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There is currently no available biomarker to predict cognitive decline in PD. Corneal confocal microscopy (CCM) has been used as a non-invasive tool for quantifying small nerve damage in PD. The present study investigated whether corneal nerve measures were associated with cognitive function in PD. Patients with PD were classified into those with normal cognitive function (PD-CN), mild cognitive impairment (PD-MCI), and dementia (PDD). Corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), and corneal nerve fiber length (CNFL) were quantified with CCM and compared with a control group. Sixty-five PD patients and thirty controls were studied. CNFD was decreased and CNBD was increased in PD patients compared to controls (<jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05). CNBD and CNBD\/CNFD ratio was higher in PD-CN compared to controls. CNFD was positively correlated with the Montreal cognitive assessment (MoCA) score (<jats:italic>r<\/jats:italic>\u2009=\u20090.683, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001), but negatively associated with unified Parkinson disease rating scale (UPDRS)-part III (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.481, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001) and total UPDRS scores (<jats:italic>r<\/jats:italic>\u2009=\u2009\u22120.401, <jats:italic>P<\/jats:italic>\u2009=\u20090.001) in PD patients. There was no correlation between CNFD and Levodopa equivalent daily dose (LEDD) (<jats:italic>r<\/jats:italic>\u2009=\u20090.176, <jats:italic>P<\/jats:italic>\u2009=\u20090.161). CNFD, CNBD, CNFL, and CNBD\/CNFD ratio was lower with increasing Hoehn and Yahr stage. PD patients show evidence of corneal nerve loss compared with controls and corneal nerve parameters are associated with the severity of cognitive and motor dysfunction in PD. CCM could serve as an objective in vivo ophthalmic imaging technique to assess neurodegeneration in PD.<\/jats:p>","DOI":"10.1038\/s41531-021-00225-3","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T10:06:24Z","timestamp":1631181984000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Corneal nerve fiber loss relates to cognitive impairment in patients with Parkinson\u2019s disease"],"prefix":"10.1038","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5470-2003","authenticated-orcid":false,"given":"Ning-Ning","family":"Che","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Huan","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guan-Xiao","family":"Ding","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si-Yuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhen-Xiang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rayaz A.","family":"Malik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5825-1927","authenticated-orcid":false,"given":"Jian-Jun","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9277-0920","authenticated-orcid":false,"given":"Hong-Qi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"225_CR1","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1038\/s41531-020-0111-7","volume":"6","author":"R Morris","year":"2020","unstructured":"Morris, R. et al. 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