COBRA
Charting the Role of Dopamine in the Aging Human Brain
The Cognition, Brain, and Aging (COBRA) study is an international collaboration between three institutions in Sweden and the Center for Lifespan Psychology at the MPI for Human Development in Berlin. It has attained the world’s first direct longitudinal evidence on the role of dopamine in the aging of brain and behavior in humans.
COBRA is a longitudinal study of 181 adults who were between 64 and 68 years of age when they were assessed for the first time in 2012 (Nevalainen et al., 2015). It currently consists of three measurement occasions, each separated by five years. COBRA examines associations among the dopamine (DA) neurotransmitter system, other brain parameters, such as grey- and white-matter volumes, white-matter microstructure, cerebral blood flow, and functional activation patterns during rest and task, and cognitive performance. The main focus of COBRA is on associations between longitudinal changes in the DA system and changes in cognitive abilities. To measure DA, participants are injected with the ligand raclopride, which binds specifically to DA D2 receptors, while undergoing positron emission tomography (PET) imaging. Under certain assumptions, DA receptor availability as assessed by raclopride can be regarded as an index of DA capacity.
COBRA involves Umeå University, the Karolinska Institutet in Stockholm, the University of Gothenburg, and the Center for Lifespan Psychology. All sites have longstanding expertise in the study of longitudinal changes in brain and behavior. Umeå University and Karolinska Institutet contribute specific expertise in dopamine imaging using PET. The University of Gothenburg and the MPI for Human Development contribute specific expertise in modeling multivariate longitudinal panel data. Scientists from all four sites meet at regular intervals, and conjointly provide the synergy required to conduct a study of this scope.
Informed by relevant theory and data (Bäckman et al., 2006; Li et al., 2001), the primary objectives of COBRA are to delineate the average pattern of DA system changes in normal aging as well as the range of between-person differences in this pattern. Given the central role of DA in cognitive, motor, and motivational aspects of behavior, gaining knowledge about normative DA changes, and about the magnitude of individual differences therein, is of fundamental importance for research on human cognitive aging. The research team hypothesizes that DA decline is exacerbated in some individuals, and that these individuals will be characterized by greater cognitive decline.
Specifically, COBRA seeks to shed light on four central questions of cognitive aging research (Nevalainen et al., 2015):
- The average degree, regional distribution, and between-person differences of age-related changes in DA capacity.
- The shared and unique contributions of changes in DA capacity, grey matter, and white matter to cognitive change in old age.
- The lead—lag relations between different neural, metabolic, and vascular correlates of cognitive decline. To assess such relations, which may differ between individuals, more than two longitudinal measurement occasions are imperative.
- The modulatory and possibly ameliorative effects of lifestyle factors, assessed by cognitive, physical, and social activity patterns, on changes in brain and behavior.
The median time interval between the first two waves was 5.0 years (range = 4.9 to 5.3), and the median time between waves two and three was 4.4 years (range = 4.0 to 5.1). Of the 181 individuals participating in the first wave, 129 individuals participated in wave 2, and 93 in wave 3. Current work focuses on 10-year changes. Initial results indicate that striatal dopamine decline is associated with cognitive aging, possibly reflecting dopamine influences via striato-thalamo-cortical loops on general cognitive functions (Lundgren et al., 2025). Future analyses will also include dopamine changes in limbic and neocortical systems, and examine lead—lag relations involving DA capacity decline.
Research Project in Brief
The Cognition, Brain, and Aging (COBRA) study
Principal Investigators:
Lars Bäckman (Professor, Aging Research Center, Karolinska Institutet, Sweden), Nina Karalija (Associate Professor, Department of Medical and Translational Biology, Umeå University, Sweden), Ulman Lindenberger (Director, Center for Lifespan Psychology, MPI for Human Development, Berlin, Germany), Martin Lövdén (Professor, Department of Psychology, University of Gothenburg, Sweden), Lars Nyberg (Professor, Center for Functional Brain Imaging, Umeå University, Sweden), and Katrine Riklund (Dean of the Medical Faculty, Umeå University, Sweden).
Currently Participating Researchers at Berlin Site:
Andreas Brandmaier, Martin Dahl, Laurenz Lammer, Ulman Lindenberger, Zoya Mooraj
Period: 2012–ongoing
Funding: e.g., Swedish Research Council, FORTE, Umeå University, the Umeå University–Karolinska Institutet Strategic Neuroscience program, Knut and Alice Wallenberg Foundation, Torsten Söderberg Foundation, Ragnar Söderberg Foundation, a donation of the Jochnick Foundation, Swedish Brain Power, Swedish Brain Foundation, Västerbotten County Council, Strategic Innovation Fund/Max Planck Society, the Gottfried Wilhelm Leibniz Prize 2010 of the German Research Foundation (DFG), and the Swedish National Infrastructure for Computing (SNIC) through the Abisko computer cluster at Umeå University.