{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,15]],"date-time":"2026-08-15T09:26:12Z","timestamp":1786785972480,"version":"build-2736575974"},"reference-count":44,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:00:00Z","timestamp":1772755200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disord Clin Pract"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Visuospatial deficits in Parkinson's disease (PD) often precede dementia and complicate daily functioning. Alzheimer's disease (AD) pathology and \u03b1\u2010synuclein aggregation frequently co\u2010occur in PD, but their combined impact on cognition is unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To examine whether AD biomarker burden relates to visuospatial performance in PD, whether this effect differs by \u03b1\u2010synuclein status, and whether AD biomarkers mediate age\u2010related decline.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We analyzed 416 participants from the Parkinson's Progression Markers Initiative. AD biomarker burden was indexed by the cerebrospinal fluid pTau181\/A\u03b242 ratio; \u03b1\u2010synuclein aggregation was assessed using seed amplification assay. Models adjusted for age, sex, education, and motor severity. Sensitivity analyses included genetic stratification and subgroup exclusion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Higher AD biomarker burden was associated with poorer visuospatial performance and delayed recall. In participants with concurrent biomarker data (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009246), AD burden interacted with \u03b1\u2010synuclein status to predict worse visuospatial outcomes, with the greatest impairment observed in individual's positive for both biomarkers. Mediation analysis indicated that AD biomarker burden accounts for approximately 10\u201314% of the age effect on visuospatial performance.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>AD and \u03b1\u2010synuclein biomarkers show associations consistent with synergistic effects on visuospatial cognition in PD. These findings are exploratory and require replication in pre\u2010specified independent cohorts. However, if validated, testing both biomarkers could help identify individuals at higher risk of early visuospatial decline and inform hypothesis\u2010driven stratification in future clinical trials.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mdc3.70576","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T13:43:05Z","timestamp":1772977385000},"page":"1861-1875","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Alzheimer's Biomarkers and Visuospatial Cognition in Parkinson's Disease: Modification by \u03b1\u2010Synuclein and Mediation of Age Effects"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6474-2666","authenticated-orcid":false,"given":"David","family":"Ledingham","sequence":"first","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"},{"name":"Neurosciences Newcastle Upon Tyne NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahana","family":"Sathyanarayana","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte B.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Iredale","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Foster","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debra","family":"Galley","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meher","family":"Lad","sequence":"additional","affiliation":[{"name":"Neurosciences Newcastle Upon Tyne NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Baker","sequence":"additional","affiliation":[{"name":"Neurosciences Newcastle Upon Tyne NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6801-6194","authenticated-orcid":false,"given":"Nicola","family":"Pavese","sequence":"additional","affiliation":[{"name":"Clinical Ageing Research Unit Newcastle University, Campus for Ageing and Vitality  Newcastle upon Tyne UK"},{"name":"Neurosciences Newcastle Upon Tyne NHS Foundation Trust  Newcastle upon Tyne UK"},{"name":"Translational and Clinical Research Institute, The Medical School Newcastle University  Newcastle upon Tyne UK"},{"name":"Department of Nuclear Medicine and PET Centre Aarhus University Hospital  Aarhus 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