Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia

Ponirakis, Georgios; Elsotouhy, Ahmed; Hamad, Hanadi Al; Vattoth, Surjith; Petropoulos, Ioannis N.; Khan, Adnan; Gad, Hoda; Al‐Khayat, Fatima; Chandran, Mani; Ramadan, Marwan; Elorrabi, Marwa; Gadelseed, Masharig; Tosino, Rhia; Gawhale, Priya V; Alobaidi, Maryam; Khan, Shafi; Manikoth, Pravija; Abdelrahim, Yasmin H M; Thodi, Noushad; Almuhannadi, Hamad; Al-Mohannadi, Salma; AlMarri, Fatema; Qazi, Murtaza; Own, Ahmed; Mahfoud, Ziyad; Shuaib, Ashfaq; Malik, Rayaz A.

doi:10.3389/fnins.2021.690896

Cited by 8 publications

(15 citation statements)

References 34 publications

(52 reference statements)

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“… 43 Corneal nerve loss has also been associated with many of the risk factors for MCI and dementia including hyperglycemia, hypertension and hyperlipidemia, 21 and the presence of white matter hyperintensities, 44 and cerebral ischemia. 45 Although diabetes is associated with corneal nerve loss, 17 , 46 , 47 , 48 , 49 this study shows that the loss of corneal nerve fibers in patients with MCI and dementia remained significant after excluding those with diabetes. Indeed, in our recent study in which diabetes was excluded, there was evidence of significant corneal nerve fiber loss in patients with MCI and dementia.…”

Section: Discussionmentioning

confidence: 71%

“…Tauopathy is a key feature of dementia, 42 and we have recently shown stromal corneal nerve loss in transgenic mice overexpressing human tau 43 . Corneal nerve loss has also been associated with many of the risk factors for MCI and dementia including hyperglycemia, hypertension and hyperlipidemia, 21 and the presence of white matter hyperintensities, 44 and cerebral ischemia 45 . Although diabetes is associated with corneal nerve loss, 17,46–49 this study shows that the loss of corneal nerve fibers in patients with MCI and dementia remained significant after excluding those with diabetes.…”

Section: Discussionmentioning

confidence: 94%

“…The association between neurodegeneration and cognitive function in dementia is complex, as some post‐mortem studies have shown that there are cases of dementia with limited neurodegeneration and equally there are patients with neurodegeneration without cognitive impairment. 52 , 53 , 54 The association between neurodegeneration and cognitive impairment may also be influenced by cerebrovascular ischemia, 45 , 55 which reduces the brain reserve to tolerate neurodegeneration. 54 , 56 The association of corneal nerve loss with cognitive impairment may be influenced by diabetes, as it increases the odds of cerebral ischemia, infarct, and lacunes, 57 which increase the risk of cognitive impairment 58 and dementia.…”

Section: Discussionmentioning

confidence: 99%

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Loss of corneal nerves and brain volume in mild cognitive impairment and dementia

Ponirakis

Hamad

Khan

et al. 2022

A&D Transl Res & Clin Interv

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Introduction This study compared the capability of corneal confocal microscopy (CCM) with magnetic resonance imaging (MRI) brain volumetry for the diagnosis of mild cognitive impairment (MCI) and dementia. Methods In this cross‐sectional study, participants with no cognitive impairment (NCI), MCI, and dementia underwent assessment of Montreal Cognitive Assessment (MoCA), MRI brain volumetry, and CCM. Results Two hundred eight participants with NCI (n = 42), MCI (n = 98), and dementia (n = 68) of comparable age and gender were studied. For MCI, the area under the curve (AUC) of CCM (76% to 81%), was higher than brain volumetry (52% to 70%). For dementia, the AUC of CCM (77% to 85%), was comparable to brain volumetry (69% to 93%). Corneal nerve fiber density, length, branch density, whole brain, hippocampus, cortical gray matter, thalamus, amygdala, and ventricle volumes were associated with cognitive impairment after adjustment for confounders (All P ’s < .01). Discussion The diagnostic capability of CCM compared to brain volumetry is higher for identifying MCI and comparable for dementia, and abnormalities in both modalities are associated with cognitive impairment.

