Austria : 1996). - : Springer Science and Business Media LLC. - 1435-1463 .- 0300-9564. ; 116:3, s. 333-8
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Tidskriftsartikel (refereegranskat)abstract
- The key symptoms of Parkinson's disease (PD) are caused by degeneration of dopamine neurons originating in substantia nigra. Whereas, transcription factor LMX1A is crucial for the differentiation of mesencephalic dopamine neurons, LMX1B appears to be important for both the development and the survival of these cells. The aim of this study was to investigate if genetic variation in LMX1A and LMX1B differs between patients with PD (n = 357) and control subjects (n = 1428) by genotyping 33 single nucleotide polymorphisms (SNPs) in LMX1A and 11 SNPs in LMX1B. Three SNPs in LMX1A and one in LMX1B were associated with PD. After splitting for gender, six SNPs were associated with PD in women and four in men. The significances obtained did not survive correction for multiple testing, and our results should hence be interpreted with caution, but are partly in line with a previous report, and should thus be of sufficient interest to encourage further studies of these genes in PD.
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| 4. |
- Bäckman, Lars, et al.
(författare)
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Dopamine and cognitive aging : a strong relationship
- 2006
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Ingår i: Progress in psychological science around the world. Volume 1 neural, cognitive and developmental issues. - : Psychology Press. - 9780203783122 - 9781841699615 - 9781138883314 ; , s. 455-469
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Konferensbidrag (refereegranskat)
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| 5. |
- Bäckman, Lars, et al.
(författare)
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Dopamine D(1) receptors and age differences in brain activation during working memory
- 2011
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Ingår i: Neurobiology of Aging. - Fayetteville, N.Y : Elsevier. - 0197-4580 .- 1558-1497. ; 32:10, s. 1849-1856
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Tidskriftsartikel (refereegranskat)abstract
- In an fMRI study, 20 younger and 20 healthy older adults were scanned while performing a spatial working-memory task under two levels of load. On a separate occasion, the same subjects underwent PET measurements using the radioligand [(11)C] SCH23390 to determine dopamine D(1) receptor binding potential (BP) in caudate nucleus and dorsolateral prefrontal cortex (DLPFC). The fMRI study revealed a significant load modulation of brain activity (higher load>lower load) in frontal and parietal regions for younger, but not older, adults. The PET measurements showed marked age-related reductions of D(1) BP in caudate and DLPFC. Statistical control of caudate and DLPFC D(1) binding eliminated the age-related reduction in load-dependent BOLD signal in left frontal cortex, and attenuated greatly the reduction in right frontal and left parietal cortex. These findings suggest that age-related alterations in dopaminergic neurotransmission may contribute to underrecruitment of task-relevant brain regions during working-memory performance in old age.
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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. |
- de Frias, Cindy M., et al.
(författare)
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Influence of COMT Gene Polymorphism on fMRI-assessed Sustained and Transient Activity during a Working Memory Task
- 2010
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Ingår i: Journal of cognitive neuroscience. - Cambridge, Mass. : MIT Press. - 0898-929X .- 1530-8898. ; 22:7, s. 1614-1622
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Tidskriftsartikel (refereegranskat)abstract
- The catechol O-methyltransferase (COMT) gene-encoding an enzyme that is essential for the degradation of dopamine (DA) in prefrontal cortex (PFC)-contains a single nucleotide polymorphism (val/met) important for cognition. According to the tonic-phasic hypothesis, individuals carrying the low-enzyme- activity allele (met) are characterized by enhanced tonic DA activity in PFC, promoting sustained cognitive representations in working memory. Val carriers have reduced tonic but enhanced phasic dopaminergic activity in subcortical regions, enhancing cognitive flexibility. We tested the tonic-phasic DA hypothesis by dissociating sustained and transient brain activity during performance on a 2-back working memory test using mixed blocked/event-related functional magnetic resonance imaging. Participants were men recruited from a random sample of the population (the Betula study) and consisted of 11 met/met and 11 val/val carriers aged 50 to 65 years, matched on age, education, and cognitive performance. There were no differences in 2-back performance between genotype groups. Met carriers displayed a greater transient medial temporal lobe response in the updating phase of working memory, whereas val carriers showed a greater sustained PFC activation in the maintenance phase. These results support the tonic-phasic theory of DA function in elucidating the specific phenotypic influence of the COMT val(158)met polymorphism on different components of working memory.
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| 8. |
- Ferreira, Daniel, et al.
(författare)
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The interactive effect of demographic and clinical factors on hippocampal volume : A multicohort study on 1958 cognitively normal individuals
- 2017
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Ingår i: Hippocampus. - : Wiley. - 1050-9631 .- 1098-1063. ; 27:6, s. 653-667
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Tidskriftsartikel (refereegranskat)abstract
- Alzheimer's disease is characterized by hippocampal atrophy. Other factors also influence the hippocampal volume, but their interactive effect has not been investigated before in cognitively healthy individuals. The aim of this study is to evaluate the interactive effect of key demographic and clinical factors on hippocampal volume, in contrast to previous studies frequently investigating these factors in a separate manner. Also, to investigate how comparable the control groups from ADNI, AIBL, and AddNeuroMed are with five population-based cohorts. In this study, 1958 participants were included (100 AddNeuroMed, 226 ADNI, 155 AIBL, 59 BRC, 295 GENIC, 279 BioFiNDER, 398 PIVUS, and 446 SNAC-K). ANOVA and random forest were used for testing between-cohort differences in demographic-clinical variables. Multiple regression was used to study the influence of demographic-clinical variables on hippocampal volume. ANCOVA was used to analyze whether between-cohort differences in demographic-clinical variables explained between-cohort differences in hippocampal volume. Age and global brain atrophy were the most important variables in explaining variability in hippocampal volume. These variables were not only important themselves but also in interaction with gender, education, MMSE, and total intracranial volume. AddNeuroMed, ADNI, and AIBL differed from the population-based cohorts in several demographic-clinical variables that had a significant effect on hippocampal volume. Variability in hippocampal volume in individuals with normal cognition is high. Differences that previously tended to be related to disease mechanisms could also be partly explained by demographic and clinical factors independent from the disease. Furthermore, cognitively normal individuals especially from ADNI and AIBL are not representative of the general population. These findings may have important implications for future research and clinical trials, translating imaging biomarkers to the general population, and validating current diagnostic criteria for Alzheimer's disease and predementia stages.
