MRI Scans Link Eye Microvascular Health to Early Signs of Cognitive Decline

Is the eye a window to the brain?

Researchers at Rutgers University think so. A study led by doctoral candidate Gina Roslan and Joshua W. Miller, professor and chair, Department of Nutritional Sciences within the School of Environmental Sciences and Biological Sciences, is exploring whether microvascular abnormalities in the white of the eye can signal early neurodegenerative changes associated with age-related cognitive decline and Alzheimer’s disease.

The cross-campus project is in collaboration with and funded through a pilot grant from the Center for Advanced Human Brain Imaging Research in Rutgers Brain Health Institute.

The researchers use a noninvasive tool called computer-assisted intravital microscopy—first developed at the University of California, Davis—to record in real time tiny blood vessels in the white of the eye. This technology allows researchers to observe abnormalities in these microvessels as well as measure their sizes and blood flow speed.

Previous research with computer-assisted intravital microscopy has shown that unusual blood vessels in the eye are common in people with conditions such as diabetes, hypertension, and sickle cell disease. Roslan and Miller are investigating whether such pathology is associated with pathological changes in the brain that lead to age-related cognitive impairment and risk of Alzheimer’s disease and other types of dementia.

In the study, the researchers are working with adults ages 60 and older with and without mild cognitive impairment, which is an early sign of age-related cognitive decline that can precede the development of Alzheimer’s disease and dementia.

Study participants undergo both computer-assisted intravital microscopy imaging of their eyes, cognitive function assessment, and MRI imaging of their brains at the Center for Advanced Human Brain Imaging Research in BHI.

“Our initial findings show that participants with cognitive impairment have a greater number of microvessel abnormalities in the eye than those with normal cognitive function,” Roslan said.

The MRI scans showed that these participants have more changes in their brains, specifically a condition called white matter hyperintensity, which is indicative of neurodegeneration, and less of a key tissue called gray matter in the brain’s deeper parts.

The researchers also found that participants with cognitive impairment have higher levels of an amino acid called homocysteine in their blood. This amino acid tends to rise from low levels of certain B vitamins, such as folate, B12, and B6, and it’s also linked to a higher risk of heart attacks, strokes, and other blood vessel issues.

The study indicates that microvessel pathology in the eye and high homocysteine levels in the blood could be early indicators of neurodegenerative processes that lead to age-related cognitive decline, Alzheimer’s disease, and other forms of dementia.

“By identifying such early biomarkers, we envision that individuals at risk can be identified before clinical cognitive impairment occurs, and interventions, such as dietary changes, supplements, pharmaceuticals, weight management, control of diabetes and other lifestyle changes, may be most successful in slowing or preventing progression,” Miller said.

Computer-assisted intravital microscopy is currently limited to research settings. As more research demonstrates its clinical utility, the long-term goal is to integrate this technology into routine clinical practice.

While no identical eye vessel screenings for cognitive decline are widely available today, other eye imaging tools are in use for related health concerns. Optical Coherence Tomography Angiography (OCTA) is used to visualize the retinal microvasculature. It is available at some ophthalmology practices for conditions such as diabetic retinopathy, but its use for detecting cognitive decline is still under investigation, Roslan added.

“The interdisciplinary study highlights Rutgers’ cross-campus collaboration, bringing together expertise in nutritional sciences and advanced brain imaging to address a critical public health challenge,” Miller said.

Co-investigators on this project include William Hu, chief of Cognitive Neurology and Alzheimer’s Disease Clinic at Robert Wood Johnson Medical School and RWJBarnabas Health Medical Group as well as director of the Rutgers Center for Healthy Aging Research; and David H. Zald, director of the Center for Advanced Human Brain Imaging Research and Henry Rutgers Professor of Psychiatry at Robert Wood Johnson Medical School. 

“This research fills a gap in our understanding of age-related cognitive decline by linking eye health to brain function,” Hu commented. “By identifying early, non-invasive biomarkers, we can empower older adults to take proactive steps to protect their cognitive health.”

Zald said the center’s advanced brain-imaging resources enable this kind of interdisciplinary collaboration. “By providing scanner access, technical guidance for integrating behavioral tasks into imaging protocols, analysis support, and pilot funding, our team is able to support researchers from different fields as they collaborate on important work like this,” he said.