Georgios Ponirakis, Hanadi Al Hamad, Alaa S Al-Waisy, Ioannis N Petropoulos, Adnan Khan, Hoda Gad, Mani Chandran, Masharig Gadelseed, Salah Mahmoud, Ahmed Elsotouhy, Marwan Ramadan, Shafi Khan, Rustu E Akcan, Priya V Gawhale, Noushad Thodi, Tala Nakouzi, Moayad Homssi, Nebras Hadid, Aisha Al Obaidan, Rawan Hussein, Ahmed Own, Ashfaq Shuaib, Rayaz A Malik
{"title":"Association of corneal endothelial cell morphology with neurodegeneration in mild cognitive impairment and dementia.","authors":"Georgios Ponirakis, Hanadi Al Hamad, Alaa S Al-Waisy, Ioannis N Petropoulos, Adnan Khan, Hoda Gad, Mani Chandran, Masharig Gadelseed, Salah Mahmoud, Ahmed Elsotouhy, Marwan Ramadan, Shafi Khan, Rustu E Akcan, Priya V Gawhale, Noushad Thodi, Tala Nakouzi, Moayad Homssi, Nebras Hadid, Aisha Al Obaidan, Rawan Hussein, Ahmed Own, Ashfaq Shuaib, Rayaz A Malik","doi":"10.1002/trc2.70025","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Corneal confocal microscopy (CCM) detects neurodegeneration in mild cognitive impairment (MCI) and dementia and identifies subjects with MCI who develop dementia. This study assessed whether abnormalities in corneal endothelial cell (CEC) morphology are related to corneal nerve morphology, brain volumetry, cerebral ischemia, and cognitive impairment in MCI and dementia.</p><p><strong>Methods: </strong>Participants with no cognitive impairment (NCI), MCI, and dementia underwent CCM to quantify corneal endothelial cell density (CECD) and area (CECA), corneal nerve fiber morphology, magnetic resonance imaging (MRI) brain volumetry, and severity of brain ischemia.</p><p><strong>Results: </strong>Of the 114 participants, 14 had NCI, 77 had MCI, and 23 had dementia. CECD (1971.3 ± 594.6 vs 2316.1 ± 499.5 cells/mm<sup>2</sup>, <i>p</i> < 0.05) was significantly lower in the dementia compared to the NCI group. CECD and CECA were comparable between the MCI and NCI groups (<i>p</i> = 0.13-0.65). Corneal nerve fiber density (CNFD) (31.7 ± 5.6 vs 24.5 ± 9.2 and 17.3 ± 5.3 fibers/mm<sup>2</sup>, <i>p</i> < 0.01), corneal nerve branch density (CNBD) (111.8 ± 58.1 vs 50.4 ± 36.4 and 52.7 ± 21.3 branches/mm<sup>2</sup>, <i>p</i> < 0.0001), and corneal nerve fiber length (CNFL) (24.6 ± 6.6 vs 16.5 ± 6.8 and 16.2 ± 5.0 mm/mm<sup>2</sup>, <i>p</i> < 0.0001) were lower in the MCI and dementia groups compared to the NCI group. Lower CECD partially mediated the impact of age and diabetes on CNFL reduction (<i>p</i> < 0.05), whereas CECA lost its significance after adjustment (<i>p</i> = 0.20). CEC morphology does not affect the association between corneal nerve fiber loss and MCI/dementia. CECD and CECA had no significant association with cerebral ischemic lesions (<i>p</i> = 0.21-0.47), dementia (<i>p</i> = 0.11-0.35), or cognitive decline (<i>p</i> = 0.37-0.38). However, lower CECD and higher CECA were associated with decreased cortical gray matter volume (<i>p</i> < 0.05-0.01).</p><p><strong>Discussion: </strong>CEC loss occurs in patients with dementia, and both endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy. CNF loss occurs in individuals with MCI and dementia. Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.</p><p><strong>Highlights: </strong>Corneal endothelial cell density is significantly reduced in patients with dementia.Corneal nerve fiber density, branch density, and length are lower in subjects with mild cognitive impairment (MCI) and dementia.Corneal endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy.Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.Reduced corneal endothelial cell density partially mediates the effects of age and diabetes on corneal nerve fiber loss.</p>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":"e70025"},"PeriodicalIF":4.9000,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11696023/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1002/trc2.70025","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Introduction: Corneal confocal microscopy (CCM) detects neurodegeneration in mild cognitive impairment (MCI) and dementia and identifies subjects with MCI who develop dementia. This study assessed whether abnormalities in corneal endothelial cell (CEC) morphology are related to corneal nerve morphology, brain volumetry, cerebral ischemia, and cognitive impairment in MCI and dementia.