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| 9. |
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| 10. |
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| 11. |
- Jonasson, Lars S., et al.
(författare)
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Dopamine release in nucleus accumbens during rewarded task switching measured by [C-11]raclopride
- 2014
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 99, s. 357-364
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Tidskriftsartikel (refereegranskat)abstract
- Reward and motivation have positive influences on cognitive-control processes in numerous settings. Models of reward implicate corticostriatal loops and the dopamine (DA) system, with special emphasis on D-2 receptors in nucleus accumbens (NAcc). In this study, 11 right-handed males (35-40 years) were scanned with positron emission tomography (PET) in a single [C-11]raclopride dynamic scan during rewarded and non-rewarded task switching. Rewarded task switching (relative to baseline task switching) decreased [11C]raclopride binding in NAcc. Decreasing NAcc [C-11]raclopride binding was strongly associated with task reaction time measures that reflect individual differences in effort and control strategies. Voxelwise analyses additionally revealed reward-related DA release in anterodorsal caudate, a region previously associated with task-switching. These PET findings provide evidence for striatal DA release during motivated cognitive control, and further suggest that NAcc DA release predicts the task reaction time benefits of reward incentives.
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| 12. |
- 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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| 13. |
- Karlsson, Sari, et al.
(författare)
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Modulation of striatal dopamine D1 binding by cognitive processing
- 2009
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 48:2, s. 398-404
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Tidskriftsartikel (refereegranskat)abstract
- There is strong evidence that dopamine (DA) is implicated in higher-order cognitive functioning, but it remains controversial whether D1 receptor binding can be modified by cognitive activity. We examined striatal D1 binding potential (BP) in 20 younger (22-30 years) and 20 older (65-75 years) persons who underwent two [(11)C] SCH 23390 PET measurements, one while resting and one while performing a cognitive task taxing inhibitory functioning. The younger persons showed significant task-related BP reductions in sensorimotor, limbic, and associative striatum during cognitive activity compared to rest. Older persons showed no reliable BP reductions in any striatal subregion. These findings demonstrate that D1 receptor binding can be modified by cognitive activity in younger persons, but also provide novel evidence for the notion that human aging is associated not only with lower DA receptor density but also with altered modifiability of the DA system.
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| 14. |
- Karlsson, Sari, et al.
(författare)
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Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans
- 2011
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Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 57:2, s. 346-351
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) availability in both striatal and extrastriatal brain regions has been implicated in cognitive performance. Given that different brain regions are neuroanatomically and functionally different, DA receptor binding in different brain regions may be selectively important to specific cognitive functions. Using PET and the radioligand SCH23390, we measured D1 receptor binding potential (BP(ND)) in dorsolateral prefrontal cortex (DLPFC), hippocampus (HC), as well as in sensorimotor (SMST), associative (AST), and limbic (LST) striatum in 20 healthy younger persons. Subjects completed tasks assessing executive functioning, episodic memory, speed, and general knowledge. Unlike previous reports, we found no linear or curvilinear relationships between D1 receptor binding in DLPFC and performance in any cognitive task. However, BP(ND) in HC was positively linked to executive performance as well as to speed and knowledge. With regard to the striatal subregions, D1 BP(ND) in SMST was more strongly related to speed compared to the other striatal subregions, whereas D1 BP(ND) in AST was more strongly linked to general knowledge. These findings provide support for the notion that D1 receptors in separate brain regions are differentially related to performance in tasks tapping various cognitive domains.
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| 15. |
- Köhncke, Ylva, et al.
(författare)
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Self-rated intensity of habitual physical activities is positively associated with dopamine D-2/3 receptor availability and cognition
- 2018
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 181, s. 605-616
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Tidskriftsartikel (refereegranskat)abstract
- Between-person differences in cognitive performance in older age are associated with variations in physical activity. The neurotransmitter dopamine (DA) contributes to cognitive performance, and the DA system deteriorates with advancing age. Animal data and a patient study suggest that physical activity modulates DA receptor availability, but data from healthy humans are lacking. In a cross-sectional study with 178 adults aged 64-68 years, we investigated links among self-reported physical activity, D(2/3)DA receptor (D2/3DR) availability, and cognitive performance. D2/3DR availability was measured with [C-11]raclopride positron emission tomography at rest. We used structural equation modeling to obtain latent factors for processing speed, episodic memory, working memory, physical activity, and D2/3DR availability in caudate, putamen, and hippocampus. Physical activity intensity was positively associated with D2/3DR availability in caudate, but not putamen and hippocampus. Frequency of physical activity was not related to D2/3DR availability. Physical activity intensity was positively related to episodic memory and working memory. D2/3DR availability in caudate and hippocampus was positively related to episodic memory. Taken together, our results suggest that striatal DA availability might be a neurochemical correlate of episodic memory that is also associated with physical activity.
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| 16. |
- Lind, Johanna, et al.
(författare)
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Reduced functional brain activity response in cognitively intact apolipoprotein E ε4 carriers
- 2006
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Ingår i: Brain. - : Oxford University Press. - 0006-8950 .- 1460-2156. ; 129:5, s. 1240-1248
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Tidskriftsartikel (refereegranskat)abstract
- The apolipoprotein E epsilon4 (APOE epsilon4) is the main known genetic risk factor for Alzheimer's disease. Genetic assessments in combination with other diagnostic tools, such as neuroimaging, have the potential to facilitate early diagnosis. In this large-scale functional MRI (fMRI) study, we have contrasted 30 APOE epsilon4 carriers (age range: 49-74 years; 19 females), of which 10 were homozygous for the epsilon4 allele, and 30 non-carriers with regard to brain activity during a semantic categorization task. Test groups were closely matched for sex, age and education. Critically, both groups were cognitively intact and thus symptom-free of Alzheimer's disease. APOE epsilon4 carriers showed reduced task-related responses in the left inferior parietal cortex, and bilaterally in the anterior cingulate region. A dose-related response was observed in the parietal area such that diminution was most pronounced in homozygous compared with heterozygous carriers. In addition, contrasts of processing novel versus familiar items revealed an abnormal response in the right hippocampus in the APOE epsilon4 group, mainly expressed as diminished sensitivity to the relative novelty of stimuli. Collectively, these findings indicate that genetic risk translates into reduced functional brain activity, in regions pertinent to Alzheimer's disease, well before alterations can be detected at the behavioural level.
