Characterization of Inner Retinal Hyperreflective Alterations in Early Cognitive Impairment on Adaptive Optics Scanning Laser Ophthalmoscopy

Purpose: To examine inner retinal hyperreflective features on adaptive optics scanning laser ophthalmoscopy (AOSLO) in individuals with early cognitive impairment. Methods: In this prospective, cross-sectional study, we enrolled 12 participants with either amnestic mild cognitive impairment (aMCI, n = 10) or early dementia due to Alzheimer's disease (eAD, n = 2) and 12 age-, sex-, and race-matched cognitively normal controls. All participants completed AOSLO imaging of the inner retina. AOSLO montages of the peripapillary area were graded for hyperreflective features including granular membranes, mottled membranes, and nummular features. Regions of interest on AOSLO were compared qualitatively to corresponding optical coherence tomography (OCT) cross sections. OCT was also used to analyze peripapillary retinal nerve fiber layer (RNFL) thickness. Results: Cognitively impaired individuals had a significantly higher number of granular membranes with a larger overall area compared to controls. The proportion of cognitively impaired individuals with two or more granular membranes was 41.7% compared to none in the control group. Granular membrane area was also inversely correlated with cognitive performance on the Montreal Cognitive Assessment. There was no difference between the two groups in terms of other membrane types or RNFL thickness. Conclusions: Individuals with early cognitive impairment related to Alzheimer's show hyperreflective granular membranes on high-resolution imaging, which we hypothesize to be manifestations of inner retinal gliosis. The presence of these subtle hyperreflective membranes may obscure underlying RNFL thinning in these eyes on OCT imaging. The distinctive phenotype of granular membranes surrounding the optic nerve on AOSLO may represent a new potential biomarker of early Alzheimer's.