Methods: Participants with no cognitive impairment (NCI), MCI, and dementia underwent CCM to quantify corneal endothelial cell density (CECD) and area (CECA), corneal nerve fiber morphology, magnetic resonance imaging (MRI) brain volumetry, and severity of brain ischemia.
Results: Of the 114 participants, 14 had NCI, 77 had MCI, and 23 had dementia. CECD (1971.3 ± 594.6 vs 2316.1 ± 499.5 cells/mm2, p < 0.05) was significantly lower in the dementia compared to the NCI group. CECD and CECA were comparable between the MCI and NCI groups (p = 0.13-0.65). Corneal nerve fiber density (CNFD) (31.7 ± 5.6 vs 24.5 ± 9.2 and 17.3 ± 5.3 fibers/mm2, p < 0.01), corneal nerve branch density (CNBD) (111.8 ± 58.1 vs 50.4 ± 36.4 and 52.7 ± 21.3 branches/mm2, p < 0.0001), and corneal nerve fiber length (CNFL) (24.6 ± 6.6 vs 16.5 ± 6.8 and 16.2 ± 5.0 mm/mm2, p < 0.0001) were lower in the MCI and dementia groups compared to the NCI group. Lower CECD partially mediated the impact of age and diabetes on CNFL reduction (p < 0.05), whereas CECA lost its significance after adjustment (p = 0.20). CEC morphology does not affect the association between corneal nerve fiber loss and MCI/dementia. CECD and CECA had no significant association with cerebral ischemic lesions (p = 0.21-0.47), dementia (p = 0.11-0.35), or cognitive decline (p = 0.37-0.38). However, lower CECD and higher CECA were associated with decreased cortical gray matter volume (p < 0.05-0.01).
Discussion: CEC loss occurs in patients with dementia, and both endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy. CNF loss occurs in individuals with MCI and dementia. Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.
Highlights: Corneal endothelial cell density is significantly reduced in patients with dementia.Corneal nerve fiber density, branch density, and length are lower in subjects with mild cognitive impairment (MCI) and dementia.Corneal endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy.Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.Reduced corneal endothelial cell density partially mediates the effects of age and diabetes on corneal nerve fiber loss.
期刊介绍：
Alzheimer''s & Dementia: Translational Research & Clinical Interventions (TRCI) is a peer-reviewed, open access,journal from the Alzheimer''s Association®. The journal seeks to bridge the full scope of explorations between basic research on drug discovery and clinical studies, validating putative therapies for aging-related chronic brain conditions that affect cognition, motor functions, and other behavioral or clinical symptoms associated with all forms dementia and Alzheimer''s disease. The journal will publish findings from diverse domains of research and disciplines to accelerate the conversion of abstract facts into practical knowledge: specifically, to translate what is learned at the bench into bedside applications. The journal seeks to publish articles that go beyond a singular emphasis on either basic drug discovery research or clinical research. Rather, an important theme of articles will be the linkages between and among the various discrete steps in the complex continuum of therapy development. For rapid communication among a multidisciplinary research audience involving the range of therapeutic interventions, TRCI will consider only original contributions that include feature length research articles, systematic reviews, meta-analyses, brief reports, narrative reviews, commentaries, letters, perspectives, and research news that would advance wide range of interventions to ameliorate symptoms or alter the progression of chronic neurocognitive disorders such as dementia and Alzheimer''s disease. The journal will publish on topics related to medicine, geriatrics, neuroscience, neurophysiology, neurology, psychiatry, clinical psychology, bioinformatics, pharmaco-genetics, regulatory issues, health economics, pharmacoeconomics, and public health policy as these apply to preclinical and clinical research on therapeutics.
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