Diabetic retinal disease studies link DME and retinopathy severity to higher dementia risk
Two studies of older adults with type 2 diabetes linked diabetic retinal disease with higher dementia risk. DME and more severe diabetic retinopathy were associated with higher all-cause and vascular dementia risk, but not consistently with Alzheimer’s disease.
Diabetic retinal disease was linked to higher dementia risk in two studies of older adults with type 2 diabetes. Individuals with diabetic macular edema (DME) appeared to have a meaningfully greater chance to also develop vascular dementia or dementia from any cause, while a greater severity of diabetic retinopathy was associated with a stepwise increase in the risks for vascular and all-cause dementia but not Alzheimer’s disease.
In a longitudinal study presented at the Association for Research and Vision in Ophthalmology Annual Meeting, investigators employed the TriNetX global database to gather cohort members. Participants were at least 65 years of age with at least 1 eye evaluation or imaging with optical coherence tomography, and the research team put together 3 groups using ICD codes: patients with type 2 diabetes mellitus, those with type 2 diabetes-related DME, and control individuals without diabetes.
An analysis of dementia onset during follow-up showed greatly increased hazard ratios compared with control participants only for DME vs control group for risk of all-cause dementia, HR, 1.26 (95% CI, 1.17 to 1.35; P <.0001), and for vascular dementia, HR, 1.32 (1.15 to 1.50; P <.0001). Results applying a minimum of 7 or more years follow-up revealed stronger associations: DME vs type 2 diabetes for all-cause dementia, HR, 1.19 (95% CI, 1.09 to 1.23; P =.0001); DME vs control group for all-cause dementia, HR, 1.39 (1.27 to 1.52; P <.0001); DME vs type 2 diabetes for vascular dementia, HR, 1.31 (1.10 to 1.56; P =.0025); and DME vs control group for vascular dementia, HR, 1.55 (1.30 to 1.84; P <.0001). Further, weak or nonsignificant relationships appeared between DME and Alzheimer disease.
In a retrospective cohort study published online in the American Journal of Ophthalmology, researchers analyzed data of 769,930 individuals aged 65 years or older who underwent an eye exam or optical coherence tomography between January 2010 and January 2020 to examine the risk for dementia linked to diabetic retinopathy. Participants were categorized into four groups: 14,034 with proliferative retinopathy, 29,188 with nonproliferative retinopathy, 208,640 with only type 2 diabetes, and 447,054 control individuals without the condition; the groups were matched subsequently to account for differences at baseline. The study excluded individuals younger than 65 years, those with macular edema, and those with a diagnosis of dementia made before their diagnosis of diabetes.
Patients with diabetes only, patients with nonproliferative retinopathy, and patients with proliferative retinopathy had higher risks for all-cause dementia, Alzheimer’s disease, and vascular dementia than control individuals. Compared with participants with only type 2 diabetes, those with nonproliferative retinopathy and those with proliferative retinopathy had higher risks for all-cause dementia and vascular dementia but not for Alzheimer’s disease. When stratified by severity of diabetic retinopathy, proliferative retinopathy was associated with higher risks for all-cause dementia and vascular dementia than nonproliferative retinopathy, but no significant association was found between severity and the risk for Alzheimer’s disease.
The mean duration of follow-up in the diabetic retinopathy study was approximately 6.73 years. The DME study noted that the link between retinal diseases and neurodegeneration points to a potential role in monitoring DME patients for cognitive decline, and the diabetic retinopathy study stated that ophthalmic examinations, already routine in diabetes management, provide a valuable opportunity for dementia risk assessment and education.
Limitations included the retrospective design in the DME analysis. In the diabetic retinopathy study, education and socioeconomic status were not well captured in the database, follow-up of approximately 6.7 years may have been insufficient for younger participants, and the database did not provide age at death, preventing assessment of survival bias and duration of dementia.