Abstract
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. 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. 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. 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.
Highlights
Alzheimer’s disease (AD) is the leading cause of dementia and one of the most expensive diseases in America at a total cost of $290 billion in 2019 [1,2,3]
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
Our retinal data predict which individuals have cerebrospinal fluid (CSF) biomarkers of AD pathology before cognitive deficits are detectable with 87% sensitivity
Summary
Alzheimer’s disease (AD) is the leading cause of dementia and one of the most expensive diseases in America at a total cost of $290 billion in 2019 [1,2,3]. In considering accessible and noninvasive screening approaches, ophthalmologic impairments including contrast sensitivity, color recognition, and motion perception have been reported in early stages of dementia, even prior to manifesting as a clear diagnosis of AD [6,7,8,9,10,11,12] These visual dysfunctions in AD have been associated with degeneration of the optic nerve and retina, developmental outgrowths of the brain [13,14,15], since cortical deficits alone do not explain these visual deficits [11,12,16,17]. 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
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