Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline

Abstract

Background: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio.

Methods: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression.

Results: Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) μm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity.

Conclusions: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology.

Fig 1. Illustrates optical coherence tomography imaging of the peripapillary and macular areas.

(A) The thicknesses of the 4 retinal nerve fiber layer quadrants (temporal, superior, nasal, inferior); (B) ganglion cell-inner plexiform layer sectors (superior-temporal, superior, superior-nasal, inferior-nasal, inferior, inferior-temporal; (C) macular full-thickness sectors (center, inner-superior, outer-superior, inner-inferior, outer-inferior, inner-temporal, outer-temporal, inner-nasal, outer-nasal) were measured using peripapillary and macular circular scans centered on the disc and on the fovea, respectively).

Fig 2

Depicts least-squares mean (95% CI) retinal nerve fiber layer (RNFL) thickness adjusted for side and region between cognitively healthy controls (blue) and preclinical AD participants (red).