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

Abstract 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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Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia

Journal of Alzheimer s Disease ◽

10.3233/jad-200678 ◽

2020 ◽

Vol 77 (4) ◽

pp. 1533-1543

Author(s):

Eiman Al-Janahi ◽

Georgios Ponirakis ◽

Hanadi Al Hamad ◽

Surjith Vattoth ◽

Ahmed Elsotouhy ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Diagnostic Accuracy ◽

Temporal Lobe ◽

Medial Temporal Lobe ◽

Medial Temporal Lobe Atrophy ◽

Non Invasive ◽

Corneal Confocal Microscopy ◽

Corneal Nerve ◽

Lobe Atrophy

Background: Visual rating of medial temporal lobe atrophy (MTA) is an accepted structural neuroimaging marker of Alzheimer’s disease. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic technique that detects neuronal loss in peripheral and central neurodegenerative disorders. Objective: To determine the diagnostic accuracy of CCM for mild cognitive impairment (MCI) and dementia compared to medial temporal lobe atrophy (MTA) rating on MRI. Methods: Subjects aged 60–85 with no cognitive impairment (NCI), MCI, and dementia based on the ICD-10 criteria were recruited. Subjects underwent cognitive screening, CCM, and MTA rating on MRI. 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 mixed AD (n = 34, 51.5%) were studied. CCM showed a progressive reduction in corneal nerve fiber density (CNFD, fibers/mm2) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm2) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm2) (22.9±6.1 versus 17.2±6.5 and 15.8±7.4, p < 0.0001) in subjects with MCI and dementia compared to NCI. The area under the ROC curve (95% CI) for the diagnostic accuracy of CNFD, CNBD, CNFL compared to MTA-right and MTA-left for MCI was 78% (67–90%), 82% (72–92%), 86% (77–95%) versus 53% (36–69%) and 40% (25–55%), respectively, and for dementia it was 85% (76–94%), 84% (75–93%), 85% (76–94%) versus 86% (76–96%) and 82% (72–92%), respectively. Conclusion: The diagnostic accuracy of CCM, a non-invasive ophthalmic biomarker of neurodegeneration, was high and comparable with MTA rating for dementia but was superior to MTA rating for MCI.

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

10.21203/rs.3.rs-101841/v1 ◽

2020 ◽

Author(s):

Georgios Ponirakis ◽

Ahmed Elsotouhy ◽

Hanadi Al Hamad ◽

Surjith Vattoth ◽

Ioannis N. Petropoulos ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cerebral Ischemia ◽

Brain Atrophy ◽

Hippocampal Volume ◽

Cognitive Screening ◽

Fiber Density ◽

Corneal Confocal Microscopy ◽

Corneal Nerve ◽

Ventricle Volume

Abstract 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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Olfactory Measures as Predictors of Conversion to Mild Cognitive Impairment and Alzheimer’s Disease

Brain Sciences ◽

10.3390/brainsci11111391 ◽

2021 ◽

Vol 11 (11) ◽

pp. 1391

Author(s):

Paul Loyd Wheeler ◽

Claire Murphy

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Roc Curve ◽

Disease Risk ◽

Characteristic Curve ◽

Odor Identification ◽

Non Invasive ◽

Prodromal Alzheimer’S Disease

Background: Early biomarkers of prodromal Alzheimer’s disease (AD) are critical both to initiate interventions and to choose participants for clinical trials. Odor threshold, odor identification and odor familiarity are impaired in AD. Methods: We investigated the relative abilities of standard screening (MMSE) and olfactory measures to predict transitions from cognitively normal (CN) to mild cognitive impairment (MCI), from CN to AD, and MCI to AD. The archival sample of 497, from the UCSD ADRC, included participants who were CN, MCI, AD and converters to MCI or AD. Apoe ε4 status, a genetic risk factor, was available for 256 participants, 132 were ε4 carriers. A receiver operating characteristic curve (ROC) curve plots the trade-off between sensitivity and specificity. Area under the ROC curve (AUC) was used to determine diagnostic accuracy. Results: Different measures were better predictors at specific stages of disease risk; e.g., odor familiarity, odor identification and the combination showed higher predictive value for converting from MCI to AD in ε4 carriers than the MMSE. Combining odor familiarity and odor identification produced an AUC of 1.0 in ε4 carriers, MMSE alone was 0.58. Conclusions: Olfactory biomarkers show real promise as non-invasive indicators of prodromal AD. The results support the value of combining olfactory measures in assessment of risk for conversion to MCI and to AD.

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