| 1. |
- Bäckman, Lars, et al.
(författare)
-
Dopamine D(1) receptors and age differences in brain activation during working memory
- 2011
-
Ingår i: Neurobiology of Aging. - Fayetteville, N.Y : Elsevier. - 0197-4580 .- 1558-1497. ; 32:10, s. 1849-1856
-
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.
|
|
| 2. |
|
|
| 3. |
- Karlsson, Sari, et al.
(författare)
-
Modulation of striatal dopamine D1 binding by cognitive processing
- 2009
-
Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 48:2, s. 398-404
-
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.
|
|
| 4. |
- Karlsson, Sari, et al.
(författare)
-
Relationship of dopamine D1 receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans
- 2011
-
Ingår i: NeuroImage. - : Elsevier. - 1053-8119 .- 1095-9572. ; 57:2, s. 346-351
-
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.
|
|
| 5. |
- Rieckmann, Anna, et al.
(författare)
-
Dopamine D1 Receptor Associations within and between Dopaminergic Pathways in Younger and Elderly Adults : Links to Cognitive Performance
- 2011
-
Ingår i: Cerebral Cortex. - Oxford : Oxford University Press. - 1047-3211 .- 1460-2199. ; 21:9, s. 2023-2032
-
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.
|
|
| 6. |
- MacDonald, Stuart WS, et al.
(författare)
-
Aging-related increases in behavioral variability : relations to losses of dopamine D-1 receptors
- 2012
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:24, s. 8186-8191
-
Tidskriftsartikel (refereegranskat)abstract
- Intraindividual variability (IIV) reflects within-person changes in performance, such as trial-by-trial fluctuations on a reaction-time (RT) task. The neural underpinnings of IIV remain largely unknown. The neurotransmitter dopamine (DA) is of particular interest here, as human populations that exhibit DA alterations, such as the elderly, attention deficit hyperactivity disorder children, persons with schizophrenia, and Parkinson patients, also show increased behavioral IIV. We examined links between DA D-1 binding potential (BP) in multiple brain regions and IIV for the control and interference conditions of the Multi-Source Interference Task (MSIT), tapping the cingulo-fronto-parietal attention network. Participants were 18 young and 20 healthy old adults. PET and the radioligand [C-11]SCH23390 were used to determine D-1 BP. The intraindividual standard deviation (ISD) was computed across successful latency trials of the MSIT conditions, independent of mean RT differences due to age, trial, and condition. Increasing ISDs were associated with increasing age and diminished D-1 binding in several brain regions (anterior cingulate gyrus, dorsolateral prefrontal cortex, and parietal cortex) for the interference, but not control, condition. Analyses of partial associations indicate that the association between age and IIV in the interference condition was linked to D-1 receptor losses in task-relevant brain regions. These findings suggest that dysfunctional DA modulation may contribute to increased variability in cognitive performance among older adults.
|
|
| 7. |
- Laukka, Erika J., et al.
(författare)
-
Genetic Effects on Old-Age Cognitive Functioning : A Population-Based Study
- 2013
-
Ingår i: Psychology and Aging. - : American Psychological Association (APA). - 0882-7974 .- 1939-1498. ; 28:1, s. 262-274
-
Tidskriftsartikel (refereegranskat)abstract
- Associations between genotypes and cognitive outcomes may provide clues as to which mechanisms cause individual differences in old-age cognitive performance. We investigated the effects of five polymorphisms on cognitive functioning in a population-based sample of 2,694 persons without dementia (60-102 years). A structural equation model (SEM) was fit to the cognitive data, yielding five specific latent factors (perceptual speed, episodic memory, semantic memory, category fluency, and letter fluency), as well as a global cognitive factor. These factors showed the expected associations with chronological age. Genotyping was performed for five single-nucleotide polymorphisms that have been associated with cognitive performance: APOE (rs429358), COMT (rs4680), BDNF (rs6265), KIBRA (rs17070145), and CLSTN2 (rs6439886). After controlling for age, gender, and education, as well as correcting for multiple comparisons, we observed negative effects of being an APOE ε4 carrier on episodic memory and perceptual speed. Furthermore, being a CLSTN2 TT carrier was associated with poorer semantic memory. For the global factor, the same pattern of results was observed. In addition, being a BDNF any A carrier was associated with better cognitive performance. Also, older age was associated with stronger genetic effects of APOE on global cognition. However, this interaction effect was partly driven by the presence of preclinical dementia cases in our sample. Similarly, excluding future dementia cases attenuated the effects of APOE on episodic memory and global cognition, suggesting that part of the effects of APOE on old-age cognitive performance may be driven by dementia-related processes.
|
|
| 8. |
- MacDonald, Stuart W S, et al.
