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Cognition, brain, and aging (COBRA): A longitudinal multimodal imaging study

Memory functions and other cognitive abilities (such as attention and executive functions) decline for many elderly persons. Globally, major efforts are taken to investigate if this kind of decline can be reduced, for example through systematic training. These actions, if they are successful, could be of great importance for both individuals and society in general. However, there is still missing a lot of knowledge concerning how cognitive decline is connected to age-related changes in the brain.

In particular, there are very few longitudinal studies in which individuals are followed over time that maps changes in the brain in relation to changes in cognitive abilities. This is a critical shortage since the existing results, for example from the Swedish Betula-project, clearly shows that longitudinal data can strongly deviate from attempts to estimate age-related changes from cross-sectional studies (that are comparing individuals of different ages).

The purpose with this project is that for a decade to follow, and on three occasions examine a group of about 190 people between 63 and 67 years of age. The study's design and the thorough measurements have been developed to maximize the chances of capturing subtle patterns of change over time, and the participating researchers specific expertise ensures that the study is carried out in an optimal way. Participants undergo a thorough cognitive examination, brain structure and functional activation patterns are examined with MRI and functionality of the brain's dopamine system is mapped with positron emission tomography (PET). The latter is a unique contribution to the international research community and is highly topical because different studies show that dopamine function is not only critical for our motor skills, but also cognition.

We expect that some of the participants will demonstrate impaired cognitive ability, which can be related to the different brain recordings. In addition, lifestyle habits will be identified, such as physical activity, diet and sleep, which can further illustrate why deterioration is seen in some but not other individuals. Such knowledge can inform theory and practice about the aging brain's constraints and opportunities.


Cognitive impairments in aging compromise the well-being of individuals and make independent living difficult. Such impairments come with major individual and societal costs. Hence, developing means of preserving functioning in old age is of great importance. However, current knowledge of the brain mechanisms underlying age-related cognitive decline is insufficient to inform design of effective intervention programs. Few studies have comprehensively integrated age-related brain changes as measured by different in vivo imaging modalities and linked such changes to cognitive decline, and hardly any previous multi-modal imaging studies used a longitudinal design. This is a noteworthy omission as inferences of change from cross-sectional comparisons may significantly deviate from inferences based on actually measured longitudinal change.

We will follow a large representative cohort of 63-67 year-old healthy individuals over one decade, and at multiple measurement points assess dopamine availability, structural integrity of white and grey matter, functional brain integrity, cognitive performance, and engagement in relevant life-style activities. Thereby, we will yield crucial and novel information on brain mechanisms of cognitive decline in aging as well as on how life-style choices may induce protective effects on brain functions and related cognitive operations. This information will pave the road for successful design and implementation of intervention and prevention programs.


The study will follow a large cohort (n = 190) of 63-67 year-old healthy individuals randomly selected from the population registry in Umeå over a 10 year period. Cognitive performance, functional and structural brain integrity, and relevant lifestyle-related factors will be assessed at three measurement points, each separated by 4.5 years.


Principal Investigator

Lars Nyberg (Umeå Universitet)


Katrine Riklund (Umeå Universitet)

Lars Bäckman (Karolinska Institutet)

Ulman Lindeberger (Max Planck Institute for Human Development, Berlin)

Martin Lövdén (Karolinska Institutet)


Jan Axelsson (PET- physicist)

Kajsa Burström (research nurse)

Rebeca de Peredo Axelsson (research nurse)

Nils Rittfeldt (research nurse)

Mikael Stiernstedt (lab coordinator)

Margareta Ögren (PET-chemists)

Mats Ögren (PET-chemists)

Involved UFBI members

Lars Nyberg

Katrine Riklund

Nina Karalija

Involved partners

Lars Bäckman (Karolinska Institutet, Stockholm)

Matrin Lövdén (Karolinska Institutet, Stockholm)

Ulman Lindenberger (Max Planck Institute for Human Development, Berlin)




de Boer, L., Garzón, B., Axelsson J., Riklund, K., Nyberg, L., Bäckman, L. & Guitart-Masip, M. (accepted). Corticostriatal white matter integrity and dopamine D1 receptor availability independently predict age differences in prefrontal value signaling during reward learning. Cerebral Cortex.



de Boer, L., Garzón, B., Axelsson J., Riklund, K., Nyberg, L., Bäckman, L. & Guitart-Masip, M. (2020). Corticostriatal white matter integrity and dopamine D1 receptor availability independently predict age differences in prefrontal value signaling during reward learning. Cerebral Cortex.

