Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings | Radiology | JAMA Ophthalmology | JAMA Network
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Original Investigation
November 2018

Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings

Author Affiliations
  • 1Department of Ophthalmology and Vision Science, Washington University in St Louis, St Louis, Missouri
  • 2Department of Medicine, Washington University in St Louis, St Louis, Missouri
  • 3Department of Developmental Biology, Washington University in St Louis, St Louis, Missouri
  • 4Blue Sky Neurology, Denver, Colorado
  • 5Division of Biostatistics, Washington University in St Louis, St Louis, Missouri
  • 6Department of Neurology, Washington University in St Louis, St Louis, Missouri
JAMA Ophthalmol. 2018;136(11):1242-1248. doi:10.1001/jamaophthalmol.2018.3556
Key Points

Question  Do study participants with biomarker-positive findings for preclinical Alzheimer disease have retinal microvascular alterations detectable by optical coherence tomographic angiography compared with control individuals with biomarker-negative findings?

Findings  In this single-center, case-control study, the foveal avascular zone was larger in participants with preclinical Alzheimer disease determined by the presence of β-amyloid biomarkers (mean [SD], 0.364 [0.095] mm2) compared with those without preclinical Alzheimer disease (mean [SD], 0.275 [0.060] mm2).

Meaning  Foveal avascular zone enlargement may offer a noninvasive, cost-efficient, and rapid screen to identify preclinical Alzheimer disease.


Importance  Biomarker testing for asymptomatic, preclinical Alzheimer disease (AD) is invasive and expensive. Optical coherence tomographic angiography (OCTA) is a noninvasive technique that allows analysis of retinal and microvascular anatomy, which is altered in early-stage AD.

Objective  To determine whether OCTA can detect early retinal alterations in cognitively normal study participants with preclinical AD diagnosed by criterion standard biomarker testing.

Design, Setting, and Participants  This case-control study included 32 participants recruited from the Charles F. and Joanne Knight Alzheimer Disease Research Center, Washington University in St Louis, St Louis, Missouri. Results of extensive neuropsychometric testing determined that all participants were cognitively normal. Participants underwent positron emission tomography and/or cerebral spinal fluid testing to determine biomarker status. Individuals with prior ophthalmic disease, media opacity, diabetes, or uncontrolled hypertension were excluded. Data were collected from July 1, 2016, through September 30, 2017, and analyzed from July 30, 2016, through December 31, 2017.

Main Outcomes and Measures  Automated measurements of retinal nerve fiber layer thickness, ganglion cell layer thickness, inner and outer foveal thickness, vascular density, macular volume, and foveal avascular zone were collected using an OCTA system from both eyes of all participants. Separate model III analyses of covariance were used to analyze individual data outcome.

Results  Fifty-eight eyes from 30 participants (53% female; mean [SD] age, 74.5 [5.6] years; age range, 62-92 years) were included in the analysis. One participant was African American and 29 were white. Fourteen participants had biomarkers positive for AD and thus a diagnosis of preclinical AD (mean [SD] age, 73.5 [4.7] years); 16 without biomarkers served as a control group (mean [SD] age, 75.4 [6.6] years). The foveal avascular zone was increased in the biomarker-positive group compared with controls (mean [SD], 0.364 [0.095] vs 0.275 [0.060] mm2; P = .002). Mean (SD) inner foveal thickness was decreased in the biomarker-positive group (66.0 [9.9] vs 75.4 [10.6] μm; P = .03).

Conclusions and Relevance  This study suggests that cognitively healthy individuals with preclinical AD have retinal microvascular abnormalities in addition to architectural alterations and that these changes occur at earlier stages of AD than has previously been demonstrated. Longitudinal studies in larger cohorts are needed to determine whether this finding has value in identifying preclinical AD.