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Diabetic retinopathy (DR) had a significant association with multiple types of neurodegenerative disorders, particularly cognitive impairment, a large meta-analysis showed.

DR more than doubled the odds for subsequent development of systemic neurodegeneration and also increased the odds of a current neurodegenerative disorder. Severity of retinopathy did not influence the likelihood of systemic neurodegeneration, reported Frederik N. Pedersen, MD, of Odense University Hospital in Denmark, and colleagues.

Though far from definitive, the results make a case for additional studies to examine the associations, they stated in .

"It is worth noting that studies [included in the meta-analysis] were equivocal in their findings and most of the available studies evaluated cognitive function and impairment," the authors acknowledged. "These circumstances call for large, better-controlled observational studies. Further, it is not known whether improvement of DR influences cognitive function, and interventional clinical studies are warranted to evaluate the practical clinical importance of DR in relation to cognitive function."

"Finally, diagnosis-specific studies were sparse, which further challenges the clinical importance of these findings," they stated. "Nevertheless, statistically significant ORs [odds ratios] at 1.57 and 2.36 on cross-sectional and longitudinal studies, respectively, are uniform in suggesting effect sizes that deserve further attention."

The findings add to those of previous studies suggesting that patients with diabetic eye disease have an increased risk for several systemic diseases, including neurodegenerative disorders, said Sunir Garg, MD, of Wills Eye Hospital and Thomas Jefferson University in Philadelphia.

"We know that diabetes affects the small blood vessels throughout the body," Garg, a clinical spokesperson for the American Academy of Ophthalmology, told 番茄社区app via email. "This includes the retina, the kidneys, the heart, as well as the brain. Additionally, diabetes causes damage due to inflammation, scar tissue formation, and death of nerve cells. Some of these changes are also seen in neurodegenerative diseases."

The data analyzed by Pedersen and colleagues seem to suggest that diabetic eye disease increases the risk of neurodegenerative disorders, irrespective of the severity of diabetic retinopathy, he added. Nonetheless, "patients should not assume that simply because they have diabetic eye disease that they are going to develop neurodegenerative disease as well. It does highlight the importance of helping our patients with diabetes to control their sugar and blood pressure to reduce the likelihood of developing any complications from diabetes."

Patients with diabetes should have an annual eye exam by an ophthalmologist as part of their routine care, Garg added.

The association between DR and neurodegenerative disorders has attracted interest, in part, because the retina and optic nerve are brain-derived tissues and have similar pathogenic pathways, the authors noted. Previous research showed an increased incidence of and in patients with diabetes. Brain MRI of patients with DR showed an increased prevalence of and as compared with people who did not have diabetic eye disease.

The collective evidence suggested "a future scenario, when retinal neurodegeneration could be an important factor in identifying individuals at risk for systemic neurodegenerative diseases," the authors stated. To investigate the issue, Pedersen and colleagues performed a systematic literature review to identify studies of Alzheimer's disease, Parkinson's disease, and cognitive impairment in association with diabetic eye disease (retinopathy, angiopathy, or maculopathy).

They identified 27 studies for a qualitative review, 14 of which provided data for the meta-analysis. Of the 27 studies, 13 were cross-sectional, 11 were cohorts, and three were case-control studies. Three studies involved Alzheimer's disease, one involved Parkinson's, and the rest involved the association between diabetic eye disease and cognitive impairment. Collectively, the studies included 1,398,041 patients with diabetes, and type 2 diabetes accounted for 1,379,544 of the total.

Analysis of the cross-sectional studies showed that patients with DR had an OR of 1.57 for a current neurodegenerative disorder (95% CI 1.02-2.43, P=0.043), and analysis of longitudinal investigations yielded an OR of 2.36 for incident neurodegeneration (95% CI 1.50-3.71, P=0.00021). The odds of systemic neurodegeneration was not affected by severity of DR (OR 0.98, 95% CI 0.45-2.15).

With regard to studies of different types of neurodegeneration, eight of 13 cross-sectional investigations showed one or more associations between DR and cognitive impairment, as did all three case-control studies included in the analysis. Seven cohort studies yielded one or more findings that implicated DR as a risk for future development of cognitive impairment. Two of three cohort studies showed significant associations between DR and future development of Alzheimer's disease or dementia. The one study that analyzed DR and Parkinson's disease showed a significant association with future risk of the neurodegenerative disorders among patients with DR.

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