Association of corneal nerve fiber measures with cognitive function in dementia

Ponirakis, Georgios; Hamad, Hanadi Al; Sankaranarayanan, Anoop; Khan, Adnan; Chandran, Mani; Ramadan, Marwan; Tosino, Rhia; Gawhale, Priya V; Alobaidi, Maryam; AlSulaiti, Essa; Elsotouhy, Ahmed; Elorrabi, Marwa; Khan, Shafi; Nadukkandiyil, Navas; Osman, Susan; Thodi, Noushad; Almuhannadi, Hamad; Gad, Hoda; Mahfoud, Ziyad; Al-Shibani, Fatima; Petropoulos, Ioannis N.; Own, Ahmed; Kuwari, Maryam Al; Shuaib, Ashfaq; Malik, Rayaz A.

doi:10.1002/acn3.746

Cited by 64 publications

(90 citation statements)

References 44 publications

(62 reference statements)

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“…Corneal confocal microscopy (CCM) is a noninvasive ophthalmic imaging technique for rapid, high-resolution imaging of corneal nerves. This technique has identified axonal loss in diabetes [21][22][23], impaired glucose tolerance [24], other peripheral neuropathies [25,26], Parkinson's disease [27], amyotrophic lateral sclerosis [28], multiple sclerosis [29] and dementia [30]. More recently we have shown a significant loss of corneal nerves in patients with TIA [31] and acute ischemic stroke [32][33][34], which was associated with elevated triglycerides and HbA 1c .…”

Section: Introductionmentioning

confidence: 88%

Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke

et al. 2020

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Objectives Corneal nerve damage may be a surrogate marker for the risk of ischemic stroke. This study was undertaken to determine if there is greater corneal nerve damage in patients with recurrent ischemic stroke. Methods Corneal confocal microscopy (CCM) was used to quantify corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal nerve fiber length (CNFL) and corneal nerve fiber tortuosity (CNFT) in 31 patients with recurrent ischemic stroke, 165 patients with a first acute ischemic stroke and 23 healthy control subjects. Results Triglycerides (P = 0.004, P = 0.017), systolic BP (P = 0.000, P = 0.000), diastolic BP (P = 0.000, P = 0.000) and HbA 1c (P = 0.000, P = 0.000) were significantly higher in patients with first and recurrent stroke compared to controls. There was no difference in age, BMI, HbA 1c , total cholesterol, triglycerides, LDL, HDL, systolic and diastolic BP between patients with a first and recurrent ischemic stroke. However, CNFD was significantly lower (24.98±7.31 vs 29.07±7.58 vs 37.91±7.13, P<0.05) and CNFT was significantly higher (0.085±0.042 vs 0.064±0.037 vs 0.039±0.022, P<0.05) in patients with recurrent stroke compared to first stroke and healthy controls. CNBD (42.21±24.65 vs 50.46±27.68 vs 87.24±45.85, P<0.001) and CNFL (15.66±5.70, P<0.001 vs 17.38±5.06, P = 0.003) were equally reduced in patients with first and recurrent stroke compared to controls (22.72±5.14).

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Section: Introductionmentioning

confidence: 88%

Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke

et al. 2020

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“…In this study, the left and right MTA scores could not distinguish subjects with NCI from MCI. (21) reported corneal nerve loss and reasonable diagnostic accuracy in a small cohort of subjects with MCI and dementia. In the present study with a greater number of participants we show improved diagnostic accuracy with an AUC (86% vs 73%), sensitivity (81% vs 70%) and speci city (81% vs 75%) for MCI and a comparable AUC (85% vs 86%) and sensitivity (79% vs 85%) but improved speci city (91% vs 75%) for dementia.…”

Section: Discussionmentioning

confidence: 82%

Corneal nerve and brain imaging in mild cognitive impairment and dementia: A cross-sectional study

