LOS ANGELES -- Preclinical Alzheimer's disease may be identifiable through optical coherence tomography (OCT) and OCT angiography, researchers from Washington University in St. Louis .
"There's evidence that there are retinal changes in Alzheimer's disease," said lead investigator Gregory Van Stavern, MD, at the 's annual meeting.
"There's a body of literature looking at OCT metrics in patients with established Alzheimer's disease and cognitive dysfunction that shows some evidence of vascular and microvascular dysfunction in the retina."
Whether similar retinal changes occur in preclinical Alzheimer's patients was unknown. To find out, researchers recruited people from the Washington University Alzheimer's Disease Research Center who were cognitively normal and had either positron emission tomography (PET) or cerebrospinal fluid (CSF) analysis to assess Alzheimer's disease in the past year. They excluded people with trauma, underlying ophthalmic disease, elevated intraocular pressure, high refractive error, diabetes, and hypertension.
Each participant underwent a complete neuro-ophthalmic examination and OCT angiography, a noninvasive imaging technique that allows retinal and microvascular anatomy to be analyzed. Through OCT angiography, the researchers assessed the retinal nerve fiber layer thickness, ganglion cell layer thickness, foveal thickness, vascular density, macular volume, and data about the foveal avascular zone of each participant.
Of the 30 patients in the study, 16 were biomarker-negative for Alzheimer's disease; 14 were biomarker-positive and were classified as having preclinical Alzheimer's.
In the biomarker-negative group, the average age was about 74; 63% were female and 100% were Caucasian. In the biomarker-positive group, the average age was about 75 years; 42% were female and 92% were Caucasian. Intraocular pressure was about 14 in each group.
The researchers found that people who were biomarker-positive had inner foveal thinning (75.4 versus 66 μm), "which is congruent with the body of literature looking at OCT in established Alzheimer's disease," according to Van Stavern.
They also found that biomarker-positive individuals had an enlarged foveal avascular zone (0.30 mm2 versus 0.40 mm2).
"The mechanism for this -- assuming this is a valid result -- is still not entirely clear," Van Stavern noted, but could be due to capillary deposition of collagen and amyloid, resulting in cellular apoptosis and vessel drop-out.
"What this means -- again, assuming we can replicate this and show it's a valid result -- is that it's possible we could identify Alzheimer's disease in the preclinical stage using biomarkers that are less invasive and less cumbersome than PET and CSF," he said.
"This is really where the field is headed -- to identify patients in the preclinical stage before there's too much neuronal loss, and to potentially intervene," he added. "There already are ongoing clinical trials for preclinical Alzheimer's disease."
The research is limited by its small sample size and the fact it was conducted in a single study center with a limited number of minority participants. For some people in the study group, only one Alzheimer's disease biomarker was available.
The researchers continue to recruit participants and will include people with early Alzheimer's disease in future studies.
Disclosures
This study was supported by Optovue, Inc., developers of OCT angiography. The researchers reported no conflicts.
Primary Source
American Academy of Neurology
Van Stavern G, et al "Optical coherence tomography angiography in pre-clinical Alzheimer's disease" AAN 2018.