Corneal nerve fiber measures independently predict progression from MCI to dementia: Follow‐up of the Qatar Longitudinal Study Cohort

Abstract

AbstractBackgroundThere is an urgent need for biomarkers of neurodegeneration to identify individuals with MCI at higher risk for developing dementia. Corneal confocal microscopy (CCM) is a non‐invasive imaging biomarker which has identified corneal nerve loss in individuals with mild cognitive impairment (MCI) and dementia. This study assessed the predictive capability of CCM and MRI brain volumetry for progression from participants with MCI to dementia.MethodIn this prospective study, participants aged 50‐85 with MCI underwent assessment of clinical dementia rating (CDR), Montreal cognitive assessment (MoCA), MRI brain volumetry and CCM at baseline and CDR and MoCA at 1‐4 year follow‐up.ResultThe study cohort comprised 107 participants with MCI aged 68.4±7.7 years. Over a median follow‐up of 2.4 years, 33 of 107 participants (30.8%) with MCI progressed to dementia. Corneal nerve fibre density (P<0.0001), branch density (P<0.0001) and length (P<0.0001) were significantly lower in MCI participants who progressed to dementia. Reduced baseline corneal nerve fiber density (≤25 fiber/mm2), length (≤15 mm/mm2) and branch density (≤44 branches/mm2) accurately predicted future dementia (area under the curve (AUC) = 71‐74%, P≤0.0001). Reduced baseline intra‐cranial volume percentage (ICV %), hippocampus (≤0.44%), whole brain (≤69.4%), frontal lobe (≤10.8%), amygdala (≤0.17%), cortical gray matter (≤29%), thalamus (≤0.90%) and increased ventricle (≥3.0%) volume predicted future dementia (AUC = 65‐78%, P<0.05), whilst temporal, parietal, occipital lobe, entorhinal cortex, cingulate gyrus and brainstem did not. The adjusted odds ratios (AOR) for progression to dementia were 5.1‐11.1 times higher with abnormal corneal nerve fiber measures (P<0.05), 5.9 higher with abnormal hippocampal volume (P<0.05) and 10.8 times higher with whole‐brain volume (P<0.05).ConclusionThe predictive capability of CCM is comparable to hippocampal and whole brain volume for progression to dementia in individuals with MCI.