Change in retinal structural anatomy during the preclinical stage of Alzheimer's disease

Abstract

Introduction We conducted a 27-month longitudinal study of mid-life adults with preclinical Alzheimer's disease (AD), using spectral domain optical coherence tomography to compare changes in volume and thickness in all retinal neuronal layers to those of age-matched healthy control subjects. Methods Fifty-six older adults (mean age = 65.36 years) with multiple risk factors for AD completed spectral domain optical coherence tomography retinal imaging and cognitive testing at baseline. Twenty-seven months later, they completed the same examinations and an 18 F-florbetapir positron emission tomography imaging study. Results Compared to healthy control subjects, those in the preclinical stage of AD showed a significant decrease in macular retinal nerve fiber layer (mRNFL) volume, over a 27-month follow-up interval period, as well as a decrease in outer nuclear layer and inner plexiform layer volumes and thickness in the inferior quadrant. However, only the mRNFL volume was linearly related to neocortical positron emission tomography amyloid standardized uptake value ratio after controlling for any main effects of age ( R 2 = 0.103; ρ = 0.017). Furthermore, the magnitude of mRNFL volume reduction was significantly correlated with performance on a task of participants' abilities to efficiently integrate visual and auditory speech information (McGurk effect). Discussion We observed a decrease in mRNFL, outer nuclear layer, and inner plexiform layer volumes, in preclinical AD relative to controls. Moreover, the largely myelinated axonal loss in the RNFL is related to increased neocortical amyloid-β accumulation after controlling for age. Volume loss in the RNFL, during the preclinical stage, is not related to performance on measures of episodic memory or problem solving. However, this retinal change does appear to be modestly related to relative decrements in performance on a measure of audiovisual integration efficiency that has been recently advanced as a possible early cognitive marker of mild cognitive impairment.

Retinal layer thickness in preclinical Alzheimer's disease

“…In line with our study, no differences in retinal layer thickness or volume was found in the baseline data of the longitudinal study (Santos et al. ). However, A β positivity was associated with an increased reduction in the macular RNFL, ONL and IPL volume and higher standardized uptake value ratio (SUVr) of A β was associated with increased reduction of macular RNFL during a follow‐up of 27 months.…”

“…; Santos et al. ). The present findings are in contrast with the cross‐sectional study, which reported a larger volume of the inner plexiform layer in individuals positive for A β on PET (Snyder et al.…”

“…; Santos et al. ). The development of a new non‐invasive, patient friendly and easily repeatable measurement of a biomarker for pre‐clinical AD patients is especially interesting, because it would allow for early interventions targeting the causes at a stage that neuronal damage could still be prevented (Sun et al.…”

Association between retinal thickness and β-amyloid brain accumulation in individuals with subjective cognitive decline: Fundació ACE Healthy Brain Initiative

“…Most of these studies reported exclusively crosssectional OCT of the retina data. Resembling our design, Santos et al reported longitudinal OCT of the retina and Aβ-PET data over 27 months [49]. A decrease in macular RNFL volume was demonstrated in the preclinical AD group (n = 15) compared to controls (n = 41) and this change was related to Aβ deposition, while GCL volume change was related to age but not to amyloid burden.…”

Predictive Projection in Color Fundus-Retail Images for Detection of Alzheimer’s disease

“…The metabolic and functional abilities of retina will be reflected by repeated analysis of oxygen saturation in retinal blood vessels. This technique has facilitated detection of numerous diseases due to retinal malfunctions, diabetics, maculopathy and even brain diseases [16]. This enabled the usage of RO technique for detecting AD.…”