Damage to the blood-retinal barrier is present in both diabetic retinopathy and several forms of dementia, likely leading to the association found in this study.

Damage to the blood-retinal barrier is present in both diabetic retinopathy and several forms of dementia, likely leading to the association found in this study. Photo: University College London Institute of Ophthalmology. Click image to enlarge.

Editor’s Note: As part of our “Year in Review” retrospective, we’ve selected the top 30 news stories of the year and are re-sharing them as we close out 2022. Follow along as we count down to number 1!

This story was originally published on December 16, 2022. 

No. 4 biggest news story of 2022:

Upon investigating whether associations between diabetic retinopathy (DR) and dementia and Alzheimer’s disease (AD) remain significant after controlling for several measures of diabetes severity, researchers recently found that among people with type 2 diabetes, DR and resulting glycemic and renal complications appear to be an important biomarker of dementia risk.

This retrospective cohort study included 536 adults ≥65 years who were dementia-free at enrollment and were followed biennially until incident dementia developed. Participants either had or developed type 2 diabetes. Estimates of microalbuminuria, long-term glycemia and renal function from longitudinal laboratory records were used as indicators of diabetes severity.

The team found significant associations between DR of greater than five years duration and both dementia and AD. They noted these associations persisted even after adjusting for estimates of microalbuminuria, long-term glycemia or renal function. “The strong association,” the researchers wrote in their paper on the work,  “despite controlling for several markers of diabetes severity suggests that the factors accounting for this association may be specific to the retina and the brain.” Even though the pathophysiologic mechanisms differ considerably between AD and non-AD dementia, a history of DR more more than five years “appears to be an important biomarker associated with increased risks of both AD and all-cause dementia development,” they explained in their paper.

Damage to the neurovascular unit, including damage to the inner blood-retinal barrier (BRB) and the blood-brain barrier (BBB), may be a key mechanism underlying both diabetic retinopathy and dementia, the researchers suggest. “The breakdown of the BRB is a known feature of DR, and BRB pathology has also been found in AD. In addition, BBB breakdown has been implicated as an early event in the AD pathology cascade.” Citing a prior study, the authors explained that “Type 2 diabetes patients with retinal neuro- and vaso-degeneration were at higher risk for rapid cognitive decline and AD, while those without these retinal pathologies exhibited lower rates of cognitive decline.

“These findings suggest that the course of DR in people with diabetes could provide useful information on dementia risk,” the study authors concluded. “Further, a deeper understanding of the causal pathways underlying the association between DR >five years and dementia could offer useful insights on dementia.”

Lee CS, Krakauer C, Su YR, et al. Diabetic retinopathy and dementia association, beyond diabetes severity. Am J Ophthalmol. December 10, 2022. [Epub ahead of print].