Biphasic patterns of age-related differences in dopamine D1 receptors across the adult lifespan
Jarkko Johansson,
Kristin Nordin,
Robin Pedersen,
Nina Karalija,
Goran Papenberg,
Micael Andersson,
Saana M. Korkki,
Katrine Riklund,
Marc Guitart-Masip,
Anna Rieckmann,
Lars Bäckman,
Lars Nyberg,
Alireza Salami
Affiliations
Jarkko Johansson
Department of Radiation Sciences, Diagnostic Radiology, Umeå University, 90187 Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden; Corresponding author
Kristin Nordin
Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A, 17165 Stockholm, Sweden
Robin Pedersen
Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, 90187 Umeå, Sweden; Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden
Nina Karalija
Department of Radiation Sciences, Diagnostic Radiology, Umeå University, 90187 Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden
Goran Papenberg
Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A, 17165 Stockholm, Sweden
Micael Andersson
Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, 90187 Umeå, Sweden
Saana M. Korkki
Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A, 17165 Stockholm, Sweden
Katrine Riklund
Department of Radiation Sciences, Diagnostic Radiology, Umeå University, 90187 Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden
Marc Guitart-Masip
Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A, 17165 Stockholm, Sweden; Max Planck UCL Centre for Computational Psychiatry and Ageing Research, University College London, London, UK
Anna Rieckmann
Department of Radiation Sciences, Diagnostic Radiology, Umeå University, 90187 Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, 90187 Umeå, Sweden; The Munich Center for the Economics of Aging, Max Planck Institute for Social Law and Social Policy, 80799 Munich, Germany
Lars Bäckman
Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A, 17165 Stockholm, Sweden
Lars Nyberg
Department of Radiation Sciences, Diagnostic Radiology, Umeå University, 90187 Umeå, Sweden; Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden; Department of Integrative Medical Biology, Umeå University, 90187 Umeå, Sweden; Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden
Alireza Salami
Umeå Center for Functional Brain Imaging (UFBI), Umeå University, 90187 Umeå, Sweden; Aging Research Center, Karolinska Institutet & Stockholm University, Tomtebodavägen 18A, 17165 Stockholm, Sweden; Department of Integrative Medical Biology, Umeå University, 90187 Umeå, Sweden; Wallenberg Center for Molecular Medicine, Umeå University, Umeå, Sweden
Summary: Age-related alterations in D1-like dopamine receptor (D1DR) have distinct implications for human cognition and behavior during development and aging, but the timing of these periods remains undefined. Enabled by a large sample of in vivo assessments (n = 180, age 20 to 80 years of age, 50% female), we discover that age-related D1DR differences pivot at approximately 40 years of age in several brain regions. Focusing on the most age-sensitive dopamine-rich region, we observe opposing pre- and post-forties interrelations among caudate D1DR, cortico-striatal functional connectivity, and memory. Finally, particularly caudate D1DR differences in midlife and beyond, but not in early adulthood, associate with manifestation of white matter lesions. The present results support a model by which excessive dopamine modulation in early adulthood and insufficient modulation in aging are deleterious to brain function and cognition, thus challenging a prevailing view of monotonic D1DR function across the adult lifespan.
