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":"轻度认知障碍和痴呆患者角膜内皮细胞形态与神经退行性变的关系。","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":"<div>\n \n \n <section>\n \n <h3> INTRODUCTION</h3>\n \n <p>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>\n </section>\n \n <section>\n \n <h3> METHODS</h3>\n \n <p>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>\n </section>\n \n <section>\n \n <h3> RESULTS</h3>\n \n <p>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>\n </section>\n \n <section>\n \n <h3> DISCUSSION</h3>\n \n <p>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>\n </section>\n \n <section>\n \n <h3> Highlights</h3>\n \n <div>\n <ul>\n \n <li>Corneal endothelial cell density is significantly reduced in patients with dementia.</li>\n \n <li>Corneal nerve fiber density, branch density, and length are lower in subjects with mild cognitive impairment (MCI) and dementia.</li>\n \n <li>Corneal endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy.</li>\n \n <li>Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.</li>\n \n <li>Reduced corneal endothelial cell density partially mediates the effects of age and diabetes on corneal nerve fiber loss.</li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":53225,"journal":{"name":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","volume":"11 1","pages":""},"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":"{\"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\":\"<div>\\n \\n \\n <section>\\n \\n <h3> INTRODUCTION</h3>\\n \\n <p>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>\\n </section>\\n \\n <section>\\n \\n <h3> METHODS</h3>\\n \\n <p>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>\\n </section>\\n \\n <section>\\n \\n <h3> RESULTS</h3>\\n \\n <p>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>\\n </section>\\n \\n <section>\\n \\n <h3> DISCUSSION</h3>\\n \\n <p>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>\\n </section>\\n \\n <section>\\n \\n <h3> Highlights</h3>\\n \\n <div>\\n <ul>\\n \\n <li>Corneal endothelial cell density is significantly reduced in patients with dementia.</li>\\n \\n <li>Corneal nerve fiber density, branch density, and length are lower in subjects with mild cognitive impairment (MCI) and dementia.</li>\\n \\n <li>Corneal endothelial cell loss and hypertrophy are associated with cortical gray matter atrophy.</li>\\n \\n <li>Corneal nerve and endothelial cell abnormalities could act as biomarkers for neurovascular pathology in dementia.</li>\\n \\n <li>Reduced corneal endothelial cell density partially mediates the effects of age and diabetes on corneal nerve fiber loss.</li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":53225,\"journal\":{\"name\":\"Alzheimer''s and Dementia: Translational Research and Clinical Interventions\",\"volume\":\"11 1\",\"pages\":\"\"},\"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://onlinelibrary.wiley.com/doi/10.1002/trc2.70025\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer''s and Dementia: Translational Research and Clinical Interventions","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/trc2.70025","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
角膜共聚焦显微镜（CCM）检测轻度认知障碍（MCI）和痴呆的神经退行性变，并识别MCI患者发展为痴呆。本研究评估了MCI和痴呆患者角膜内皮细胞（CEC）形态异常是否与角膜神经形态、脑容量、脑缺血和认知障碍有关。方法：无认知障碍（NCI）、轻度认知障碍（MCI）和痴呆的参与者采用CCM量化角膜内皮细胞密度（CECD）和面积（CECA）、角膜神经纤维形态、磁共振成像（MRI）脑容量和脑缺血严重程度。结果：114名参与者中，14人患有NCI， 77人患有MCI， 23人患有痴呆。痴呆患者的ced（1971.3±594.6 vs 2316.1±499.5 cells/mm2, p < 0.05）明显低于NCI组。ccd和CECA在MCI组和NCI组之间具有可比性（p = 0.13-0.65）。MCI组和痴呆组的角膜神经纤维密度（CNFD）（31.7±5.6 vs 24.5±9.2和17.3±5.3纤维/mm2， p < 0.01）、角膜神经分支密度（CNBD）（111.8±58.1 vs 50.4±36.4和52.7±21.3支/mm2， p < 0.0001）和角膜神经纤维长度（CNFL）（24.6±6.6 vs 16.5±6.8和16.2±5.0 mm/mm2, p < 0.0001）均低于NCI组。CECA降低部分介导了年龄和糖尿病对CNFL降低的影响（p < 0.05），而CECA调整后失去了其显著性（p = 0.20）。CEC形态学不影响角膜神经纤维丢失与MCI/痴呆之间的关系。CECD和CECA与脑缺血病变（p = 0.21-0.47）、痴呆（p = 0.11-0.35）、认知能力下降（p = 0.37-0.38）无显著相关性。然而，较低的CECD和较高的CECA与皮质灰质体积减少相关（p < 0.05-0.01）。讨论：CEC丢失发生在痴呆患者中，内皮细胞丢失和肥大都与皮质灰质萎缩有关。CNF丢失发生在轻度认知损伤和痴呆患者中。角膜神经和内皮细胞异常可作为痴呆患者神经血管病理的生物标志物。重点：痴呆患者角膜内皮细胞密度显著降低。轻度认知障碍（MCI）和痴呆患者的角膜神经纤维密度、分支密度和长度较低。角膜内皮细胞的丢失和肥大与皮质灰质萎缩有关。角膜神经和内皮细胞异常可作为痴呆患者神经血管病理的生物标志物。角膜内皮细胞密度降低在一定程度上介导了年龄和糖尿病对角膜神经纤维丧失的影响。
Association of corneal endothelial cell morphology with neurodegeneration in mild cognitive impairment and dementia
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.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
