Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer's disease

Jurre den Haan, Lajos Csinscik, Tom Parker, Ross W. Paterson, Catherine F. Slattery, Alexander Foulkes, Femke H. Bouwman, Frank D. Verbraak, Philip Scheltens, Tunde Peto, Imre Lengyel, Jonathan M. Schott, Sebastian J. Crutch, Timothy J. Shakespeare, Keir X. X. Yong

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

BACKGROUND: 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). 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). METHODS: Retinal 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. RESULTS: There 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). CONCLUSIONS: Retinal 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.
Original languageEnglish
Pages (from-to)62
Number of pages1
JournalAlzheimer's Research & Therapy
Volume11
Issue number1
DOIs
Publication statusPublished - 18 Jul 2019

Cite this

den Haan, Jurre ; Csinscik, Lajos ; Parker, Tom ; Paterson, Ross W. ; Slattery, Catherine F. ; Foulkes, Alexander ; Bouwman, Femke H. ; Verbraak, Frank D. ; Scheltens, Philip ; Peto, Tunde ; Lengyel, Imre ; Schott, Jonathan M. ; Crutch, Sebastian J. ; Shakespeare, Timothy J. ; Yong, Keir X. X. / Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer's disease. In: Alzheimer's Research & Therapy. 2019 ; Vol. 11, No. 1. pp. 62.
@article{9d505deb20104c72b9df098bbdb60f04,
title = "Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer's disease",
abstract = "BACKGROUND: 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). 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). METHODS: Retinal 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. RESULTS: There 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). CONCLUSIONS: Retinal 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.",
keywords = "Alzheimer’s disease, Biomarker, MRI, Optical coherence tomography, Posterior cortical atrophy, Retinal thickness",
author = "{den Haan}, Jurre and Lajos Csinscik and Tom Parker and Paterson, {Ross W.} and Slattery, {Catherine F.} and Alexander Foulkes and Bouwman, {Femke H.} and Verbraak, {Frank D.} and Philip Scheltens and Tunde Peto and Imre Lengyel and Schott, {Jonathan M.} and Crutch, {Sebastian J.} and Shakespeare, {Timothy J.} and Yong, {Keir X. X.}",
year = "2019",
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language = "English",
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pages = "62",
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Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer's disease. / den Haan, Jurre; Csinscik, Lajos; Parker, Tom; Paterson, Ross W.; Slattery, Catherine F.; Foulkes, Alexander; Bouwman, Femke H.; Verbraak, Frank D.; Scheltens, Philip; Peto, Tunde; Lengyel, Imre; Schott, Jonathan M.; Crutch, Sebastian J.; Shakespeare, Timothy J.; Yong, Keir X. X.

In: Alzheimer's Research & Therapy, Vol. 11, No. 1, 18.07.2019, p. 62.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Retinal thickness as potential biomarker in posterior cortical atrophy and typical Alzheimer's disease

AU - den Haan, Jurre

AU - Csinscik, Lajos

AU - Parker, Tom

AU - Paterson, Ross W.

AU - Slattery, Catherine F.

AU - Foulkes, Alexander

AU - Bouwman, Femke H.

AU - Verbraak, Frank D.

AU - Scheltens, Philip

AU - Peto, Tunde

AU - Lengyel, Imre

AU - Schott, Jonathan M.

AU - Crutch, Sebastian J.

AU - Shakespeare, Timothy J.

AU - Yong, Keir X. X.

PY - 2019/7/18

Y1 - 2019/7/18

N2 - BACKGROUND: 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). 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). METHODS: Retinal 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. RESULTS: There 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). CONCLUSIONS: Retinal 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.

AB - BACKGROUND: 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). 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). METHODS: Retinal 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. RESULTS: There 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). CONCLUSIONS: Retinal 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.

KW - Alzheimer’s disease

KW - Biomarker

KW - MRI

KW - Optical coherence tomography

KW - Posterior cortical atrophy

KW - Retinal thickness

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UR - https://www.ncbi.nlm.nih.gov/pubmed/31319885

U2 - 10.1186/s13195-019-0516-x

DO - 10.1186/s13195-019-0516-x

M3 - Article

VL - 11

SP - 62

JO - Alzheimer's Research & Therapy

JF - Alzheimer's Research & Therapy

SN - 1758-9193

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