Can Retinal Imaging Unlock Clues to Alzheimer’s?

Thursday, September 4 2025 | 17 h 36 min | News

Alzheimer’s disease and related dementias (ADRD) remain some of the most pressing challenges in healthcare today. Despite advances in neuroimaging and blood-based biomarkers, clinicians still struggle to identify the disease in its earliest stages, when interventions may be most effective. A growing body of research is now turning to the retina as a potential window into brain health.

A recent (August 2025) study published in Alzheimer’s & Dementia provides fresh evidence supporting this approach. Researchers at The Jackson Laboratory in Maine investigated whether retinal vascular changes in mice carrying a common Alzheimer’s-linked genetic variant mirror those occurring in the brain. Their findings suggest that subtle shifts in retinal blood vessels could serve as early indicators of cerebrovascular dysfunction tied to dementia risk.

For eye care professionals who routinely conduct retinal exams and imaging, this research offers a glimpse into a future where the clinic may play a central role in early dementia detection.

Why the Retina Matters

The retina shares structural and functional similarities with the brain. Unlike the brain, however, it is easily accessible through non-invasive imaging. This makes it an attractive candidate for detecting early biomarkers of neurological disease.

Previous work has largely focused on amyloid plaques in the retina, but there is growing interest in vascular changes. Cerebrovascular dysfunction, including small vessel disease, impaired perfusion, and blood–brain barrier disruption is believed to occur years before noticeable cognitive decline. Because retinal and cerebral blood vessels are so closely linked, changes in one may reflect changes in the other (Alzheimer’s & Dementia, 2025).

The Glaucoma – Dementia Gene Link

The study centered on a well-known genetic variant in the methylenetetrahydrofolate reductase (MTHFR) gene, known as C677T. This variant is carried by an estimated 20–40% of the global population. It has been linked not only to vascular dementia and Alzheimer’s disease but also to primary open-angle glaucoma and retinal vascular occlusion (Alzheimer’s & Dementia, 2025).

Using a mouse model engineered with this genetic variant, the researchers tracked changes in retinal vasculature over time and compared them with brain changes. Their methods included fundus photography, fluorescein angiography, and proteomic analysis.

What They Found

The researchers observed a range of vascular changes in the retinas of mice carrying the MTHFR variant. These changes paralleled what was happening in the brain, including:

• Reduced vascular density: Particularly in 12-month-old female mice, there was a noticeable drop in retinal vessel density and fewer branching vessels, echoing previous observations of reduced brain vessel density.
• Vessel abnormalities: Mice showed an increased number of arteriovenous crossings, vessel tortuosity (twisting), narrowed arterioles, and enlarged venules. These patterns resemble vascular phenotypes seen in human ocular and systemic disease.
• Protein overlap: The study identified differentially expressed proteins in both brain and retina that are relevant to Alzheimer’s pathology, including pathways related to metabolism, mitochondrial function, and cell survival.

Interestingly, retinal thickness and ganglion cell function did not show significant changes, suggesting the variant alone was not producing glaucoma-like damage. This strengthens the case that vascular changes, not neuronal loss, may be the earliest signals (Alzheimer’s & Dementia, 2025; Medical News Today).

Why It Matters for Eye Care Professionals

For optometrists these findings reinforce the value of routine retinal imaging not only for ocular disease management but potentially as a frontline screening tool for neurodegenerative risk.

Retinal vascular features such as vessel caliber, branching patterns, and tortuosity are already visible through commonly used technologies including fundus photography, OCT angiography, and fluorescein angiography. If validated in human populations, these same tools could provide non-invasive biomarkers for Alzheimer’s risk long before cognitive symptoms arise.

As Maya Koronyo-Hamaoui, PhD, a neuroscientist at Cedars-Sinai not involved in the study, commented to Medical News Today:

“This study strengthens the ‘eye–brain’ axis for neurodegeneration. The data argue that the retina can report on disease-linked vascular biology in the brain, and that quantitative retinal imaging might serve as a minimally invasive readout of risk.”

Limitations and Next Steps

While promising, the study has important caveats:

• Mouse model data: Results are based on animal studies. Human validation is essential before clinical translation.
• Timing of changes: Reduced retinal vessel density was only observed at 12 months in mice, whereas brain changes appeared earlier. This suggests some retinal biomarkers may lag behind cerebral ones.
• Specificity: Vascular changes in the retina are not unique to dementia—they are also linked to hypertension, diabetes, stroke, and other conditions. Distinguishing dementia-specific patterns will be critical.

Daniel Romaus-Sanjurjo, PhD, of the Health Research Institute of Santiago de Compostela, highlighted these challenges in Medical News Today:

“The vascular changes observed in this study can be related to other diseases (e.g., stroke), so this study should be taken carefully. More data is needed to clarify whether ocular changes occur before or after brain changes, and which ones are dementia-specific.”

Looking Ahead

The promise of retinal imaging as a biomarker for Alzheimer’s and related dementias lies in its accessibility. Eye exams are routine, safe, and already part of the standard of care for millions of patients annually. If future research confirms that subtle vascular changes in the retina align with early dementia pathology, eye care professionals could become key partners in the early detection of neurodegenerative disease.

• Incorporating vascular biomarker screening into routine retinal imaging protocols.
• Collaborating with neurologists and primary care providers to flag patients at risk.
• Expanding the role of eye exams in systemic disease detection, reinforcing optometry and ophthalmology as gateways to overall health monitoring.

This study adds to a growing body of evidence that the retina may provide a clear window into the brain. By revealing how a common genetic risk factor for dementia affects both cerebral and retinal vasculature, the research underscores the potential of routine eye exams to aid in earlier detection of Alzheimer’s and related dementias.

For eye care professionals, the findings highlight a possible expansion of the profession’s role in systemic health. While more human data is needed before retinal imaging can be adopted as a clinical biomarker, the path forward suggests that what eye care providers already do best—looking closely at the retina—could one day help unlock earlier, more effective interventions for patients at risk of dementia.