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DyNAMiC: A prospective longitudinal study of dopamine and brain connectomes: A new window into cognitive aging
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).ORCID iD: 0000-0003-4157-1638
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM). Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Statistics.ORCID iD: 0000-0003-2135-9963
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Wallenberg Centre for Molecular Medicine at Umeå University (WCMM).
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).ORCID iD: 0000-0002-6041-5537
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2022 (English)In: Journal of Neuroscience Research, ISSN 0360-4012, E-ISSN 1097-4547, Vol. 100, no 6, p. 1296-1320Article in journal (Refereed) Published
Abstract [en]

Concomitant exploration of structural, functional, and neurochemical brain mechanisms underlying age-related cognitive decline is crucial in promoting healthy aging. Here, we present the DopamiNe, Age, connectoMe, and Cognition (DyNAMiC) project, a multimodal, prospective 5-year longitudinal study spanning the adult human lifespan. DyNAMiC examines age-related changes in the brain’s structural and functional connectome in relation to changes in dopamine D1 receptor availability (D1DR), and their associations to cognitive decline. Critically, due to the complete lack of longitudinal D1DR data, the true trajectory of one of the most age-sensitive dopamine systems remains unknown. The first DyNAMiC wave included 180 healthy participants (20–80 years). Brain imaging included magnetic resonance imaging assessing brain structure (white matter, gray matter, iron), perfusion, and function (during rest and task), and positron emission tomography (PET) with the [11C]SCH23390 radioligand. A subsample (n = 20, >65 years) was additionally scanned with [11C]raclopride PET measuring D2DR. Age-related variation was evident for multiple modalities, such as D1DR; D2DR, and performance across the domains of episodic memory, working memory, and perceptual speed. Initial analyses demonstrated an inverted u-shaped association between D1DR and resting-state functional connectivity across cortical network nodes, such that regions with intermediate D1DR levels showed the highest levels of nodal strength. Evident within each age group, this is the first observation of such an association across the adult lifespan, suggesting that emergent functional architecture depends on underlying D1DR systems. Taken together, DyNAMiC is the largest D1DR study worldwide, and will enable a comprehensive examination of brain mechanisms underlying age-related cognitive decline.

Place, publisher, year, edition, pages
John Wiley & Sons, 2022. Vol. 100, no 6, p. 1296-1320
Keywords [en]
aging, cognition, connectome, dopamine, lifespan, PET
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-193314DOI: 10.1002/jnr.25039ISI: 000769326800001PubMedID: 35293013Scopus ID: 2-s2.0-85126323267OAI: oai:DiVA.org:umu-193314DiVA, id: diva2:1647981
Funder
Swedish Research Council, 2016– 01936Knut and Alice Wallenberg FoundationRiksbankens Jubileumsfond, P20-0515Available from: 2022-03-29 Created: 2022-03-29 Last updated: 2023-04-25Bibliographically approved

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Nordin, KristinGorbach, TetianaPedersen, RobinPanes Lundmark, VaniaJohansson, JarkkoAndersson, MicaelMcNulty, CharlotteRiklund, KatrineWåhlin, AndersSalami, Alireza

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Nordin, KristinGorbach, TetianaPedersen, RobinPanes Lundmark, VaniaJohansson, JarkkoAndersson, MicaelMcNulty, CharlotteRiklund, KatrineWåhlin, AndersSalami, Alireza
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Umeå Centre for Functional Brain Imaging (UFBI)Department of Integrative Medical Biology (IMB)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)StatisticsDiagnostic RadiologyRadiation Physics
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