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Cerebral small-vessel disease severity, hypertension, and body mass index forecast striatal dopamine D2-receptor decline rates in aging
Umeå University, Faculty of Medicine, Department of Medical and Translational Biology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).ORCID iD: 0000-0002-8603-9453
Umeå University, Faculty of Medicine, Department of Medical and Translational Biology. Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention. Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics.ORCID iD: 0000-0001-6784-1945
Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI). Umeå University, Faculty of Medicine, Department of Diagnostics and Intervention.ORCID iD: 0000-0002-4501-4735
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2025 (English)In: Neurobiology of Aging, ISSN 0197-4580, E-ISSN 1558-1497, Vol. 156, p. 30-39Article in journal (Refereed) Published
Abstract [en]

Normal aging is associated with decline in dopamine function. Factors associated with individual differences in dopamine decline rates remain unclear but are important to map to spare dopamine-related functions, such as cognition. Here we focused on manifestations of cerebral small-vessel disease from magnetic resonance imaging (white-matter lesions, lacunes, and perivascular space dilation) and vascular risk factors (e.g., hypertension, body mass index (BMI), and hyperlipidemia). We assessed striatal dopamine D2-like receptor (DRD2) reductions across five years in healthy, older adults (n = 129, ages: 64–68 years at baseline) using 11C-raclopride/positron emission tomography. Manifestations of confluent lesions and lacunes at baseline had additive effects on DRD2 decline. Individuals with both manifestations showed fastest DRD2 decline rates (∼ −4 %), followed by those with one manifestation (∼ −2 %), whereas individuals spared of confluent lesions and lacunes showed stable DRD2 levels over time (∼ 0 % change). Furthermore, individuals with confluent lesions or lacunes showed more marked decline in perceptual speed performance, as compared to individuals spared of these manifestations (p < 0.05). Higher systolic blood pressure and lower BMI at baseline were associated with faster 5-year DRD2 decline in the putamen (r = -0.17, p < 0.05) and caudate (r = 0.23, p < 0.05), respectively. Together, confluent lesions and lacunes explained up to 8 % of striatal DRD2 change, and up to 10 % when adding hypertension and BMI to the model. These findings suggest that hallmarks of SVD and certain vascular risk factors predispose faster DRD2 decline in aging and may thus serve as factors to consider in future interventions.

Place, publisher, year, edition, pages
Elsevier, 2025. Vol. 156, p. 30-39
Keywords [en]
Aging, Cerebral small-vessel disease, Cognition, Dopamine D2-like receptor, Hypertension, Longitudinal
National Category
Neurosciences Geriatrics
Identifiers
URN: urn:nbn:se:umu:diva-243544DOI: 10.1016/j.neurobiolaging.2025.08.001PubMedID: 40819487Scopus ID: 2-s2.0-105013119953OAI: oai:DiVA.org:umu-243544DiVA, id: diva2:1994160
Funder
Swedish Research Council, 421-2012-648Swedish Research Council, 2017-02217Swedish Research Council, 2022-01804Umeå UniversityKnut and Alice Wallenberg Foundation, 2015.0277Ragnar Söderbergs stiftelseJonas and Christina af Jochnick FoundationAlzheimerfonden, AF-967710Riksbankens Jubileumsfond, P20–0779Region VästerbottenMax Planck SocietySwedish National Infrastructure for Computing (SNIC)Available from: 2025-09-02 Created: 2025-09-02 Last updated: 2025-09-02Bibliographically approved

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Karalija, NinaCrine, VanessaWåhlin, AndersJohansson, JarkkoAndersson, MicaelRiklund, KatrineNyberg, Lars

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Karalija, NinaCrine, VanessaWåhlin, AndersJohansson, JarkkoAndersson, MicaelRiklund, KatrineNyberg, Lars
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Department of Medical and Translational BiologyUmeå Centre for Functional Brain Imaging (UFBI)Department of Diagnostics and InterventionDepartment of Applied Physics and Electronics
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Neurobiology of Aging
NeurosciencesGeriatrics

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