The retinal ganglion cell layer reflects neurodegenerative changes in cognitively unimpaired individuals

Abstract

Background To evaluate a wide range of optical coherence tomography (OCT) parameters for possible application as a screening tool for cognitively healthy individuals at risk of Alzheimer’s disease (AD), assessing the potential relationship with established cerebrospinal fluid (CSF) core AD biomarkers and magnetic resonance imaging (MRI). Methods We studied 99 participants from the Valdecilla Study for Memory and Brain Aging. This is a prospective cohort for multimodal biomarker discovery and validation that includes participants older than 55 years without dementia. Participants received a comprehensive neuropsychological battery and underwent structural 3-T brain MRI, lumbar puncture for CSF biomarkers (phosphorylated-181-Tau (pTau), total Tau (tTau), beta-amyloid 1–42 (Aβ 1–42), and beta-amyloid 1–40 (Aβ 1–40)). All individuals underwent OCT to measure the retinal ganglion cell layer (GCL), the retinal nerve fiber layer (RFNL), the Bruch’s membrane opening-minimum rim width (BMO-MRW), and choroidal thickness (CT). In the first stage, we performed a univariate analysis, using Student’s t-test. In the second stage, we performed a multivariate analysis including only those OCT parameters that discriminated at a nominal level, between positive/negative biomarkers in stage 1. Results We found significant differences between the OCT measurements of pTau- and tTau-positive individuals compared with those who were negative for these markers, most notably that the GCL and the RNFL were thinner in the former. In stage 2, our dependent variables were the quantitative values of CSF markers and the hippocampal volume. The Aβ 1–42/40 ratio did not show a significant correlation with OCT measurements while the associations between pTau and tTau with GCL were statistically significant, especially in the temporal region of the macula. Besides, the multivariate analysis showed a significant correlation between hippocampal volume with GCL and RNFL. However, after false discovery rate correction, only the associations with hippocampal volume remained significant. Conclusions We found a significant correlation between Tau (pTau) and neurodegeneration biomarkers (tTau and hippocampus volume) with GCL degeneration and, to a lesser degree, with damage in RFNL. OCT analysis constitutes a non-invasive and unexpensive biomarker that allows the detection of neurodegeneration in cognitively asymptomatic individuals.

Associations between thinner retinal neuronal layers and suboptimal brain structural integrity: Are the eyes a window to the brain?

“…An increasing number of studies have investigated whether retinal neuronal measurements are associated with brain measurements at various stages of AD. The findings are inconsistent, with some studies finding an association between retinal and brain measurements (Jorge et al, 2020; López-de-Eguileta et al, 2022; Mauschitz et al, 2022; Mejia-Vergara et al, 2021; Méndez-Gómez et al, 2018; Mutlu et al, 2018, 2017; Shi et al, 2020, 2019; Uchida et al, 2020), some finding no association (Casaletto et al, 2017; den Haan et al, 2019), and others with inconclusive results (Donix et al, 2021). However, methodological differences may explain some of this inconsistency—systematic differences between OCT or MRI devices across manufacturers and models, choice of parameters and settings, and the wide range of measurements which can be acquired from each of these technologies make comparison across studies difficult.…”

“…Recent studies have investigated these associations in cognitively unimpaired individuals, finding associations between retinal layers including the RNFL and GC-IPL and a number of structural brain measures, most commonly hippocampal volume (Chua et al, 2021; López-de-Eguileta et al, 2022; Shi et al, 2020), but also the lingual gyrus (Shi et al, 2020) and grey and white matter volumes (Chua et al, 2021). A recent study found correlations between RNFL, GC-IPL, and other retinal thickness measures with a large number of cortical thicknesses and volumes, in participants both with and without increased familial and genetic risk for AD (López-Cuenca et al, 2022).…”

Plasma p-tau231 increases at one-year intervals in cognitively unimpaired subjects

“…We conducted this analysis with volunteers of the 'Valdecilla Cohort for the study of memory and brain aging' from the Memory Unit of the Marqués de Valdecilla University Hospital [10,11]. The Valdecilla cohort is designed to better understand the preclinical phases of AD.…”

Associations Between Thinner Retinal Neuronal Layers and Suboptimal Brain Structural Integrity in a Middle-Aged Cohort

“…Recent studies have investigated these associations in cognitively unimpaired individuals, finding associations between retinal layers including the RNFL and GC-IPL and a number of structural brain measures, most commonly hippocampal volume, 21,32,33 but also the lingual gyrus 33 and grey and white matter volumes. 21 A recent study found correlations between RNFL, GC-IPL, and other retinal thickness measures with a large number of cortical thicknesses and volumes, in participants both with and without increased familial and genetic risk for AD.…”