{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:53:41Z","timestamp":1781524421298,"version":"3.54.1"},"posted":{"date-parts":[[2026,6,11]]},"group-title":"Neurology","reference-count":41,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T00:00:00Z","timestamp":1781136000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,6,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Diabetes mellitus elevates Parkinson\u2019s disease (PD) risk, via hypothesized cerebrovascular mediation. Whether the diabetes\/prediabetes vascular-risk phenotype concentrates in cardiometabolic risk or macrovascular events across prodromal and clinically diagnosed PD remains unresolved.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To quantify the vascular-risk burden associated with diabetes\/prediabetes across the PPMI diagnostic cohorts to test whether this association differs by cohort.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Cross-sectional analysis of 413 PPMI participants (76 healthy controls, 145 prodromal PD, 192 clinically diagnosed PD) examined diabetes\/prediabetes (n = 73) and seven vascular risk factors. The Vascular Burden Score (0 to 7) was a priori partitioned into microvascular and macrovascular sub-scores. Modified Poisson regression estimated adjusted prevalence ratios (aPR), adjusted for age, sex, and body mass index. A cohort-by-diabetes interaction tested cross-cohort consistency. Sensitivity analyses incorporated nigral diffusion tensor imaging (PD-risk biomarker) and FreeSurfer white matter hypointensity volume (cerebrovascular marker).<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Diabetes\/prediabetes elevated Vascular Burden Score (\u03b2 = 0.53, 95% CI 0.29 to 0.77, p &lt; 0.001) versus non-diabetic participants, with a non-significant cohort-by-diabetes interaction (F = 0.29, p = 0.747). Three microvascular factors survived false discovery rate correction: obesity (aPR 2.28), hypertension (aPR 1.60), and hyperlipidemia (aPR 1.45). Macrovascular events showed no diabetic amplification (\u03b2 = \u22120.06, p = 0.25). In the imaging-phenotyped subset, Vascular Burden Score components contributed classifier variance distinct from nigral microstructure.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Diabetes\/prediabetes operationalize a microvascular cluster stable across prodromal and idiopathic PD. Cardiometabolic phenotyping may complement established PD-risk biomarkers (dopamine transporter SPECT, nigral diffusion), pending longitudinal validation linking vascular phenotype to dopaminergic markers.<\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.06.09.26355285","type":"posted-content","created":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T04:45:13Z","timestamp":1781239513000},"source":"Crossref","is-referenced-by-count":0,"title":["Vascular Phenotyping in Parkinson\u2019s Disease: Diabetes Mellitus Operationalizes a Microvascular Metabolic Syndrome Cluster Across PPMI Diagnostic Cohorts"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-8599-2211","authenticated-orcid":false,"given":"Alexander","family":"Belnavis","sequence":"first","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6143-9867","authenticated-orcid":false,"given":"Shannon Y.","family":"Chiu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Mayo Clinic, Phoenix, AZ 85054, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kewei","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4448-4997","authenticated-orcid":false,"suffix":"Jr.","given":"Roland J.","family":"Thorpe","sequence":"additional","affiliation":[{"name":"Program for Research on Men\u2019s Health, Johns Hopkins Center for Health Disparities Solutions, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"},{"name":"Johns Hopkins Alzheimer\u2019s Disease Resource Center for Minority Aging Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8060-0846","authenticated-orcid":false,"given":"Edward","family":"Ofori","sequence":"additional","affiliation":[{"name":"College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Parkinson Precision Medicine Initiative","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026061504150908000_2026.06.09.26355285v1.1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2019.03.001"},{"key":"2026061504150908000_2026.06.09.26355285v1.2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a009258"},{"key":"2026061504150908000_2026.06.09.26355285v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2015.09.004"},{"key":"2026061504150908000_2026.06.09.26355285v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.62"},{"key":"2026061504150908000_2026.06.09.26355285v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00131-X"},{"key":"2026061504150908000_2026.06.09.26355285v1.6","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1038\/s41531-024-00666-6","article-title":"Tackling vascular risk factors as a possible disease-modifying intervention in Parkinson\u2019s disease","volume":"10","year":"2024","journal-title":"NPJ Parkinsons Dis"},{"key":"2026061504150908000_2026.06.09.26355285v1.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2017.07.030"},{"key":"2026061504150908000_2026.06.09.26355285v1.8","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.117.020536"},{"key":"2026061504150908000_2026.06.09.26355285v1.9","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1002\/ana.26615","article-title":"Cerebral small vessel disease progression increases risk of incident parkinsonism","volume":"93","year":"2023","journal-title":"Ann Neurol"},{"key":"2026061504150908000_2026.06.09.26355285v1.10","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002082"},{"key":"2026061504150908000_2026.06.09.26355285v1.11","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.parkreldis.2020.12.025","article-title":"Cerebral small vessel disease may worsen motor function, cognition, and mood in Parkinson\u2019s disease","volume":"83","year":"2021","journal-title":"Parkinsonism Relat Disord"},{"key":"2026061504150908000_2026.06.09.26355285v1.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-018-0234-x"},{"key":"2026061504150908000_2026.06.09.26355285v1.13","unstructured":"Centers for Disease Control and Prevention. 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