{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T18:29:19Z","timestamp":1793816959978,"version":"4.6.1"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T00:00:00Z","timestamp":1743724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Despite the importance of clinical heterogeneity in Parkinson\u2019s disease (PD), its underlying pathophysiology remains unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>This study aimed to distinguish the association of free-water (FW) imaging data for the cholinergic nuclei with the motor subtypes of PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included 150 cases of idiopathic PD from the Parkinson\u2019s Progression Markers Initiative cohort. FW imaging, including FW-corrected diffusion tensor imaging, was used to extract structural metrics from cholinergic nucleus 4 (Ch4) in the basal forebrain and the pedunculopontine nucleus. The motor subtypes were classified as tremor-dominant (TD, <jats:italic>n<\/jats:italic>\u202f=\u202f99) and non-tremor-dominant (non-TD, <jats:italic>n<\/jats:italic>\u202f=\u202f51). Statistical analyses were performed at baseline and the 4-year follow-up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At baseline, FW value for Ch4 (FW-Ch4) was correlated with the tremor subscore, while FW-corrected fractional anisotropy in Ch4 (FA-t-Ch4) was negatively correlated with the rigidity subscore. However, the TD and non-TD groups showed no differences in cholinergic FW imaging data. Among the 84 patients who were followed-up, 36.36% (20\/55) in the TD group and 34.48% (10\/29) in the non-TD group showed a subtype shift after 4\u202fyears. Multivariate binary logistic regression analysis showed that the normalized FW value for Ch4 (nFW-Ch4) was a predictor of subtype at the 4-year follow-up (<jats:italic>p<\/jats:italic>\u202f=\u202f0.041). In the TD subgroup, both nFW-Ch4 (<jats:italic>p<\/jats:italic>\u202f=\u202f0.015) and normalized FW-corrected mean diffusivity in Ch4 (MD-t-Ch4) (<jats:italic>p<\/jats:italic>\u202f=\u202f0.013) predicted subtype stability. The area under the receiver operating characteristic curve values were 0.69 and 0.73, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Tremor and rigidity subscores were correlated with Ch4 FW imaging data. Moreover, Ch4 FW imaging predicted the motor subtype at the 4-year follow-up, especially identifying potential postural instability and gait difficulty (PIGD) subtype converters from the TD group.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1477827","type":"journal-article","created":{"date-parts":[[2025,4,4]],"date-time":"2025-04-04T16:23:57Z","timestamp":1743783837000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Association of free-water imaging data for the cholinergic nucleus with the motor function and subtypes in Parkinson\u2019s disease"],"prefix":"10.3389","volume":"16","author":[{"given":"Shanhu","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miao","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengli","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baorong","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,4]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1002\/ana.24261","article-title":"Prioritized 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