Diabetic Retinopathy May Signal Cerebral Disease, Cognitive Impairment

Diabetic Retinopathy. Pan Photocoagulation Scars. (Photo By BSIP/UIG Via Getty Images)
The findings suggest the retina may be a possible biomarker for cognitive decline.

Diabetic retinopathy (DR) is linked with an increased risk of structural abnormalities in the brain and cognitive impairment, even after adjusting for common comorbidities related to diabetes, according to investigators who analyzed nearly 30 studies to reach the conclusion The American Journal of Ophthalmology report recommends that ophthalmologists redouble their efforts to educate patients with diabetes about the threat to their retinal health and increased risk of cognitive decline, especially patients age 65 years and older.

Because the retina is brain-derived, it is believed that it may provide an easily accessible, noninvasive method of researching the pathology of the brain. Investigators posit that evaluating retinal parameters may help identify the biomarkers that increase the risk of cognitive impairment in patients with type 2 diabetes.

To investigate the association of DR with either cerebral structural abnormalities or cognitive impairment in patients with diabetes, researchers reviewed and analyzed 27 studies (83,585 patients).

They found:

  • The combined odds ratio of 5 cross-sectional/cohort studies reported that the associations between DR and cerebral structural changes were 1.75 (95% CI 1.36–2.25).
  • The combined hazard ratio of 4 cohort studies that examined the association between DR and cognitive impairment events was 1.47 (95%CI: 1.22–1.78).
  • The combined odds ratio of 14 cross-sectional/cohort studies that examined the association between DR and different cognitive impairment events was 1.43 (95% CI 1.06–1.93).
  • The overall coefficient of 4 studies that examined the relationship between DR and specific cognitive performance was 0.09 (95% CI 0.00–0.18). 

These linkages were still significant after adjusting for blood glucose levels, hemoglobin A1c, and the presence of hypertension, according to researchers. In addition, DR and cognitive impairment showed “a significant positive correlation” in studies employing multiple linear-regression analyses.

“According to our results, DR may help to predict cerebral disease and cognitive impairment,” the investigators report. “The diagnosis and treatment scheme in diabetes should include eye screening to improve the therapeutic effect and prevent severe cognitive decline as much as possible. Since the morbidity of dementia is especially high in older diabetic patients, a great effort to look after old patients with dementia could be saved if we can execute early detection for dementia by retinal examination and early intervention by neurologists.”

This study has several limitations, according to investigators. First, a limited number of studies reported the relationship between advanced DR and cognitive impairment. In addition, they noted publication bias in the meta-analysis of DR and cerebral structural changes and DR and cognitive impairment. Lastly, studies adjusted for diabetes duration, glycemia, and hypertension accounted for 70% of the research analyzed.


Chai YH, Zhang YP, Qiao YS, et al. Association between diabetic retinopathy, brain structural abnormalities and cognitive impairment for accumulated evidence in observational studies. Am J Ophthalmol. Published online January 17, 2022. doi:10.1016/j.ajo.2022.01.011.