Retinal optical coherence tomography (OCT) measurements may be associated with genetic Alzheimer’s disease risk
1. In a retrospective study examining 50,000 optical coherence tomography (OCT) images from a large database, thicknesses of several different retinal layers were significantly associated with Alzheimer’s disease and Parkinson’s disease polygenic risk scores.
2. Higher baseline thickness of two specific retinal layers was also significantly associated with poorer clinical cognitive performance in the future.
Evidence Rating Level: 2 (Good)
Study Rundown: Optical coherence tomography (OCT) is an imaging modality that can be used to visualize and measure the posterior segment of the eye, including the retina. OCT retinal metrics, which may indicate differences in vascularity and perfusion, have been flagged as a possible marker for neurodegenerative disease, including Alzheimer’s. This cohort study aimed to correlate OCT measurements with genetic risk for Alzheimer’s and Parkinson’s disease to assess and compare the performance of these eye metrics with polygenic risk scores (PRS). Among about 52,000 subjects, thicker inner nuclear layer, chorioscleral interface, and photoreceptor layer on OCT were significantly associated with higher PRS for Alzheimer’s disease after adjustment for demographic factors. Higher Parkinson’s disease PRS was significantly associated with thinner outer plexiform layer and chorioscleral interface. A regression model combining OCT with PRS data better predicted decline in cognitive function scores than demographic factors in the subset of patients with follow-up cognitive assessment. Overall, retinal layer thicknesses on OCT correlated with PRS in both Alzheimer’s and Parkinson’s. Models including OCT data had modest but significant predictive value. This study is consistent with past findings correlating thinner retinal nerve fiber layer with risk for cognitive decline. OCT has potential for noninvasive early detection of cognitive disease and refinement of clinical surveillance protocols, although coordination of care between eye specialists and other providers presents a potential challenge.
Click to read the study in BJO
Relevant Reading: Retinal imaging in Alzheimer’s disease
In-Depth [retrospective cohort]: Study data were drawn from the UK Biobank, a large data set including demographic and genotype data along with diagnostic codes, which were used to identify patients with Alzheimer’s disease and Parkinson’s disease. For about 7,500 patients, follow-up cognitive assessment was performed an average of 4 years later. Patients with glaucoma and age-related macular degeneration were excluded. PRS were calculated based on variants identified in past genome-wide association studies for both Alzheimer’s and Parkinson’s. PRS for the respective diseases were significantly higher in patients diagnosed with Alzheimer’s and Parkinson’s, respectively, than in controls. Spectral-domain macular OCT images were analyzed using native segmentation algorithms to measure retinal layer thicknesses. Regression models were used to calculate correlation between PRS and OCT metrics with adjustment for age, sex, ancestry, hypertension, diabetes, dyslipidemia, and cardiovascular disease status. Thicknesses of several other retinal layers were associated with risk for baseline cognitive deficits and with cognitive decline. The area under the curve for the model including OCT and PRS data was 0.659 as compared to 0.656 for a demographic model.
Image: PD
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