Retinal layer thickness in preclinical Alzheimer's disease.
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.
['van de Kreeke|Jacoba A|JA|https://orcid.org/0000-0002-0165-1839', 'Nguyen|Hoang-Ton|HT|', 'den Haan|Jurre|J|https://orcid.org/0000-0003-1476-5568', 'Konijnenberg|Elles|E|', 'Tomassen|Jori|J|', 'den Braber|Anouk|A|', 'Ten Kate|Mara|M|', 'Collij|Lyduine|L|', 'Yaqub|Maqsood|M|', 'van Berckel|Bart|B|', 'Lammertsma|Adriaan A|AA|', 'Boomsma|Dorret I|DI|', 'Tan|Hendra Stevie|HS|', 'Verbraak|Frank D|FD|', 'Visser|Pieter Jelle|PJ|']
D000368:Aged D000544:Alzheimer Disease D001921:Brain D005260:Female D006801:Humans D008266:Macula Lutea D008279:Magnetic Resonance Imaging D008297:Male D008875:Middle Aged D012165:Retinal Ganglion Cells D041623:Tomography, Optical Coherence
preclinical Alzheimer's disease twins OCT ocular biomarkers retina