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| 17. |
- Lind, Johanna, et al.
(författare)
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Reduced hippocampal volume in non-demented carriers fo the apolipoprotein E ε4 : Relation to chronological age and recognition memory
- 2006
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Ingår i: Neuroscience Letters. - : Elsevier BV. - 0304-3940 .- 1872-7972. ; 396:1, s. 23-27
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Tidskriftsartikel (refereegranskat)abstract
- Apolipoprotein E ε4 (APOE ε4) is the main known genetic risk factor for Alzheimer's disease (AD). Some previous studies have reported structural brain changes as well as cognitive deficits in non-demented APOE ε4 carriers, but the pattern of results is inconsistent and studies with larger sample sizes have been called for. Here we compared hippocampal volume and recognition–memory performance between AD-symptom-free carriers (N = 30) and non-carriers (N = 30) of the APOE ε4 (age range: 49–79 years). We observed reduced right hippocampal volume in APOE ε4 carriers, and found that the difference was most pronounced before the age of 65. Further, the APOE ε4 carriers made significantly more false alarms in the recognition–memory test, and the number of false alarms correlated significantly with right hippocampus volume. These results indicate that relatively young individuals at genetic risk for AD have smaller hippocampal volume and lower performance on hippocampal-dependent cognitive tasks. A question for the future is whether smaller hippocampal volume represents early-onset hippocampal volume reduction or an inherent trait.
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| 18. |
- Lövdén, Martin, et al.
(författare)
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Latent-Profile Analysis Reveals Behavioral and Brain Correlates of Dopamine-Cognition Associations
- 2018
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 28:11, s. 3894-3907
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Tidskriftsartikel (refereegranskat)abstract
- Evidence suggests that associations between the neurotransmitter dopamine and cognition are nonmonotonic and open to modulation by various other factors. The functional implications of a given level of dopamine may therefore differ from person to person. By applying latent-profile analysis to a large (n = 181) sample of adults aged 64-68 years, we probabilistically identified 3 subgroups that explain the multivariate associations between dopamine D2/3R availability (probed with C-11-raclopride-PET, in cortical, striatal, and hippocampal regions) and cognitive performance (episodic memory, working memory, and perceptual speed). Generally, greater receptor availability was associated with better cognitive performance. However, we discovered a subgroup of individuals for which high availability, particularly in striatum, was associated with poor performance, especially for working memory. Relative to the rest of the sample, this subgroup also had lower education, higher body-mass index, and lower resting-state connectivity between caudate nucleus and dorsolateral prefrontal cortex. We conclude that a smaller subset of individuals induces a multivariate non-linear association between dopamine D2/3R availability and cognitive performance in this group of older adults, and discuss potential reasons for these differences that await further empirical scrutiny.
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| 19. |
- MacDonald, Stuart W S, et al.
(författare)
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Extrastriatal dopamine D2 receptor binding modulates intraindividual variability in episodic recognition and executive functioning.
- 2009
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Ingår i: Neuropsychologia. - : Elsevier BV. - 0028-3932 .- 1873-3514. ; 47:11, s. 2299-2304
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Tidskriftsartikel (refereegranskat)abstract
- Intraindividual variability (IIV) reflects lawful but transient within-person changes in performance. Increased IIV in cognition shares systematic associations with numerous conditions characterized by alterations in dopamine (DA) neuromodulation (e.g., old age, ADHD, schizophrenia, and Parkinson's disease). In a group of normal middle-aged adults, we examined links between PET-derived measures of D2 receptor binding in striatum, orbitofrontal cortex (OFC), anterior cingulate cortex (ACC), and hippocampus (HC) and IIV for tasks assessing recognition memory and executive functioning. An index of IIV, the intraindividual standard deviation (ISD), was computed across successful response latency trials for each cognitive outcome. Lower D2 binding in OC, ACC, and HC, but not striatum, was associated with increasing ISDs for the memory and executive measures. Consistent with neurocomputational models, the present findings suggest a role for extrastriatal DA neurotransmission in modulating variability in cognitive functioning.
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| 20. |
- Maitland, Scott B., et al.
(författare)
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On the structure of personality : Are there separate temperament and character factors?
- 2009
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Ingår i: Personality and Individual Differences. - : Elsevier. - 0191-8869 .- 1873-3549. ; 47:3, s. 180-184
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Tidskriftsartikel (refereegranskat)abstract
- The Temperament and Character Inventory (TCI) is a widely used measure of psychobiological aspects of personality. Theoretically, the TCI is defined as comprising four temperament and three character factors. Most previous examinations of the factor structure have used exploratory factor methods with mixed results. We used confirmatory factor analyses (CFA) to examine the TCI in a sample of 2423 adults aged 35–90 years (1093 women, 1330 men) from the Betula study. Support for the seven TCI factors was mixed. Models including second-order factors provided no evidence that the seven first-order TCI factors reflect higher-order temperament and character constructs. Our findings provide no support that individual differences on the seven first-order TCI factors reflect distinct temperament or character dimensions of personality. Whereas more complex modeling strategies rejected separate character and temperament models, the simultaneous (seven-factor) model, and the use of second-order factors; the harm avoidance, self-directedness, and cooperativeness factors were acceptable examined individually. Results for novelty seeking were marginal and self-transcendence, reward dependence and/or persistence factors were not acceptable.
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| 21. |
- Maitland, Scott B, et al.
(författare)
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Selective sex differences in declarative memory.
