Cognition, brain, and aging (COBRA)

PI: Lars Bäckman, lars.backman.1@ki.se

Because we lack longitudinal data on the degree of average age-related change in dopamine availability, grey matter, and white matter, the current foundations for research on aging, brain, and cognition are imperfect and possibly erroneous. Moreover, the shared and unique contributions of changes in dopamine, grey matter, and white matter to changes in cognitive performance in old age remain unknown. A better understanding of age-related change in dopamine availability, grey matter, and white matter is imperative because changes in these neural substrates are likely to be related and therefore must be assessed jointly to evaluate their relative contributions to cognitive decline in aging.

Additionally, we do not know which of the candidate neural correlates of cognitive decline (dopamine, grey matter, or white matter) first displays signs of change in old age. It is also unclear whether one brain change is associated with subsequent changes in other brain measures and thus acts as a primary mechanism of decline in brain and cognition. Our main hypothesis is that age-related changes in dopamine precede changes in the other assessed brain indices and serve as the most powerful antecedent of age-related cognitive changes.

Finally, the lifestyle factors associated with changes in the brain parameters assessed are largely unknown. New knowledge here is critical because identifying key lifestyle factors that modify brain and cognition in old age will inform the focus of intervention and prevention strategies.

COBRA includes approximately 180 people age 63 to 67 years at baseline. Variables are measured three times over the nine-year study period. PET and MRI are used to assess multiple brain measures, including dopamine D2 receptors, markers of grey- and white-matter integrity, and functional networks. Cognition is evaluated using measures of working memory, episodic memory, and speed, and a comprehensive lifestyle questionnaire is administered.

COBRA involves scientists from ARC, Umeå University, and the Max Planck Institute for Human Development in Berlin. It is funded by the Stichtning af Jochnick Foundation.