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Longitudinal Dopamine D2 Receptor Changes and Cerebrovascular Health in Aging
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.ORCID iD: 0000-0002-8603-9453
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.ORCID iD: 0000-0002-4501-4735
Aging Research Center, Karolinska Institutet & Stockholm University.
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.ORCID iD: 0000-0001-6784-1945
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2022 (English)In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 99, no 12, p. e1278-e1289Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND OBJECTIVES: Cross-sectional studies suggest marked dopamine (DA) decline in aging, but longitudinal evidence is lacking. The aim of this study was to estimate within-person decline rates for DA D2-like receptors (DRD2) in aging and examine factors that may contribute to individual differences in DRD2 decline rates.

METHODS: We investigated 5-year within-person changes in DRD2 availability in a sample of older adults. At both occasions, PET with 11C-raclopride and MRI were used to measure DRD2 availability in conjunction with structural and vascular brain integrity.

RESULTS: Longitudinal analyses of the sample (baseline: n = 181, ages: 64-68 years, 100 men and 81 women; 5-year follow-up: n = 129, 69 men and 60 women) revealed aging-related striatal and extrastriatal DRD2 decline, along with marked individual differences in rates of change. Notably, the magnitude of striatal DRD2 decline was ∼50% of past cross-sectional estimates, suggesting that the DRD2 decline rate has been overestimated in past cross-sectional studies. Significant DRD2 reductions were also observed in select extrastriatal regions, including hippocampus, orbitofrontal cortex (OFC), and anterior cingulate cortex (ACC). Distinct profiles of correlated DRD2 changes were found across several associative regions (ACC, dorsal striatum, and hippocampus) and in the reward circuit (nucleus accumbens and OFC). DRD2 losses in associative regions were associated with white matter lesion progression, whereas DRD2 losses in limbic regions were related to reduced cortical perfusion.

DISCUSSION: These findings provide the first longitudinal evidence for individual and region-specific differences of DRD2 decline in older age and support the hypothesis that cerebrovascular factors are linked to age-related dopaminergic decline.

Place, publisher, year, edition, pages
2022. Vol. 99, no 12, p. e1278-e1289
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:umu:diva-200514DOI: 10.1212/WNL.0000000000200891ISI: 000862021800023PubMedID: 35790424Scopus ID: 2-s2.0-85139739013OAI: oai:DiVA.org:umu-200514DiVA, id: diva2:1726254
Funder
Swedish Research Council, 421-2012-648Swedish Research Council, 2017-02217Torsten Söderbergs stiftelseVästerbotten County CouncilThe Swedish Brain FoundationKnut and Alice Wallenberg Foundation, 2015.0277Umeå UniversityAvailable from: 2023-01-12 Created: 2023-01-12 Last updated: 2023-01-17Bibliographically approved

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Karalija, NinaJohansson, JarkkoWåhlin, AndersSalami, AlirezaAndersson, MicaelAxelsson, JanRiklund, KatrineNyberg, Lars

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Karalija, NinaJohansson, JarkkoWåhlin, AndersSalami, AlirezaAndersson, MicaelAxelsson, JanRiklund, KatrineNyberg, Lars
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Umeå Centre for Functional Brain Imaging (UFBI)Diagnostic RadiologyDepartment of Applied Physics and ElectronicsRadiation PhysicsDepartment of Integrative Medical Biology (IMB)Wallenberg Centre for Molecular Medicine at Umeå University (WCMM)
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