- 2004
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Ingår i: Mem Cognit. - : Springer Science and Business Media LLC. - 0090-502X .- 1532-5946. ; 32:7, s. 1160-9
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Tidskriftsartikel (refereegranskat)abstract
- Sex invariance of a six-factor, higher order model of declarative memory (two second-order factors: episodic and semantic memory; and four first-order factors: recall, recognition, fluency, and knowledge) was established for 1,796 participants (35-85 years). Metric invariance of first- and second-order factor loadings across sex was demonstrated. At the second-order level, a female advantage was observed for both episodic and semantic memory. At the first-order level, sex differences in episodic memory were apparent for both recall and recognition, whereas the differences in semantic memory were driven by a female superiority in fluency. Additional tests of sex differences in three age groups (35-50, 55-65, and 70-85 years of age) indicated that the female superiority in declarative memory diminished with advancing age. The factor-specific sex differences are discussed in relation to sex differences in hippocampal function.
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| 22. |
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| 23. |
- Nilsson, Lars-Göran, et al.
(författare)
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Betula : a prospective cohort study on memory, health and aging
- 2004
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Ingår i: Aging, Neuropsychology and Cognition. - Hove : Psychology Press. - 1382-5585 .- 1744-4128. ; 11:2-3, s. 134-148
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Tidskriftsartikel (refereegranskat)abstract
- This article describes the Betula Study with respect to objectives, design, participants, and assessment instruments for health and cognition. Three waves of data collection have been completed in 5-year intervals since 1988-1990. A fourth wave started in 2003 and will be completed in 2005. An overview of Betula research is presented under the headings of memory and cognition and cognitive neuroscience. Health-related issues and sex differences as well as comparisons between cross-sectional and longitudinal studies are discussed in the first section. The influence of different genes and of some brain abnormalities for memory functioning in adulthood and old age constitute main topics in the second section. New data are presented on the association between blood pressure and dementia. We demonstrated that a demented group of participants had higher levels of systolic blood pressure and pulse pressure than non-dementia controls 10 years before diagnosis. The new fourth wave of data collection will, in addition to enriching the Betula database, permit revisiting and reanalyzing the existing data from new perspectives.
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| 24. |
- Nilsson, Lars-Göran, et al.
(författare)
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The influence of APOE status on episodic and semantic memory : data from a population-based study
- 2006
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Ingår i: Neuropsychology. - Washington : American Psychological Association. - 0894-4105 .- 1931-1559. ; 20:6, s. 645-57
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Tidskriftsartikel (refereegranskat)abstract
- In a prospective cohort study, the authors demonstrated a more pronounced epsilon4-related deficit for participants 70 years of age and older in tasks assessing episodic recall. Apolipoprotein E (APOE) and age interacted for episodic memory tasks, whereas the interaction for semantic memory tasks was between APOE and test wave. Heterozygotes of epsilon4 between middle-age and young-old participants performed at a higher level than noncarriers of this allele in recall tasks. A dose effect was found such that carriers of 2 epsilon4 alleles failed more profoundly in acquiring and recollecting episodic information than carriers of 1 epsilon4 allele, who in turn failed more than carriers of non-epsilon4 alleles. The pattern of findings observed for older epsilon4 carriers suggests that these individuals have particular difficulty when the executive task demands are high. Several factors (e.g., smaller hippocampal volumes, less effective neural repair mechanisms) may account for these findings. On the basis of the data obtained, the authors argue that analyses of the effect of specific genes in cognition should be accompanied by assessment of performance at a specific level, with due attention to the individual's age.
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| 25. |
- Plaven-Sigray, Pontus, et al.
(författare)
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Dopamine D1 receptor availability is related to social behavior : A positron emission tomography study
- 2014
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Ingår i: NeuroImage. - : Elsevier BV. - 1053-8119 .- 1095-9572. ; 102, s. 590-595
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Tidskriftsartikel (refereegranskat)abstract
- Dysfunctional interpersonal behavior is thought to underlie a wide spectrum of psychiatric disorders; however, the neurobiological underpinnings of these behavioral disturbances are poorly understood. Previous molecular imaging studies have shown associations between striatal dopamine (DA) D2-receptor binding and interpersonal traits, such as social conformity. The objective of this study was to explore, for the first time, the role of DA D1-receptors (D1-Rs) in human interpersonal behavior. Twenty-three healthy subjects were examined using positron emission tomography and the radioligand [C-11] SCH23390, yielding D1-R binding potential values. Striatal D1-R binding was related to personality scales selected to specifically assess one dimension of interpersonal behavior, namely a combination of affiliation and dominance (i.e., the Social Desirability, Verbal Trait Aggression and Physical Trait Aggression scales from Swedish Universities Scales of Personality). An exploratory analysis was also performed for extrastriatal brain regions. D1-R binding potential values in the limbic striatum(r= .52; p= .015), associative striatum(r= .55; p= .009), and sensorimotor striatum(r= .67; p= .001) were positively related to Social Desirability scores. D1-R binding potential in the limbic striatum (r= -.51; p = .019) was negatively associated with Physical Trait Aggression scores. For extrastriatal regions, Social Desirability scores showed positive correlations in the amygdala (r = .60; p = .006) and medial frontal cortex (r= .60; p = .004). This study provides further support for the role of DA function in the expression of disaffiliative and dominant traits. Specifically, D1-R availability may serve as a marker for interpersonal behavior in humans. Associations were demonstrated for the same dimension of interpersonal behavior as for D2-R, but in the opposite direction, suggesting that the two receptor subtypes are involved in the same behavioral processes, but with different functional roles.
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| 26. |
- Rieckmann, Anna, et al.
