Association of Preclinical Alzheimer Disease With Optical Coherence Tomographic Angiography Findings

Abstract

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.

Conflict of interest statement

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Figures

Figure 1.. Foveal Avascular Zone (FAZ) Measurements

Measurements were obtained using optical coherence tomography (OCT) angiography (Avanti OptoVue; OptoVue). Top images depict the angiogram with nonflow areas of 0.212 mm2 (A) and 0.311 mm2 (B); bottom images, OCT scans.

Figure 2.. Foveal Thickness and Foveal Avascular Zone (FAZ) Measurements

Data are shown as box and whisker plots, where whiskers represent 1.5 times the interquartile range. A, Positron emission tomography (PET) imaging results are shown for fluorine 18–labeled florbetapir compound testing. Open circles indicate outliers. B, Cerebrospinal fluid (CSF) analysis results are shown for β-amyloid 42 and τ protein biomarkers. C and D, Participants with negative findings for all biomarkers (PET and/or CSF) were compared with those with positive findings for at least 1 test.

Figure 3.. Receiver Operating Characteristics Curve for Foveal Avascular Zone (FAZ)

The receiver operating characteristics curve shows sensitivities (true-positive rate) and specificities (false-positive rate) of the FAZ comparison between all participants with biomarker-positive and biomarker-negative findings. Area under the curve is 0.8007 (95% CI, 0.6647-0.9367). Lower CI limits were also calculated for the data point closest to the nondiscriminatory (diagonal) line, assuming a normal distribution and a binomial distribution of the data.