1. Retinal nerve fiber layer thickness predicts CSF amyloid/tau before cognitive decline.
- Author
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Asanad S, Fantini M, Sultan W, Nassisi M, Felix CM, Wu J, Karanjia R, Ross-Cisneros FN, Sagare AP, Zlokovic BV, Chui HC, Pogoda JM, Arakaki X, Fonteh AN, Sadun AA, and Harrington MG
- Subjects
- Aged, Aged, 80 and over, Alzheimer Disease cerebrospinal fluid, Alzheimer Disease diagnostic imaging, Alzheimer Disease pathology, Amyloid beta-Peptides cerebrospinal fluid, Amyloidosis cerebrospinal fluid, Amyloidosis diagnostic imaging, Amyloidosis genetics, Amyloidosis pathology, Biomarkers cerebrospinal fluid, Cognitive Dysfunction cerebrospinal fluid, Cognitive Dysfunction diagnostic imaging, Cognitive Dysfunction pathology, Female, Humans, Male, Middle Aged, Nerve Fibers metabolism, Nerve Fibers pathology, Optic Disk diagnostic imaging, Optic Disk metabolism, Optic Disk pathology, Retina diagnostic imaging, Retina metabolism, Retina pathology, Retinal Ganglion Cells metabolism, Retinal Ganglion Cells pathology, Tomography, Optical Coherence, tau Proteins cerebrospinal fluid, Alzheimer Disease genetics, Amyloid beta-Peptides genetics, Cognitive Dysfunction genetics, tau Proteins genetics
- Abstract
Background: Alzheimer's disease (AD) pathology precedes symptoms and its detection can identify at-risk individuals who may benefit from early treatment. Since the retinal nerve fiber layer (RNFL) is depleted in established AD, we tested whether its thickness can predict whether cognitively healthy (CH) individuals have a normal or pathological cerebrospinal fluid (CSF) Aß42 (A) and tau (T) ratio., Methods: As part of an ongoing longitudinal study, we enrolled CH individuals, excluding those with cognitive impairment and significant ocular pathology. We classified the CH group into two sub-groups, normal (CH-NAT, n = 16) or pathological (CH-PAT, n = 27), using a logistic regression model from the CSF AT ratio that identified >85% of patients with a clinically probable AD diagnosis. Spectral-domain optical coherence tomography (OCT) was acquired for RNFL, ganglion cell-inner plexiform layer (GC-IPL), and macular thickness. Group differences were tested using mixed model repeated measures and a classification model derived using multiple logistic regression., Results: Mean age (± standard deviation) in the CH-PAT group (n = 27; 75.2 ± 8.4 years) was similar (p = 0.50) to the CH-NAT group (n = 16; 74.1 ± 7.9 years). Mean RNFL (standard error) was thinner in the CH-PAT group by 9.8 (2.7) μm; p < 0.001. RNFL thickness classified CH-NAT vs. CH-PAT with 87% sensitivity and 56.3% specificity., Conclusions: Our retinal data predict which individuals have CSF biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity. Such results from easy-to-acquire, objective and non-invasive measurements of the RNFL merit further study of OCT technology to monitor or screen for early AD pathology., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
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