Researchers at Duke Eye Center have demonstrated how a noninvasive imaging technique can rapidly detect changes to the retina that can indicate Alzheimer’s disease (AD). The technique, known as optical coherence tomography angiography (OCTA), detects changes to or deterioration of the tiny blood vessels at the back of the eye, and is being used by researchers to study the connection between the retina and Alzheimer’s disease.
Headed by Sharon Fekrat, MD, professor of ophthalmology at Duke, the new OCTA study, which the team claims is the largest of its kind so far, found changes in the different layers of retinal blood vessels in patients with Alzheimer’s disease when compared with healthy people and with individuals with mild cognitive impairment (MCI). “Early diagnosis of Alzheimer’s disease is a huge unmet need,” Fekrat said. “It’s not possible for current techniques like a brain scan or lumbar puncture (spinal tap) to screen the number of patients with this disease. It is possible that these changes in blood vessel density in the retina may mirror what’s going on in the tiny blood vessels in the brain.”
The researchers reported their findings today in Ophthalmology Retina, in a paper titled, “Retinal Microvascular and Neurodegenerative Changes in Alzheimer’s Disease and Mild Cognitive Impairment Compared with Control Participants.”
Alzheimer’s disease (AD) affects an estimated 5.5 million people in the United States alone, and is the most common subtype of dementia, the reporters noted. Symptoms of the disease include increasing memory deficits. MCI is considered to be a transitional stage between normal aging and dementia, and “an estimated 32% of MCI patients will progress to AD within 5 years’ follow-up,” the authors continued.
Current diagnostic methods for AD and MCI include those that aren’t feasible for screening millions of people. Brain scans are costly and spinal taps are invasive and carry some risks. Alzheimer’s disease is also commonly advanced before memory tests of behavioral changes can diagnose the condition. “Faster, more accessible, less invasive diagnostic techniques are a large unmet need for efficient screening of those at risk,” the team commented. Early diagnosis will help researchers investigate the effects of existing and development drugs, when administered earlier in the course of disease.
The retina is effectively an extension of the brain, and researchers reason that deterioration in the retina may mirror deterioration in blood vessels in the brains of Alzheimer’s disease patients, and so provide a more accessible option for diagnosis.
“We know that there are changes that occur in the brain in the small blood vessels in people with Alzheimer’s disease, and because the retina is an extension of the brain, we wanted to investigate whether these changes could be detected in the retina using a new technology that is less invasive and easy to obtain,” said Duke ophthalmologist and retinal surgeon Dilraj S. Grewal, MD, who is lead author on the study.
For their studies, the team harnessed OCTA to scan 70 eyes from 39 individuals with Alzheimer’s disease, 72 eyes from 37 participants with MCI, and 254 eyes from 133 healthy control participants. OCTA can image changes in tiny capillaries that aren’t visible on MRI or cerebral angiogram scans, which can only show changes in larger blood vessels. Importantly, the study adjusted for age and gender and their enrolment criteria excluded potential confounding factors such as diabetes, uncontrolled high blood pressure, glaucoma, age-related macular degeneration, and other eye diseases.
The OCTA scan results showed that individuals with Alzheimer’s disease exhibited loss of small retinal blood vessels—reduced superficial capillary plexus vessel density (VD) and perfusion density (PD)—when compared with healthy controls and with the MCI group. The macular ganglion cell-inner plexiform (GC-IPL) layer of the retina was also much thinner in Alzheimer’s disease participants than in the control group.
“We’re measuring blood vessels that can’t be seen during a regular eye exam and we’re doing that with relatively new noninvasive technology that takes high-resolution images of very small blood vessels within the retina in just a few minutes,” Fekrat noted. “It’s possible that these changes in blood vessel density in the retina could mirror what’s going on in the tiny blood vessels in the brain, perhaps before we are able to detect any changes in cognition.”
The authors suggested that the differences in blood vessel density indicate that “VD and PD may be imaging biomarkers useful in screening for AD in symptomatic individuals and may be able to distinguish between MCI and AD.” Their data also support those of a previous, smaller OCTA study that reported decreased SCP vascular density in the eyes of Alzheimer’s disease patients, and in addition support previous studies evaluating retinal vasculature using fundus photographs.
“Changes in the retinal microvasculature may mirror small-vessel cerebrovascular changes in AD,” the scientists concluded. “These parameters may serve as surrogate noninvasive biomarkers for the diagnosis of AD. Future studies are needed to determine whether such tests will be able to detect progression of MCI to AD.”
“Our work is not done,” Fekrat stated. “If we can detect these blood vessel changes in the retina before any changes in cognition, that would be a game changer … Ultimately, the goal would be to use this technology to detect Alzheimer’s early, before symptoms of memory loss are evident, and be able to monitor these changes over time in participants of clinical trials studying new Alzheimer’s treatments.”