(författare)
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Dopamine D1 Receptor Associations within and between Dopaminergic Pathways in Younger and Elderly Adults : Links to Cognitive Performance
- 2011
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Ingår i: Cerebral Cortex. - Oxford : Oxford University Press. - 1047-3211 .- 1460-2199. ; 21:9, s. 2023-2032
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Tidskriftsartikel (refereegranskat)abstract
- Age-related dopamine (DA) losses have been extensively demonstrated for the D2 receptor subtype. Comparatively little is known about adult age changes regarding D1 receptors. In this study, we demonstrate marked age-related D1 receptor losses in striatal, limbic, and cortical areas using positron emission tomography and the radioligand [11C]SCH23390 in humans. Interregional correlations of binding potential (BP) values were high for areas within DA pathways in younger and elderly adults alike. Furthermore, interregional correlations in D1 BP between DA pathways were uniformly high in younger adults, indicating that D1 receptor densities in striatal, limbic, and cortical areas are not regulated independently, despite dopaminergic innervation from different midbrain areas. For elderly adults, between-pathway correlations of D1 receptor densities were preserved only between mesolimbic and mesocortical areas, whereas striatal BPs were weakly related to those in limbic and neocortical regions. Importantly, weak between-pathway correlations in elderly adults were found only for the slower half of the sample when BP was estimated during a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in older age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing.
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| 27. |
- Rönnlund, Michael, et al.
(författare)
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Stability, Growth, and Decline in Adult Life Span Development of Declarative Memory : Cross-Sectional and Longitudinal Data From a Population-Based Study
- 2005
-
Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 20:1, s. 3-18
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Tidskriftsartikel (refereegranskat)abstract
- Five-year changes in episodic and semantic memory were examined in a sample of 829 participants (35-80 years). A cohort-matched sample (N=967) was assessed to control for practice effects. For episodic memory, cross-sectional analyses indicated gradual age-related decrements, whereas the longitudinal data revealed no decrements before age 60, even when practice effects were adjusted for. Longitudinally, semantic memory showed minor increments until age 55, with smaller decrements in old age as compared with episodic memory. Cohort differences in educational attainment appear to account for the discrepancies between cross-sectional and longitudinal data. Collectively, the results show that age trajectories for episodic and semantic memory differ and underscore the need to control for cohort and retest effects in cross-sectional and longitudinal studies, respectively.
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| 28. |
- Salami, Alireza, et al.
(författare)
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Dopamine D-2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion
- 2019
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 39:3, s. 537-547
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) modulates corticostriatal connections. Studies in which imaging of the DA system is integrated with functional imaging during cognitive performance have yielded mixed findings. Some work has shown a link between striatal DA(measured by PET) and fMRI activations, whereas others have failed to observe such a relationship. One possible reason for these discrepant findings is differences in task demands, such that a more demanding task with greater prefrontal activations may yield a stronger association with DA. Moreover, a potential DA-BOLD association may be modulated by task performance. We studied 155 (104 normal-performing and 51 low-performing) healthy older adults (43% females) who underwent fMRI scanning while performing a working memory (WM) n-back task along with DA D-2/3 PET assessment using [C-11] raclopride. Using multivariate partial-least-squares analysis, we observed a significant pattern revealing positive associations of striatal as well as extrastriatal DA D-2/3 receptors to BOLD response in the thalamo-striatalcortical circuit, which supports WM functioning. Critically, the DA-BOLD association in normal-performing, but not low-performing, individuals was expressed in a load-dependent fashion, with stronger associations during 3-back than 1-/2-back conditions. Moreover, normal-performing adults expressing upregulated BOLD in response to increasing task demands showed a stronger DA-BOLD association during 3-back, whereas low-performing individuals expressed a stronger association during 2-back conditions. This pattern suggests a nonlinear DA-BOLD performance association, with the strongest link at the maximum capacity level. Together, our results suggest that DA may have a stronger impact on functional brain responses during more demanding cognitive tasks.
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| 29. |
- Alakurtti, Kati, et al.
(författare)
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Long-term test-retest reliability of striatal and extrastriatal dopamine D-2/3 receptor binding : study with [C-11]raclopride and high-resolution PET
- 2015
-
Ingår i: Journal of Cerebral Blood Flow and Metabolism. - : SAGE Publications. - 0271-678X .- 1559-7016. ; 35:7, s. 1199-1205
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Tidskriftsartikel (refereegranskat)abstract
- We measured the long-term test-retest reliability of [C-11]raclopride binding in striatal subregions, the thalamus and the cortex using the bolus-plus-infusion method and a high-resolution positron emission scanner. Seven healthy male volunteers underwent two positron emission tomography (PET) [C-11]raclopride assessments, with a 5-week retest interval. D-2/3 receptor availability was quantified as binding potential using the simplified reference tissue model. Absolute variability (VAR) and intraclass correlation coefficient (ICC) values indicated very good reproducibility for the striatum and were 4.5%/0.82, 3.9%/0.83, and 3.9%/0.82, for the caudate nucleus, putamen, and ventral striatum, respectively. Thalamic reliability was also very good, with VAR of 3.7% and ICC of 0.92. Test-retest data for cortical areas showed good to moderate reproducibility (6.1% to 13.1%). Our results are in line with previous test-retest studies of [C-11]raclopride binding in the striatum. A novel finding is the relatively low variability of [C-11]raclopride binding, providing suggestive evidence that extrastriatal D-2/3 binding can be studied in vivo with [C-11]raclopride PET to be verified in future studies.
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| 30. |
- Arvidsson, Eva, 1959-, et al.
(författare)
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Vägen framåt
- 2013
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Ingår i: Att välja rättvist. - Lund : Studentlitteratur AB. ; , s. 207-214
-
Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Som vi visat har utvecklingen av metoder och strukturer för öppna prioriteringar i Sverige kommit långt. Många frågor återstår likväl. Under vårt arbete med denna bok har vi identifierat ett antal förbättringsområden och utmaningar som vi avslutningsvis vill lyfta fram. Det rör sig om vilka som ska delta i prioriteringarna, tydliggörande av värdegrunden, behov av bättre kunskap, baserad på både vetenskaplig metod och erfarenhet, och fortsatt utveckling av prioriteringsprocesser på olika nivåer och i olika sammanhang. Även om vi i Sverige skulle nå en god enighet kring principer och kriterier för prioriteringar så kommer vi alltid finna många olika sätt att praktiskt lösa specifika prioriteringsproblem.
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| 31. |
- Avelar-Pereira, Barbara, et al.
