The role of dopamine in human cognition

Our research addresses the general hypothesis that decline in dopamine functions with old age explain aging-related declines in learning memory. We are involved in the design, data collection and analyses of several human positron emission tomography (PET) studies of the aging human dopamine system. Our efforts to combine PET with cognitive testing and MRI in the same sample of older adults were among the first studies of this kind in the world. These early findings and subsequent data collections by other groups have led to dopamine function being a widely recognized and important marker of brain and cognitive aging.

 

Example publications:

  • Grill, F., Guitart-Masip, M., Johansson, J., Stiernman, L., Axelsson, J., Nyberg, L., Rieckmann, A. (2024). Dopamine release in human associative striatum during reversal learning. Nature Communications, 15, 59.
  • Pedersen R, Johansson J, Nordin K, Rieckmann A, Wåhlin A, Nyberg L, Bäckman L, Salami A. (2024). Dopamine D1-Receptor Organization Contributes to Functional Brain Architecture. J Neurosci, 44:e0621232024.
  • Johansson J, Nordin K, Pedersen R, Karalija N, Papenberg G, Andersson M, Korkki SM, Riklund K, Guitart-Masip M, Rieckmann A, Bäckman L, Nyberg L, Salami A. (2023). Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan. Cell Reports, 42, 113107.
  • Rieckmann, A., Johnson, K.A., Sperling R.A., Buckner, R.L., Hedden, T. (2018). Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging. PNAS, 115, 10160-10165.
  • Rieckmann, A., Hedden, T., Younger, A.P., Sperling, R.A.., Johnson, K.A., Buckner, RL. (2015). Dopamine transporter availability in clinically normal aging is associated with individual differences in white matter integrity. Human Brain Mapp, 37, 621-631.

 

Imaging biomarkers of cognitive impairment in neurodegenerative diseases

In parallel to our interest in neurotransmitter changes during “normal” cognitive aging, we want to understand the accumulation of pathological age-related changes in the context of the neurodegenerative diseases Parkinson’s disease and Alzheimer’s disease. In addition to own imaging data collections, we use existing data from large-scale patient populations such as ADNI and PPMI. MRI-based markers of disease supplement and enrich our understanding of neurodegeneration.

 

Example publications:

  • Andersson, S., Josefsson, M., Stiernman, L.J., Rieckmann, A. (2021). Cognitive decline in Parkinson’s disease: a subgroup of extreme decliners revealed by a data-driven analysis of longitudinal progression. Frontiers in Psychology, 2, 729755.
  • Wachinger, C., Nho, K., Saykin, A., Reuter, M., Rieckmann, A. (2018): A Longitudinal Imaging Genetics Study of Neuroanatomical Asymmetry in Alzheimer’s Disease, BiolPsychiatry.84, 522-530 [commentary by Parker and Schott, Navigating genetic influences on the topography of Alzheimer’s disease. Biological Psychiatry 2018, 84:476-477.]
  • Rieckmann, A., Van Dijk., K.V.D., Sperling, R.A., Johnson, K.A., Buckner, R.L., Hedden, T. (2016): Accelerated decline in white matter integrity in clinically normal individuals at risk for Alzheimer’s disease. Neurobiol Aging. 42, 177-188.
  • Rieckmann, A., Gomperts, S.N., Johnson, K.A., Growdon, J.H., Van Dijk, K.R.A (2015): Putamen–midbrain functional connectivity is related to striatal dopamine transporter availability in patients with Lewy body diseases. NeuroImage Clin, 8, 554-559.

 

Novel multi-modal imaging approaches

To better understand what MRI can and cannot tell us about brain and cognitive aging, we develop and use novel hybrid imaging approaches in which functional MRI and functional, dynamic PET images are acquired on a hybrid scanner while a person is engaged in a cognitive task. In one of our most recently completed studies, we found no support for the long-held assumption of functional brain compensation in well-performing older adults. Rather, we, along with others in the field, emphasize that maintained cognition in older adults likely reflects maintained brain health, rather than a re-wiring of connections. It is imperative to build on this research to better understand the factors across the lifespan that determine cognitive reserve and maintained brain health and cognition in old age.

 

Example publications:

  • Stiernman, J.L., Grill, F., McNulty, C., Bahrd, P., Panes Lundmark, V., Axelsson, J., Salami, A., Rieckmann, A.(2023). Widespread fMRI BOLD signal overactivations during cognitive control in older adults are not matched by corresponding increases in fPET glucose metabolism. The Journal of Neuroscience, 5, 2527-2536.
  • Stiernman J.L., Grill, F., Hahn, A., Rischka, L., Lanzenberger, R., Lundmark, V.P., Riklund, K., Axelsson, J., Rieckmann, A. (2021). Dissociations between glucose metabolism and blood oxygenation in the human default mode network revealed by simultaneous pet-fmri. PNAS, 118(27) e2021913118. [commentary by Goyal, M.S., and Synder, A. Z. (2021). Uncoupling in intrinsic brain activity. PNAS, 118(34) e2110556118.
  • Grill, F., Johansson, J., Axelsson, J., Brynolfsson, P., Nyberg, L., & Rieckmann, A. (2021). Dissecting Motor and Cognitive Component Processes of a Finger-Tapping Task With Hybrid Dopamine Positron Emission Tomography and Functional Magnetic Resonance Imaging. Frontiers in human neuroscience,15, https://doi.org/10.3389/fnhum.2021.733091.

 

ERC Project: Aging-related changes in brain activation and deactivation during cognition

 

Utilizing the survey setting to understand risk factors for cognitive aging

The substantial individual and societal burdens of cognitive decline in aging underscore the need to also develop and monitor risk factors in settings without laboratory infrastructure or brain imaging capabilities. In 2015, the SHARE survey expanded its interview-based data collection by including dried blood spots to analyze health biomarkers. Our specific research in SHARE focuses on associations between dementia risk factors from dried blood spots and cognitive performance. We have identified circulating apoE4 levels as a potential intervention target for individuals with a genetic risk for Alzheimer’s disease. Together, our work in SHARE underscores the importance of developing tailored interventions and policies that address an individual’s unique bio-psycho-social risk profile.