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

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Loss of corneal nerves and brain volume in mild cognitive impairment and dementia

Ponirakis

Hamad

Khan

et al. 2022

A&D Transl Res & Clin Interv

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“…We have pioneered the rapid noninvasive technique of corneal confocal microscopy (CCM) to demonstrate corneal nerve fiber loss in a number of central 14 – 18 and peripheral 19 – 22 neurodegenerative diseases and increased Langerhans cells (LCs) in inflammatory and immune-mediated neuropathies 23 – 27 and long-coronavirus disease (COVID). 28 Moreover, we have shown that CCM has equivalent diagnostic utility to quantitative sensory testing and enhances the diagnosis of small fiber neuropathy.…”

Section: Introductionmentioning

confidence: 99%

Subclinical Corneal Nerve Fiber Damage and Immune Cell Activation in Systemic Lupus Erythematosus: A Corneal Confocal Microscopy Study

Bitirgen

Küçük

Ergun

et al. 2021

Trans. Vis. Sci. Tech.

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Purpose The purpose of this study was to evaluate the utility of corneal confocal microscopy (CCM) in identifying small nerve fiber damage and immune cell activation in patients with systemic lupus erythematosus (SLE). Methods This cross-sectional comparative study included 39 consecutive patients with SLE and 30 healthy control participants. Central corneal sensitivity was assessed using a Cochet-Bonnet contact corneal esthesiometer and a laser scanning CCM (Heidelberg, Germany) was used to quantify corneal nerve fiber density (CNFD), nerve branch density (CNBD), nerve fiber length (CNFL), and Langerhans cell (LC) density. Results Age was comparable among patients with SLE (33.7 ± 12.7) and controls (35.0 ± 13.7 years, P = 0.670) and the median duration of disease was 3.0 years (2.0–10.0 years). CNBD ( P = 0.003) and CNFL ( P = 0.019) were lower and mature LC density ( P = 0.002) was higher, but corneal sensitivity ( P = 0.178) and CNFD ( P = 0.198) were comparable in patients with SLE compared with controls. The SELENA-SLEDAI score correlated with CNFD (ρ = −0.319, P = 0.048) and CNFL (ρ = −0.373, P = 0.019), and the total and immature LC densities correlated with CNBD (ρ = −0.319. P = 0.048, and ρ = −0.328, P = 0.041, respectively). Immature LC density was higher ( P = 0.025), but corneal sensitivity and nerve fiber parameters were comparable between patients with (33%) and without neuropsychiatric symptoms and SLE. Conclusions Corneal confocal microscopy identifies distal corneal nerve fiber loss and increased immune cell density in patients with SLE and corneal nerve loss was associated with disease activity. Translational Relevance Corneal confocal microscopy may enable the detection of subclinical corneal nerve loss and immune cell activation in SLE.

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“…In patients with mild cognitive impairment and dementia, corneal nerve fibre loss is associated with the degree of cognitive impairment and physical disability [ 86 , 87 ]. The severity of cerebral ischemia is associated with cognitive impairment, brain atrophy, and corneal nerve loss in mild cognitive impairment and dementia [ 88 ].…”

Section: Ccm In Central Neurodegenerative Diseasementioning

confidence: 99%

Corneal Confocal Microscopy and the Nervous System: Introduction to the Special Issue

Malik

Efron

2022

JCM

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Association of Cerebral Ischemia With Corneal Nerve Loss and Brain Atrophy in MCI and Dementia

Cited by 8 publications

References 34 publications

Loss of corneal nerves and brain volume in mild cognitive impairment and dementia

Loss of corneal nerves and brain volume in mild cognitive impairment and dementia

Subclinical Corneal Nerve Fiber Damage and Immune Cell Activation in Systemic Lupus Erythematosus: A Corneal Confocal Microscopy Study

Corneal Confocal Microscopy and the Nervous System: Introduction to the Special Issue

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