(författare)
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Increased functional homotopy of the prefrontal cortex is associated with corpus callosum degeneration and working memory decline
- 2020
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Ingår i: Neurobiology of Aging. - : Elsevier. - 0197-4580 .- 1558-1497. ; 96, s. 68-78
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Tidskriftsartikel (refereegranskat)abstract
- Functional homotopy reflects the link between spontaneous activity in a voxel and its counterpart in the opposite hemisphere. Alterations in homotopic functional connectivity (FC) are seen in normal aging, with highest and lowest homotopy being present in sensory-motor and higher-order regions, respectively. Homotopic FC relates to underlying structural connections, but its neurobiological underpinnings remain unclear. The genu of the corpus callosum joins symmetrical parts of the prefrontal cortex (PFC) and is susceptible to age-related degeneration, suggesting that PFC homotopic connectivity is linked to changes in white-matter integrity. We investigated homotopic connectivity changes and whether these were associated with white-matter integrity in 338 individuals. In addition, we examined whether PFC homotopic FC was related to changes in the genu over 10 years and working memory over 5 years. There were increases and decreases in functional homotopy, with the former being prevalent in subcortical and frontal regions. Increased PFC homotopic FC was partially driven by structural degeneration and negatively associated with working memory, suggesting that it reflects detrimental age-related changes. (C) 2020 The Author(s). Published by Elsevier Inc.
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| 32. |
- 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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| 33. |
- Bäckman, Lars, et al.
(författare)
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Attentional demands and recall of verbal and color information in action events
- 1993
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Ingår i: Scandinavian Journal of Psychology. - : Blackwell Publishing. - 0036-5564 .- 1467-9450. ; 34:3, s. 246-254
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Tidskriftsartikel (refereegranskat)abstract
- Two experiments addressed the influence of secondary task performance at encoding on recall of different features of subject‐performed tasks (SPTs) involving objects (e.g., turn the wallet). In Experiment 1, memory for verbs and colors of objects was assessed, with object names serving as cues. In Experiment 2, object and color memory were assessed, with verbs serving as cues. Results from both experiments indicated a greater deterioration of memory performance under divided attention for verbal features than for colors. In addition, intention to remember did not affect performance for any feature in either experiment. The overall pattern of outcome is discussed relative to the view that encoding of verbal features of SPTs is more attention‐demanding than encoding of physical task features, such as color.
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| 34. |
- Bäckman, Lars, et al.
(författare)
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Effects of working-memory training on striatal dopamine release
- 2011
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 333:6043, s. 718-
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Tidskriftsartikel (refereegranskat)abstract
- Updating of working memory has been associated with striato-frontal brain regions and phasic dopaminergic neurotransmission. We assessed raclopride binding to striatal dopamine (DA) D2 receptors during a letter-updating task and a control condition before and after 5 weeks of updating training. Results showed that updating affected DA activity before training and that training further increased striatal DA release during updating. These findings highlight the pivotal role of transient neural processes associated with D2 receptor activity in working memory.
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| 35. |
- Bäckman, Lars, et al.
(författare)
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Increased dopamine release after working-memory updating training : Neurochemical correlates of transfer
- 2017
-
Ingår i: Scientific Reports. - : NATURE PUBLISHING GROUP. - 2045-2322. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Previous work demonstrates that working-memory (WM) updating training results in improved performance on a letter-memory criterion task, transfers to an untrained n-back task, and increases striatal dopamine (DA) activity during the criterion task. Here, we sought to replicate and extend these findings by also examining neurochemical correlates of transfer. Four positron emission tomography (PET) scans using the radioligand raclopride were performed. Two of these assessed DAD2 binding (letter memory; n-back) before 5 weeks of updating training, and the same two scans were performed post training. Key findings were (a) pronounced training-related behavioral gains in the lettermemory criterion task, (b) altered striatal DAD2 binding potential after training during letter-memory performance, suggesting training-induced increases in DA release, and (c) increased striatal DA activity also during the n-back transfer task after the intervention, but no concomitant behavioral transfer. The fact that the training-related DA alterations during the transfer task were not accompanied by behavioral transfer suggests that increased DA release may be a necessary, but not sufficient, condition for behavioral transfer to occur.
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| 36. |
- Bäckman, Lars, et al.
(författare)
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Linking cognitive aging to alterations in dopamine neurotransmitter functioning : Recent data and future avenues
- 2010
-
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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| 37. |
- Dahlin, Erika, 1981-, et al.
(författare)
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Plasticity of executive functioning in young and older adults : immediative training gains, transfer, and long-term maintenance
- 2008
-
Ingår i: Psychology and Aging. - : American Psychological Association. - 0882-7974 .- 1939-1498. ; 23:4, s. 720-730
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Tidskriftsartikel (refereegranskat)abstract
- The authors investigated immediate training gains, transfer effects, and 18-month maintenance after 5 weeks of computer-based training in updating of information in working memory in young and older subjects. Trained young and older adults improved significantly more than controls on the criterion task (letter memory), and these gains were maintained 18 months later. Transfer effects were in general limited and restricted to the young participants, who showed transfer to an untrained task that required updating (3-back). The findings demonstrate substantial and durable plasticity of executive functioning across adulthood and old age, although there appear to be age-related constraints in the ability to generalize the acquired updating skill.
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| 38. |
- Dahlin, Erika, 1981-, et al.
(författare)
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Training of the executive component of working memory : subcortial areas mediate transfer effects
- 2009
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Ingår i: Restorative Neurology and Neuroscience. - : IOS Press. - 0922-6028 .- 1878-3627. ; 27:5, s. 405-419
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Several recent studies show that training can improve working memory (WM) performance. In this review, many issues related to WM training, such as neural basis, transfer effects, and age-related changes are addressed. Method: We focus on our own studies investigating training on tasks taxing the executive updating function and discuss our findings in relation to results from other studies investigating training of the executive component of WM. Results: The review confirms positive behavioral effects of training on working memory. The most common neural pattern following training is fronto-parietal activity decreases. Increases in sub-cortical areas are also frequently reported after training, and we suggest that such increases indicate changes in the underlying skill following training. Transfer effects are in general difficult to demonstrate. Some studies show that older adults increase their performance after WM training. However, transfer effects are small or nonexistent in old age. Conclusions: The main finding in this review is that sub-cortical areas seem to have a critical role in mediating transfer effects to untrained tasks after at least some forms of working memory training (such as updating).
