Relationship of structural and functional visual biomarkers with measures of amyloid, tau, and neurodegeneration across the AD continuum

Abstract

AbstractBackgroundThe eye often reflects changes seen in the brain in neurodegenerative diseases. This study sought to examine the relationship of contrast sensitivity measured using frequency doubling technology (FDT) and retinal thickness measured using optical coherence tomography (OCT) with temporal lobe neurodegeneration, cerebral tau deposition, and mean plasma ptau181 in older adults along the Alzheimer’s disease (AD) continuum.MethodParticipants included 28 individuals with subjective cognitive decline (SCD), 18 mild cognitive impairment (MCI), 4 with AD, and 30 age‐matched cognitive normal (CN) from the Indiana Memory and Aging Study at the Indiana ADRC. Participants were excluded from the study if they had significant eye disease determined to interfere with OCT, FDT, non‐AD dementia, or exclusion for MRI or PET. Mean deviation (MD) and pattern standard deviation (PSD) from FDT were used as measures of contrast sensitivity. OCT scans from each eye to measure retinal thickness in the retinal nerve fiber layer (RNFL) and macula. MRI scans were processed using Freesurfer v6 to measure medial (MTL) and lateral temporal lobe (LTL) volumes. LTL SUVR values were extracted from [18F]flortaucipir PET scans. Plasma ptau 181 was measured using a SIMOA assay. Finally, the association between contrast sensitivity, average RNFL thickness, macular volumes with temporal lobe volumes, LTL tau, and mean plasma ptau181 was assessed using a partial Pearson correlation, covaried for age, sex, and diagnosis. p<0.05 was considered significant.ResultRNFL thickness was decreased in patients with AD. Hippocampal volume correlated with RNFL thickness and macular volume in both eyes and with PSD in the left eye. The inferior temporal volume correlated with MD in both eyes, while mean plasma ptau181 with PSD in both eyes. Finally, lateral temporal lobe tau was correlated with the inner retinal layers of ganglion cell layer plus inner plexiform layer thickness.ConclusionContrast sensitivity correlates with temporal lobe volumes and mean plasma ptau181. RNFL thinning and macular volumes are associated with hippocampal atrophy, and inner retinal nuclear layers correlate with lateral temporal tau. Imaging of the eye may represent a useful biomarker to screen patients at risk for AD prior to more invasive and prolonged testing.