Corneal Nerve and Brain Imaging in Mild Cognitive Impairment and Dementia

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/mm(2)) (32.0±7.5 versus 24.5±9.6 and 20.8±9.3, p < 0.0001), branch density (CNBD, branches/mm(2)) (90.9±46.5 versus 59.3±35.7 and 53.9±38.7, p < 0.0001), and fiber length (CNFL, mm/mm(2)) (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.