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| 39. |
- Dahlin, Erika, 1981-, et al.
(författare)
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Transfer of learning after updating training mediated by the striatum
- 2008
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 320:5882, s. 1510-1512
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Tidskriftsartikel (refereegranskat)abstract
- Process-specific training can improve performance on untrained tasks, but the magnitude of gain is variable and often there is no transfer at all. We demonstrate transfer to a 3-back test of working memory after 5 weeks of training in updating. The transfer effect was based on a joint training-related activity increase for the criterion (letter memory) and transfer tasks in a striatal region that also was recruited pretraining. No transfer was observed to a task that did not engage updating and striatal regions, and age-related striatal changes imposed constraints on transfer. These findings indicate that transfer can occur if the criterion and transfer tasks engage specific overlapping processing components and brain regions.
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| 40. |
- de Boer, Lieke, et al.
(författare)
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Corticostriatal White Matter Integrity and Dopamine D1 Receptor Availability Predict Age Differences in Prefrontal Value Signaling during Reward Learning
- 2020
-
Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:10, s. 5270-5280
-
Tidskriftsartikel (refereegranskat)abstract
- Probabilistic reward learning reflects the ability to adapt choices based on probabilistic feedback. The dopaminergically innervated corticostriatal circuit in the brain plays an important role in supporting successful probabilistic reward learning. Several components of the corticostriatal circuit deteriorate with age, as it does probabilistic reward learning. We showed previously that D1 receptor availability in NAcc predicts the strength of anticipatory value signaling in vmPFC, a neural correlate of probabilistic learning that is attenuated in older participants and predicts probabilistic reward learning performance. We investigated how white matter integrity in the pathway between nucleus accumbens (NAcc) and ventromedial prefrontal cortex (vmPFC) relates to the strength of anticipatory value signaling in vmPFC in younger and older participants. We found that in a sample of 22 old and 23 young participants, fractional anisotropy in the pathway between NAcc and vmPFC predicted the strength of value signaling in vmPFC independently from D1 receptor availability in NAcc. These findings provide tentative evidence that integrity in the dopaminergic and white matter pathways of corticostriatal circuitry supports the expression of value signaling in vmPFC which supports reward learning, however, the limited sample size calls for independent replication. These and future findings could add to the improved understanding of how corticostriatal integrity contributes to reward learning ability.
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| 41. |
- Fischer, Håkan, et al.
(författare)
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Age-related differences in brain regions supporting successful encoding of emotional faces.
- 2010
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Ingår i: Cortex. - Milano : Elsevier BV. - 0010-9452 .- 1973-8102. ; 46:4, s. 490-497
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Tidskriftsartikel (refereegranskat)abstract
- In an event-related functional Magnetic Resonance Imaging (fMRI) study, younger and older adults were presented with negative emotional (i.e., fearful) and neutral face pictures under incidental learning conditions. They were subsequently given a test of face recognition outside the scanner. Both age groups activated amygdala bilaterally as well as the right hippocampus during successful encoding of the fearful faces. Direct age comparisons revealed greater activation in right amygdala and bilateral hippocampus in the young, whereas older adults showed greater activation in the left insular and right prefrontal cortices. None of these brain areas was activated during successful encoding of neutral faces, suggesting specificity of these brain activation patterns. The results indicate an age-related shift in the neural underpinnings of negative emotional face processing from medial-temporal to neocortical regions.
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| 42. |
- Fischer, Håkan, et al.
(författare)
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Brain activation while forming memories of fearful and neutral faces in women and men
- 2007
-
Ingår i: Emotion. - : American Psychological Association (APA). - 1528-3542 .- 1931-1516. ; 7:4, s. 767-773
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Event-related functional MRI (fMRI) was used to assess brain activity during encoding of fearful and neutral faces in 12 women and 12 men. In a subsequent memory analysis, the authors separated successful from unsuccessful encoding of both types of faces, based on whether they were remembered or forgotten in a later recognition memory test. Overall, women and men recruited overlapping neural circuitries. Both sexes activated right-sided medial-temporal regions during successful encoding of fearful faces. Successful encoding of neutral faces was associated with left-sided lateral prefrontal and right-sided superior frontal activation in both sexes. In women, relatively greater encoding related activity for neutral faces was seen in the superior parietal and parahippocampal cortices. By contrast, men activated the left and right superior/middle frontal cortex more than women during successful encoding of the same neutral faces. These findings suggest that women and men use similar neural networks to encode facial information, with only subtle sex differences observed for neutral faces.
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| 43. |
- Garzón, Benjamín, et al.
(författare)
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Investigating associations of delay discounting with brain structure, working memory, and episodic memory
- 2022
-
Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199.
-
Tidskriftsartikel (refereegranskat)abstract
- Introduction: Delay discounting (DD), the preference for smaller and sooner rewards over larger and later ones, is an important behavioural phenomenon for daily functioning of increasing interest within psychopathology. The neurobiological mechanisms behind DD are not well understood and the literature on structural correlates of DD shows inconsistencies.Methods: Here we leveraged a large openly available dataset (n = 1196) to investigate associations with memory performance and gray and white matter correlates of DD using linked independent component analysis.Results: Greater DD was related to smaller anterior temporal gray matter volume. Associations of DD with total cortical volume, subcortical volumes, markers of white matter microscopic organization, working memory, and episodic memory scores were not significant after controlling for education and income.Conclusion: Effects of size comparable to the one we identified would be unlikely to be replicated with sample sizes common in many previous studies in this domain, which may explain the incongruities in the literature. The paucity and small size of the effects detected in our data underscore the importance of using large samples together with methods that accommodate their statistical structure and appropriate control for confounders, as well as the need to devise paradigms with improved task parameter reliability in studies relating brain structure and cognitive abilities with DD.
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| 44. |
- Garzón, Benjamín, et al.
