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We hypothesized that dopamine decline is exacerbated in older adults with higher measures of astrocyte reactivity and cerebral SVD, and that reduced dopamine integrity would be the strongest predictor of lower cognitive performance. Healthy adults (\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200955, ages: 60\u201379\u2009years) underwent positron emission tomography with ligands\n                    <jats:sup>18<\/jats:sup>\n                    F-FE-PE2I to estimate levels of dopamine transporters (DAT) and\n                    <jats:sup>11<\/jats:sup>\n                    C-L-deprenyl-D\n                    <jats:sub>2<\/jats:sub>\n                    to estimate levels of monoamine oxidase B (MAO-B)\u2014a protein expressed to some degree by neurons but mainly by astrocytes. Cerebral SVD was assessed by white matter lesion volumes from magnetic resonance images. General cognition was evaluated via tests of episodic memory, working memory, and perceptual speed. Contrary to expectations, increased MAO-B levels (indicative of astrocyte reactivity) were associated with higher DAT availability (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u20090.53,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and reduced white matter lesion volumes (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u2009\u22120.33,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.021). Reduced DAT availability was more strongly related to reduced MAO-B (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u20090.47,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&lt;\u20090.001) than white matter lesion volumes (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u2009\u22120.22,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009&gt;\u20090.05), and only DAT was a significant predictor of cognition (\n                    <jats:italic toggle=\"yes\">r<\/jats:italic>\n                    \u2009=\u20090.36,\n                    <jats:italic toggle=\"yes\">p<\/jats:italic>\n                    \u2009=\u20090.032). These findings underscore the critical role of dopamine for cognition and indicate reduced glial function to underlie dopaminergic losses.\n                  <\/jats:p>","DOI":"10.1177\/0271678x261441065","type":"journal-article","created":{"date-parts":[[2026,4,11]],"date-time":"2026-04-11T08:21:40Z","timestamp":1775895700000},"page":"1983-1995","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["The role of dopamine decline, astrocyte reactivity and cerebral small-vessel disease in cognitive aging"],"prefix":"10.1177","volume":"46","author":[{"given":"Vanessa","family":"Crine","sequence":"first","affiliation":[{"name":"Department of Medical and Translational Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jarkko","family":"Johansson","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Diagnostics and Intervention, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Ericsson","sequence":"additional","affiliation":[{"name":"Department of Medical and Translational Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"W\u00e5hlin","sequence":"additional","affiliation":[{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Diagnostics and Intervention, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Department of Applied Physics and Electronics, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3731-3612","authenticated-orcid":false,"given":"Jan","family":"Axelsson","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Intervention, Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micael","family":"Anderssson","sequence":"additional","affiliation":[{"name":"Department of Medical and Translational Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for Functional Brain Imaging (UFBI), Ume\u00e5 University, Ume\u00e5, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Nyberg","sequence":"additional","affiliation":[{"name":"Department of Medical and Translational Biology, Ume\u00e5 University, Ume\u00e5, Sweden"},{"name":"Ume\u00e5 Center for 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