(författare)
-
Trajectories of cognitive decline following dementia onset : what accounts for variation in progression?
- 2011
-
Ingår i: Dementia and Geriatric Cognitive Disorders. - Basel : Karger. - 1420-8008 .- 1421-9824. ; 31:3, s. 202-209
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Delineating the natural history of dementia progression has important clinical implications, including reducing caregiver burden and targeting effective drug trials. We examined whether trajectories of cognitive change differed reliably after diagnosis, and whether diverse predictors of such differences (demographic, psychological, biological, genetic, social) could be identified.METHODS: Cognitive change was examined for incident dementia cases (mild: n = 156; moderate: n = 77; severe: n = 73) and controls (n = 249) from the Kungsholmen Project, a community-based study of adults 75 years and older.RESULTS: For those with dementia, total variance attributed to between-person differences in cognitive decline was modest and linked to but a single predictor (history of cardiovascular disease). Although less variance in cognitive decline was observed for the similarly aged controls, numerous significant predictors of these differences were identified.CONCLUSION: The neurodegenerative process underlying dementia overshadows formerly significant predictors of cognitive change.
|
|
| 9. |
- Rieckmann, Anna, et al.
(författare)
-
Caudate Dopamine D1 Receptor Density Is Associated with Individual Differences in Frontoparietal Connectivity during Working Memory
- 2011
-
Ingår i: Journal of Neuroscience. - : Society for Neuroscience. - 0270-6474 .- 1529-2401. ; 31:40, s. 14284-14290
-
Tidskriftsartikel (refereegranskat)abstract
- We assess the relationship of age-related losses in striatal D1 receptor densities to age-related reductions in functional connectivity between spatially distinct cortical regions in healthy human participants. Previous neuroimaging studies have reported age-related differences in functional connectivity of the frontoparietal working memory network and the default mode network during task performance. We used functional magnetic resonance imaging and seed-based connectivity (right dorsolateral and medial prefrontal cortex) to extend these findings: Anterior-posterior connectivity of both these functional networks was reduced in older (65-75 years, n = 18) compared with younger (20-30 years, n = 19) adults, whereas bilateral connectivity in prefrontal cortex was increased in older adults. Positron emission tomography with the D1 receptor ligand [(11)C]SCH23390 was used to assess caudate D1 receptor density in the same sample. Older adults showed significantly reduced caudate D1 receptor density compared to the younger adults. Of key interest, partial correlations showed that individual differences in caudate D1 receptor density were positively associated with individual differences in dorsolateral prefrontal connectivity to right parietal cortex (BA40) and negatively with medial prefrontal connectivity to right parietal cortex (BA40 and postcentral gyrus), after controlling for age. We found no correlation of caudate D1 receptor density with anterior-posterior coupling within the default mode network or with bilateral frontal connectivity. These results are consistent with animal work that has identified a role for caudate D1 receptors in mediating information transfer between prefrontal areas and parietal cortex.
|
|
| 10. |
- Rieckmann, Anna, et al.
(författare)
-
Increased Bilateral Frontal Connectivity during Working Memory in Young Adults under the Influence of a Dopamine D1 Receptor Antagonist
- 2012
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 32:48, s. 17067-17072
-
Tidskriftsartikel (refereegranskat)abstract
- Increased frontal bilaterality in old compared with young adults during cognitive performance is a common finding in human functional neuroimaging studies. Age-related reductions in laterality are a widely debated topic and their origins and consequences may be manifold. The current study demonstrates that a dopamine (DA) D1 antagonist induces increased frontal bilateral connectivity in healthy young adults revealed by functional magnetic resonance imaging during a spatial working memory task. Moreover, increases in functional connectivity between right and left prefrontal cortex during the pharmacological challenge were associated with maintaining performance on drug. To our knowledge, this is the first study to pharmacologically induce increased frontal bilateral functional connectivity during a cognitive task in young adults and to show that increased bilaterality is associated with less severe cognitive impairment under the influence of a DA receptor antagonist.
|
|