(författare)
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Role of dopamine and gray matter density in aging effects and individual differences of functional connectomes
- 2021
-
Ingår i: Brain Structure and Function. - : Springer Science and Business Media LLC. - 1863-2653 .- 1863-2661. ; 226, s. 743-758
-
Tidskriftsartikel (refereegranskat)abstract
- With increasing age, functional connectomes become dissimilar across normal individuals, reflecting heterogenous aging effects on functional connectivity (FC). We investigated the distribution of these effects across the connectome and their relationship with age-related differences in dopamine (DA) D1 receptor availability and gray matter density (GMD). With this aim, we determined aging effects on mean and interindividual variance of FC using fMRI in 30 younger and 30 older healthy subjects and mapped the contribution of each connection to the patterns of age-related similarity loss. Aging effects on mean FC accounted mainly for the dissimilarity between connectomes of younger and older adults, and were related, across brain regions, to aging effects on DA D1 receptor availability. Aging effects on the variance of FC indicated a global increase in variance with advancing age, explained connectome dissimilarity among older subjects and were related to aging effects on variance of GMD. The relationship between aging and the similarity of connectomes can thus be partly explained by age differences in DA modulation and gray matter structure.
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| 45. |
- 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
-
Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 29:2, s. 384-392
-
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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| 46. |
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| 47. |
- Gustafsson, Bengt I., 1955, et al.
(författare)
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Retransplantation of the liver.
- 2006
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Ingår i: Transplantation proceedings. - : Elsevier BV. - 0041-1345. ; 38:5, s. 1438-9
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Tidskriftsartikel (refereegranskat)abstract
- Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction. The outcome of a second procedure depends upon several factors, some of which are not defined at the time of the decision to retransplant. This study is an analysis of all re-TX of the liver performed at our unit between January 1995 and January 2004. Among the 474 liver TX were 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation, peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graft survivals. Patients who underwent re-TX did not differ from those transplanted once with regard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliary tract complications/chronic rejection, one-third hepatic artery thrombosis, and one-third others, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and "elective" in 26 cases. Complications were common; about half of the patients were reoperated due to bleeding or biliary problems. To date (May 2004), 15 patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning grafts. In summary, liver re-TX is a complicated procedure associated with significant mortality and morbidity, but considering that the actual patient group has a poor prognosis without re-TX, the results are nevertheless encouraging.
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| 48. |
- Hellström, Vivan, et al.
(författare)
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Malignancies in transplanted patients : Multidisciplinary evaluation and switch to mTOR inhibitors after kidney transplantation - experiences from a prospective, clinical, observational study
- 2016
-
Ingår i: Acta Oncologica. - Uppsala : Acta Universitatis Upsaliensis. - 0284-186X .- 1651-226X. ; 55:6, s. 774-781
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Tidskriftsartikel (refereegranskat)abstract
- Background Solid organ transplant recipients are at increased risk of developing malignancies. The objective of this prospective, observational, one-armed study was to study the feasibility to add a mammalian target of rapamycin (mTOR) inhibitor to the immunosuppressive regimen in transplanted patients with post-transplant malignancies. During the trial the need to improve identification of post-transplant malignancies and to reassure adequate oncological treatment of these patients became evident. Multidisciplinary team (MDT) evaluation of oncological and immunosuppressive treatments was implemented for all patients with malignancies after renal or combined renal and pancreas transplantation because of the trial.Material and methods At Uppsala University Hospital, Sweden, a MDT consisting of transplant surgeons, nephrologists, oncologists and dermatologists evaluated 120 renal or combined renal and pancreas-transplanted recipients diagnosed with malignancies from September 2006 to July 2012. To identify all malignancies, the population was linked to the Regional Tumor Registry (RTR). We recorded to which extent a switch to mTOR inhibitors was possible and how often the originally planned oncological managements were adjusted. All patients were followed for three years. (ClinicalTrials.gov: NCT02241564).Results In 76 of 120 patients (63%) a switch to mTOR inhibitors was possible. Immunosuppression was interrupted in seven patients (6%), reduced in three patients (2%) and remained unchanged in 34 of 120 patients (28%). Identification of post-transplant malignancies increased significantly after linkage to RTR (p=0.015). The initially recommended oncological treatment was adjusted in 23 of 44 patients (52%) with solid or hematological malignancies; 36 of these patients (82%) were treated according to national guidelines.Conclusion In two thirds of the patients the immunosuppressive treatment could be changed to an mTOR inhibitor with anti-tumor effects in transplanted patients with post-transplant malignancies. The use of regional tumor registers considerably improved the identification of patients with post-transplant malignancies indicating that post-transplant malignancies might be timely underreported in transplant registers.
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| 49. |
- Johansson, Jarkko, et al.
(författare)
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Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan
- 2023
-
Ingår i: Cell Reports. - 2211-1247. ; 42:9
-
Tidskriftsartikel (refereegranskat)abstract
- Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of in vivo assessments (n = 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.
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| 50. |
- Jones, Sari, et al.
(författare)
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Cognitive and neural plasticity in aging : general and task-specific limitations.
- 2006
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Ingår i: Neuroscience Biobehavioral Reviews. - : Elsevier BV. - 0149-7634. ; 30:6, s. 864-71
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- There is evidence for cognitive as well as neural plasticity across the adult life span, although aging is associated with certain constraints on plasticity. In the current paper, we argue that the age-related reduction in cognitive plasticity may be due to (a) deficits in general processing resources, and (b) failure to engage in task-relevant cognitive operations. Memory-training research suggests that age-related processing deficits (e.g., executive functions, speed) hinder older adults from utilizing mnemonic techniques as efficiently as the young, and that this age difference is reflected by diminished frontal activity during mnemonic use. Additional constraints on memory plasticity in old age are related to difficulties that are specific to the task, such as creating visual images, as well as in binding together the information to be remembered. These deficiencies are paralleled by reduced activity in occipito-parietal and medial-temporal regions, respectively. Future attempts to optimize intervention-related gains in old age should consider targeting both general processing and task-specific origins of age-associated reductions in cognitive plasticity.
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