Al-Janahi

Ponirakis

Hamad

et al. 2020

Preprint

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Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted biomarker of Alzheimer’s disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging biomarker of neurodegeneration. We sought to determine the diagnostic accuracy of CCM to distinguish mild cognitive impairment (MCI) and dementia from no cognitive impairment (NCI) in relation to MTA rating.Methods: Subjects aged 60-85 with NCI, MCI and dementia were recruited from the geriatric and memory clinic in Rumailah Hospital, Doha, Qatar between 18/09/16 and 31/07/19. The diagnosis of MCI and dementia were based on the International Classification of Diseases (ICD-10) criteria. Subjects underwent cognitive screening using the Montreal Cognitive Assessment (MoCA), CCM and MTA rating on MRI. Statistical tests used were ANOVA with Bonferroni’s post hoc test, kappa statistics and receiver operating characteristic (ROC) curve analysis. A two-tailed P value of ≤0.05 was considered significant.Results: 182 subjects with NCI (n=36), MCI (n=80) and dementia (n=66), including AD (n=19, 28.8%), VaD (n=13, 19.7%) and combined AD (n=34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 vs 24.5±9.6 vs 20.8±9.3, p<0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 vs 59.3±35.7 vs 53.9±38.7, p<0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 vs 17.2±6.5 vs 15.8±7.4, p<0.0001), in subjects with MCI and dementia compared to NCI. The MTA rating in the dementia group was significantly higher compared with the NCI and MCI group in the right (1.9±1.0 vs 0.5±0.6 and 0.6±0.8, p<0.0001) and left (2.1±1.1 vs 0.6±0.7 and 0.8±0.8, p<0.0001) hemispheres. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL vs MTA-right and -left for MCI was 78% (67-90%), 82% (72-92%), 86% (77-95%) vs 53% (36-69%) and 40% (25-55%), respectively, and for dementia it was 85% (76-94%), 84% (75-93%), 85% (76-94%) vs 86% (76-96%) and 82% (72-92%), respectively.Conclusions: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration was high and comparable with MTA rating for dementia and superior to MTA rating for MCI.

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“…Recently, we showed that reduced corneal nerve ber density was associated with ischemic lesions in patients with acute ischemic stroke after adjusting for age, diabetes, gender, dyslipidemia and smoking [14]. We have demonstrated signi cant corneal nerve loss in patients with MCI and dementia, which was associated with the severity of cognitive impairment and disability [17]. Moreover we have recently shown that the diagnostic accuracy of CCM was high and comparable with MRI based medial temporal lobe atrophy (MTA) rating for dementia but was superior in MCI [18].…”

Section: Discussionmentioning

confidence: 84%

“…Furthermore, corneal nerve loss has been associated with the presence of ischemic lesions in patients with acute ischemic stroke after adjusting for age, diabetes, gender, dyslipidemia and smoking [14]. We have also previously reported that patients with mild cognitive impairment (MCI) and dementia have signi cant corneal nerve loss which is associated with the severity of cognitive impairment and disability [17,18].…”

Section: Introductionmentioning

confidence: 98%

Cerebral Ischemia is Associated With Corneal Nerve Loss and Brain Atrophy in Mild Cognitive Impairment and Dementia

Ponirakis¹,

Elsotouhy²,

Hamad³

et al. 2020

Preprint

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BackgroundThe prevalence of cerebral ischemia increases with age and is a risk factor for cognitive impairment and dementia. This study assessed the association of brain ischemic lesions with the severity of neurodegeneration utilizing brain volumetric MRI and corneal confocal microscopy (CCM) in patients with mild cognitive impairment (MCI) and dementia.MethodsSubjects with MCI and dementia without diabetes underwent cognitive screening, CCM, assessment of ischemic lesions and quantitative brain MRI.ResultsOf 63 subjects with MCI (n=44) and dementia (n=19), 11 had no ischemia, 32 had subcortical ischemia and 20 had both cortical and subcortical ischemia. Subjects with MCI and dementia had comparable percentage of cerebral ischemia (P=0.25). Global cognitive function was significantly impaired in subjects with both cortical and subcortical ischemia (P<0.05) but not in those with subcortical ischemia (P=0.10) compared to those without ischemia. Corneal nerve fiber density (CNFD)(P<0.01), branch density (CNBD) (P<0.05) and fiber length (CNFL) (P<0.01) were significantly lower in subjects with both cortical and subcortical ischemia compared to those without ischemia and CNFD (P<0.05), CNBD (P<0.05) and CNFL (P<0.05) were significantly lower in subjects with both cortical and subcortical ischemia compared to those with subcortical ischemia. In subjects with both cortical and subcortical ischemia whole brain (P<0.01) and hippocampal volume (P<0.001) were significantly lower and ventricle volume was higher (P<0.05) compared to those without ischemia and hippocampal volume (P<0.01) was lower and ventricle volume was higher (P<0.01) in subjects with both cortical and subcortical ischemia compared to those with subcortical ischemia.ConclusionsThe presence of cortical and subcortical ischemia is associated with cognitive impairment, corneal nerve loss and brain atrophy in patients with MCI and dementia.

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Association of corneal nerve fiber measures with cognitive function in dementia

Cited by 64 publications

References 44 publications

Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke

Corneal confocal microscopy identifies greater corneal nerve damage in patients with a recurrent compared to first ischemic stroke

Corneal nerve and brain imaging in mild cognitive impairment and dementia: A cross-sectional study

Cerebral Ischemia is Associated With Corneal Nerve Loss and Brain Atrophy in Mild Cognitive Impairment and Dementia

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