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Whether MMS stem from global brain aging or pathology within motor circuits remains unresolved. The synaptic vesicle glycoprotein 2A positron emission tomography (PET) ligand <jats:sup>11<\/jats:sup>C\u2010UCB\u2010J allows the investigation of brain\u2010motor associations at the synaptic level in vivo.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>Fifty\u2010eight healthy older adults (\u226550\u2009years) were included from two monocentric control cohorts. Brain magnetic resonance imaging and <jats:sup>11<\/jats:sup>C\u2010UCB\u2010J PET data were available in 54 participants. <jats:sup>11<\/jats:sup>C\u2010UCB\u2010J PET binding was quantified by standardized uptake value ratio (SUVR) values in grey matter (GM) volumes of interest (VOIs): caudate, putamen, globus pallidus, substantia nigra, thalamus, cerebellum, and the frontal, parietal, temporal, and occipital cortex. Multiple linear regression analyses were performed with Movement Disorder Society\u2010Unified Parkinson's Disease Rating Scale (MDS\u2010UPDRS) part III score measuring MMS as the dependent variable and mean SUVR values in each VOI as the independent variable with age, Fazekas score (white matter lesion [WML] load), VOI and cohort as covariates.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Participants (68\u2009\u00b1\u20097.5\u2009years; 52% female) had an average MDS\u2010UPDRS part III score of 3.3\u2009\u00b1\u20092.8. The MDS\u2010UPDRS part III score was inversely associated with synaptic density, independently of WML load or GM volume, in the caudate, substantia nigra, thalamus, cerebellum, and parietal, occipital, temporal cortex. Cohen's f<jats:sup>2<\/jats:sup> showed moderate effect sizes for subcortical (range, 0.30\u20130.35), cortical (0.28\u20130.35) and cerebellar VOIs (0.31).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>MMS in healthy aging are associated with lower synaptic density throughout the brain. \u00a9 2023 International Parkinson and Movement Disorder Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mds.29570","type":"journal-article","created":{"date-parts":[[2023,8,14]],"date-time":"2023-08-14T02:54:56Z","timestamp":1691981696000},"page":"1786-1794","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Mild Motor Signs in Healthy Aging Are Associated with Lower Synaptic Density in the Brain"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1324-6945","authenticated-orcid":false,"given":"Margot G.A.","family":"Van 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