Dopamine functions and cognitive aging

In multimodal imaging work with young and old adults, we use both PET and fMRI to determine relationships between DA activity and functional brain activity during working memory performance. Results show that age-related losses of D1 receptors in caudate and frontal cortex contribute to under-recruitment of task-relevant fronto-parietal regions and working-memory deficits in old age¹. Further, D1 receptor losses in aging are related to reduced fronto-parietal connectivity and increased fronto-frontal connectivity². In another study, young adults were given a dopaminergic antagonist that blocks approximately 50% of D1 receptors in caudate and frontal cortex. Under the influence of the antagonist, the young showed reduced fronto-parietal connectivity and increased fronto-frontal connectivity along with impaired working-memory performance, thereby mimicking the patterns seen among old adults under normal conditions³.

Other research indicates that the brain DA systems may be segregated in aging. Whereas young adults showed high intercorrelations in D1 binding within and between regions in the nigrostriatal, mesolimbic, and mesocortical pathways, old adults exhibited strong within-pathway links, but markedly reduced relationships in D1 binding of nigrostriatal to mesolimbic and mesocortical pathways. Importantly, weak between-pathway correlations in old adults were found only for the slower half of the sample, as measured with a cognitive interference task. These results suggest that D1 receptor densities in different pathways are not regulated independently in younger adults, but segregate in old age, and that this segregation of D1 receptor systems may be related to age-related cognitive slowing⁴.

Moreover, intra-individual variability (IIV) in speed of responding in reaction-time tasks has been associated with various conditions characterized by altered DA neurotransmission (e.g., Parkinson’s disease, schizophrenia, and ADHD). In one study, we obtained direct evidence of a DA-IIV link⁵. Here, old adults exhibited reduced D1 binding in various cortical regions that was linked to increased IIV during an interference resolution task. The DA-cognition relationship may also be observed irrespective of age. In an age-homogenous sample of young adults, we observed strong associations between D1 markers in striatum and hippocampus and performance on tasks assessing knowledge, speed, and executive functioning⁶.

Finally, we have documented novel evidence for DA release after training in updating information in working memory⁷. This research, along with other intervention work on working memory, was summarized in a recent review⁸.

1. Bäckman L, Karlsson S, Fischer H, Karlsson P, Brehmer Y, Rieckmann A, MacDonald SW, Farde L, Nyberg, L.  Dopamine D₁ receptors and age differences in brain activation during working memory. Neurobiol Aging 2011; 32(10):1849-1856.
2. Rieckmann A, Karlsson S, Fischer H, Bäckman L. Caudate dopamine D1 receptor density is associated with individual differences in frontoparietal connectivity during working memory. J Neurosci 2011; 31(40):14284-14290.
3. Rieckmann A, Karlsson S, Fischer H, Bäckman L. Increased bilateral frontal connectivity during working memory in young adults under the influence of a dopamine D1 receptor antagonist. J Neurosci 2012; 28:17067-17072.
4. Rieckmann A, Karlsson S, Karlsson P, Brehmer Y, Fischer H, Farde L, et al. Dopamine D1 receptor associations within and between dopaminergic pathways in younger and elderly adults: links to cognitive performance. Cereb Cortex 2011; 21(9):2023-2032.
5. MacDonald SW, Karlsson S, Rieckmann A, Nyberg L, Bäckman L. Aging-related increases in behavioral variability: relations to losses of dopamine D1 receptors. J Neurosci 2012; 32(24):8186-8191.
6. Karlsson S, Rieckmann A, Karlsson P, Farde L, Nyberg L, Bäckman L. Relationship of dopamine D₁ receptor binding in striatal and extrastriatal regions to cognitive functioning in healthy humans. Neuroimage 2011; 57:346-351.
7. Bäckman L, Nyberg L, Soveri A, Johansson J, Andersson M, Dahlin E, et al. Effects of working-memory training on striatal dopamine release. Science 2011; 333(6043):718.
8. Bäckman L, Nyberg L. Dopamine and training-related working-memory improvement. Neurosci Biobehav Rev [In press: online] 2013. Available from: http://dx.doi.org/10.1016/j.neubiorev.2013.01.014.