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Abstract 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

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., Competing Interests: The authors confirm that the manuscript has been read and approved by all named authors and that there are no other persons who satisfied the criteria for authorship and are not listed. They also confirm that the order of authors listed in the manuscript has been approved by all authors. Dr. Surjith Vattoth has Elsevier book author royalty, received consulting fee as an Elsevier master author consultant in head and neck imaging, and received payment for ESNR ‐ ECHNR course faculty. None of the other authors have received or anticipate receiving income, goods, or benefit from a company that will influence the design, conduct, or reporting of the study., (© 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.)