{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:23:01Z","timestamp":1789647781551,"version":"4.0.0"},"reference-count":51,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7254338"],"award-info":[{"award-number":["7254338"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271459"],"award-info":[{"award-number":["82271459"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82371263"],"award-info":[{"award-number":["82371263"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460341"],"award-info":[{"award-number":["82460341"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["movementdisorders.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Movement Disorders"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Non\u2010manifesting carriers of LRRK2 and GBA pathogenic variants represent a unique cohort for investigating neuroprotective interventions at the prodromal stage of Parkinson's disease (PD). A critical challenge is identifying effective markers to predict non\u2010manifesting carriers at high risk of developing PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Our goal was to investigate whether glymphatic function is impaired in non\u2010manifesting carriers and to evaluate the potential of glymphatic dysfunction as a marker for identifying individuals at high risk of PD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used diffusion\u2010tensor imaging analysis along the perivascular space (ALPS) method to assess glymphatic function in participants from the Parkinson's Progression Markers Initiative (PPMI) dataset. Cross\u2010sectional and longitudinal changes in the ALPS index were evaluated, and baseline predictors of clinical progression were identified. The association between ALPS index and the risk of phenoconversion was examined using Kaplan\u2013Meier survival analysis and Cox proportional hazards regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Eighty non\u2010manifesting carriers of LRRK2 and GBA pathogenic variants were included. ALPS index values were reduced cross\u2010sectionally and longitudinally, and were correlated with cognitive function and daytime sleepiness scores. Baseline ALPS index values predicted a decline in Hopkins Verbal Learning Test\u2010immediate recall scores over a 3\u2010year follow\u2010up period. During follow\u2010up, 17 non\u2010manifesting carriers converted to clinically defined PD. Increasing ALPS index values were associated with a decreased risk of phenoconversion (hazard ratio [95% confidence interval]\u2009=\u20090.128 [0.029\u20130.565],\n                      <jats:italic>P<\/jats:italic>\n                      \u2009=\u20090.0013).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Glymphatic function is impaired in non\u2010manifesting carriers. Glymphatic dysfunction is associated with an increased risk of phenoconversion. The ALPS index has the potential as a marker for identifying individuals at high risk of developing PD. \u00a9 2025 International Parkinson and Movement Disorder Society.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/mds.30306","type":"journal-article","created":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T09:53:36Z","timestamp":1753696416000},"page":"2189-2198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Glymphatic Dysfunction in Non\u2010Manifesting Carriers of\n                    <scp>LRRK2<\/scp>\n                    and\n                    <scp>GBA<\/scp>\n                    Pathogenic Variants"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0399-6179","authenticated-orcid":false,"given":"Dongling","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Neurology China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Luo","sequence":"additional","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyu","family":"Li","sequence":"additional","affiliation":[{"name":"Polytechnic Institute, Zhejiang University  Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junye","family":"Yao","sequence":"additional","affiliation":[{"name":"Clinical and Technical Support Philips Healthcare  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianyi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Center for Movement Disorders, Department of Neurology Beijing Tiantan Hospital, Capital Medical University  Beijing 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