Abstract
BackgroundRetinal thickness can be measured non-invasively with optical coherence tomography (OCT) and may offer compelling potential as a biomarker for Alzheimer’s disease (AD). Retinal thinning is hypothesized to be a result of retrograde atrophy and/or parallel neurodegenerative processes. Changes in the visual pathway are of particular interest in posterior cortical atrophy (PCA), the most common atypical AD phenotype predominantly affecting the parietal-occipital cortices. We therefore evaluated retinal thickness as non-invasive biomarker of neurodegeneration in well-characterized participants with posterior cortical atrophy (PCA) and typical Alzheimer’s disease (tAD).MethodsRetinal thickness measures were acquired from 48 patient participants (N = 25 PCA; N = 23 tAD) fulfilling consensus diagnostic criteria and 70 age-matched controls. Participants were recruited between 2014 and 2016. All participants underwent optical coherence tomography (OCT) imaging, including measurement of peripapillary retinal nerve fiber layer (pRNFL) thickness and total macular thickness (mRT). Participants did not show evidence of any significant ophthalmological conditions. Subgroup analyses were performed in participants with available MRI and CSF measures, providing evidence of neurodegeneration and underlying AD pathology respectively.ResultsThere was no evidence of overall between-group differences in pRNFL thickness (mean PCA 98.7 ± 12.2; tAD 99.9 ± 8.7; controls 99.6 ± 10.0 μm, one-way analysis of variance (ANOVA) p = 0.92) or total mRT (mean PCA 266.9 ± 16.3; tAD 267.8 ± 13.6; controls 269.3 ± 13.6 μm, one-way ANOVA p = 0.75). Similarly, subgroup analysis with MRI biomarkers (PCA = 18, tAD = 17, controls = 31) showing neurodegeneration, and CSF biomarkers (PCA = 18, tAD = 14, controls = 13) supporting underlying AD pathology did not provide evidence of overall between-group differences in pRNFL or mRT measures (all p > 0.3).ConclusionsRetinal thickness did not discriminate tAD and PCA from controls or from one another despite unequivocal differences on standard clinical, neuro-imaging and CSF measures. Findings from this well-characterized sample, including cases with PCA, do not support the hypothesis that retinal neurodegeneration, measured using conventional OCT, is a useful biomarker for AD or PCA.
Highlights
There is an urgent need for non-invasive Alzheimer’s disease (AD) biomarkers
Regression analyses adjusting for age and gender did not find evidence that patient and control groups differed on peripapillary retinal nerve fiber layer (pRNFL) or macular retinal thickness (mRT) measures (Table 1)
Retinal thickness does not discriminate between groups in Magnetic resonance imaging (MRI) and Cerebrospinal fluid (CSF) sub cohorts Table 1 shows comparisons of cortical thickness, subcortical volumes and CSF measures between posterior cortical atrophy (PCA), typical Alzheimer’s disease (tAD) and control groups
Summary
There is an urgent need for non-invasive Alzheimer’s disease (AD) biomarkers. The retina, sharing its embryological origin with the brain, may reflect AD hallmark pathology [1, 2]. Retinal thinning has been proposed as a promising non-invasive imaging biomarker, purportedly mirroring cortical atrophy owing to trans-synaptic retrograde neurodegeneration, and/or reflecting parallel processes in both retinal and cortical neurons [8]. Retinal thinning is of particular interest in posterior cortical atrophy (PCA), the canonical ‘visual dementia’, and the most common atypical presentation of AD [10]. Retinal thickness can be measured non-invasively with optical coherence tomography (OCT) and may offer compelling potential as a biomarker for Alzheimer’s disease (AD). Changes in the visual pathway are of particular interest in posterior cortical atrophy (PCA), the most common atypical AD phenotype predominantly affecting the parietal-occipital cortices. We evaluated retinal thickness as non-invasive biomarker of neurodegeneration in well-characterized participants with posterior cortical atrophy (PCA) and typical Alzheimer’s disease (tAD)
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