Papenberg, G., Karalija, N., Salami, A., Andersson, M., Axelsson, J., Riklund, K., … Bäckman, L. (2019). The Influence of Hippocampal Dopamine D2 Receptors on Episodic Memory Is Modulated by BDNF and KIBRA Polymorphisms. Journal of Cognitive Neuroscience, 31(9), 1422–1429.

Karalija, N., Wåhlin, A., Ek, J., Rieckmann, A., Papenberg, G., Salami, A., … Nyberg, L. (2019). Cardiovascular factors are related to dopamine integrity and cognition in aging. Annals of Clinical and Translational Neurology, 6(11), 2291–2303.

Papenberg, G., Jonasson, L., Karalija, N., Johansson, J., Köhncke, Y., Salami, A., … Bäckman, L. (2019). Mapping the landscape of human dopamine D2/3 receptors with [11C]raclopride. Brain Structure and Function.

Papenberg, G., Karalija, N., Salami, A., Rieckmann, A., Andersson, M., Axelsson, J., … Bäckman, L. (2019). Balance between Transmitter Availability and Dopamine D2 Receptors in Prefrontal Cortex Influences Memory Functioning. Cerebral Cortex.

Salami, A., Garrett, D. D., Wåhlin, A., Rieckmann, A., Papenberg, G., Karalija, N., … Nyberg, L. (2019). Dopamine D2/3 Binding Potential Modulates Neural Signatures of Working Memory in a Load-Dependent Fashion. Journal of Neuroscience, 39(3), 537–547.

Karalija, N., Papenberg, G., Wåhlin, A., Johansson, J., Andersson, M., Axelsson, J., … Nyberg, L. (2019). C957T -mediated Variation in Ligand Affinity Affects the Association between 11 C-raclopride Binding Potential and Cognition. Journal of Cognitive Neuroscience, 31(2), 314–325.


Salami, A., Rieckmann, A., Karalija, N., Avelar-Pereira, B., Andersson, M., Wåhlin, A., … Nyberg, L. (2018). Neurocognitive Profiles of Older Adults with Working-Memory Dysfunction. Cerebral Cortex, 28(7), 2525–2539.

Köhncke, Y., Papenberg, G., Jonasson, L., Karalija, N., Wåhlin, A., Salami, A., … Lövdén, M. (2018). Self-rated intensity of habitual physical activities is positively associated with dopamine D2/3 receptor availability and cognition. NeuroImage, 181, 605–616.

Lövdén, M., Karalija, N., Andersson, M., Wåhlin, A., Axelsson, J., Köhncke, Y., … Lindenberger, U. (2018). Latent-Profile Analysis Reveals Behavioral and Brain Correlates of Dopamine-Cognition Associations. Cerebral Cortex, 28(11), 3894–3907.


Dunås, T., Wåhlin, A., Ambarki, K., Zarrinkoob, L., Malm, J., & Eklund, A. (2017). A Stereotactic Probabilistic Atlas for the Major Cerebral Arteries. Neuroinformatics, 15(1), 101–110.

Dunås, T., Wåhlin, A., Ambarki, K., Zarrinkoob, L., Birgander, R., Malm, J., & Eklund, A. (2016). Automatic labeling of cerebral arteries in magnetic resonance angiography. Magnetic Resonance Materials in Physics, Biology and Medicine, 29(1), 39–47.

Nyberg, L., Karalija, N., Salami, A., Andersson, M., Wåhlin, A., Kaboovand, N., … Bäckman, L. (2016). Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory. Proceedings of the National Academy of Sciences, 113(28), 7918–7923.

Nevalainen, N., Riklund, K., Andersson, M., Axelsson, J., Ögren, M., Lövdén, M., … Nyberg, L. (2015). COBRA: A prospective multimodal imaging study of dopamine, brain structure and function, and cognition. Brain Research, 1612, 83–103.