Abstract

PURPOSE: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.

METHODS: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BPND ) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ- individuals and associations between BPND and retinal thickness were analyzed.

RESULTS: No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ- individuals. A positive associations between BPND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068).

CONCLUSION: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.

Original languageEnglish
JournalActa Ophthalmologica
DOIs
Publication statusE-pub ahead of print - 6 May 2019

Cite this

@article{24aea457bd074c88ae86d85051211d4d,
title = "Retinal layer thickness in preclinical Alzheimer's disease",
abstract = "PURPOSE: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.METHODS: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BPND ) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ- individuals and associations between BPND and retinal thickness were analyzed.RESULTS: No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ- individuals. A positive associations between BPND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068).CONCLUSION: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.",
author = "{van de Kreeke}, {Jacoba A} and Hoang-Ton Nguyen and {den Haan}, Jurre and Elles Konijnenberg and Jori Tomassen and {den Braber}, Anouk and {Ten Kate}, Mara and Lyduine Collij and Maqsood Yaqub and {van Berckel}, Bart and Lammertsma, {Adriaan A} and Boomsma, {Dorret I} and Tan, {Hendra Stevie} and Verbraak, {Frank D} and Visser, {Pieter Jelle}",
note = "{\circledC} 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.",
year = "2019",
month = "5",
day = "6",
doi = "10.1111/aos.14121",
language = "English",
journal = "Acta Ophthalmologica",
issn = "1755-375X",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Retinal layer thickness in preclinical Alzheimer's disease

AU - van de Kreeke, Jacoba A

AU - Nguyen, Hoang-Ton

AU - den Haan, Jurre

AU - Konijnenberg, Elles

AU - Tomassen, Jori

AU - den Braber, Anouk

AU - Ten Kate, Mara

AU - Collij, Lyduine

AU - Yaqub, Maqsood

AU - van Berckel, Bart

AU - Lammertsma, Adriaan A

AU - Boomsma, Dorret I

AU - Tan, Hendra Stevie

AU - Verbraak, Frank D

AU - Visser, Pieter Jelle

N1 - © 2019 Acta Ophthalmologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

PY - 2019/5/6

Y1 - 2019/5/6

N2 - PURPOSE: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.METHODS: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BPND ) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ- individuals and associations between BPND and retinal thickness were analyzed.RESULTS: No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ- individuals. A positive associations between BPND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068).CONCLUSION: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.

AB - PURPOSE: There is urgent need for non-invasive diagnostic biomarkers in the preclinical phase of Alzheimer's Disease (AD). Several studies suggest that retinal thickness is reduced in AD. Here, we aim to test the diagnostic value of retinal thickness in preclinical AD, as defined by cognitively normal individuals with amyloid pathology on PET.METHODS: One hundred and sixty five cognitively healthy monozygotic twins aged ≥ 60 were included from the Netherlands Twin Register taking part in the European Medical Information Framework for Alzheimer's Disease PreclinAD study. Participants underwent [18 F] flutemetamol PET that was visually rated for presence or absence of cortical amyloid beta (Aβ). Binding potential (BPND ) was calculated as continuous measure for Aβ. Spectral Domain OCT was used to asses total and individual inner retinal layer thickness in the macular region (ETDRS circles) as well as peripapillary retinal nerve fibre layer (pRNFL) thickness. Differences between Aβ+ and Aβ- individuals and associations between BPND and retinal thickness were analyzed.RESULTS: No differences were found in retinal layer thickness in the macula or pRNFL between Aβ+ and Aβ- individuals. A positive associations between BPND and macular total retinal thickness was observed in the inner ring (p = 0.018), but this was not statistically significant after correction for multiple testing (p = 0.144). Brain/eye parameters had moderate to high intra-twin correlations (p < 0.001) except visual rating score of Aβ, which did not correlate (r = 0.21, p = 0.068).CONCLUSION: Variation in retinal thickness likely reflects genetic differences between individuals, but cannot discriminate between healthy and preclinical AD cases, making its use as biomarker in these early stages limited.

U2 - 10.1111/aos.14121

DO - 10.1111/aos.14121

M3 - Article

JO - Acta Ophthalmologica

JF - Acta Ophthalmologica

SN - 1755-375X

ER -