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/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.

Association of corneal nerve fiber measures with cognitive function in dementia.

OBJECTIVES: Corneal confocal microscopy (CCM) is a noninvasive ophthalmic technique that identifies corneal nerve degeneration in a range of peripheral neuropathies and in patients with multiple sclerosis, Parkinson's disease, and amyotrophic lateral sclerosis. We sought to determine whether there is any association of corneal nerve fiber measures with cognitive function and functional independence in patients with MCI and dementia. METHODS: In this study, 76 nondiabetic participants with MCI (n = 30), dementia (n = 26), and healthy age-matched controls (n = 20) underwent assessment of cognitive and physical function and CCM. RESULTS: There was a progressive reduction in corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL) (P < 0.0001) in patients with MCI and dementia compared to healthy controls. Adjusted for confounders, all three corneal nerve fiber measures were significantly associated with cognitive function (P < 0.05) and functional independence (P < 0.01) in MCI and dementia. The area under the ROC curve to distinguish MCI with CNFD, CNBD, and CNFL was 69.1%, 73.2%, and 73.0% and for dementia it was 84.8%, 84.2%, and 86.2%, respectively. INTERPRETATION: CCM demonstrates corneal nerve fiber loss, which is associated with a decline in cognitive function and functional independence in patients with MCI and dementia.