DR Severity May Signal Stepwise Risk in Dementia

Investigators reported that increasing diabetic retinopathy severity was linked to higher risk of all-cause dementia and vascular dementia in patients aged 65 and older. In contrast, Alzheimer’s risk did not vary by retinopathy stage, suggesting that diabetes itself, rather than retinal disease severity, may drive AD development and reinforcing the potential role of routine eye examinations in identifying patients who may benefit from early cognitive screening. Photo: Jay Haynie, OD. Click image to enlarge. The public health concerns around dementia, Alzheimer’s disease (AD) and vascular dementia (VD) have contributed to ongoing research into risk identification. Several studies have found a link between diabetes mellitus and these diseases, suggesting shared pathophysiological mechanisms such as impaired insulin signaling, inflammation and oxidative stress. As diabetic retinopathy (DR) may be a potential marker or proxy for other systemic conditions, a group of researchers in the US decided to explore whether DR severity impacts dementia risk, the results of which were recently published in American Journal of Ophthalmology. Using the TriNetX database of health records from 153 healthcare organizations worldwide, the researchers identified four cohorts: 14,034 individuals with proliferative diabetic retinopathy (PDR), 29,188 with nonproliferative diabetic retinopathy (NPDR), 208,640 with type 2 diabetes (DM2) without DR and 447,054 without diabetes, all of whom were aged 65 or older. Cohorts underwent 1:1 propensity score matching to account for baseline differences.  According to the results, all three diabetic groups were each associated with significantly increased risk of all-cause dementia, AD and VD compared to healthy subjects, as follows: All-cause dementiaAlzheimer’sVascular dementiaPDR15.9% vs. 10.2%2.7% vs. 2.2%3.6% vs. 1.7%NPDR16.6% vs. 11.3%3.4% vs. 2.5%3.7% vs. 1.8%Diabetes without DR14.4% vs. 10.8%3.2% vs. 2.6%2.5% vs. 1.7% Those with PDR and NPDR had higher risk for all-cause dementia and VD, but not AD. When stratified by DR severity, PDR was associated with a higher risk of all-cause dementia and VD, but not AD, compared to NPDR. No association was seen with AD based on DR severity.“Our study demonstrated that the presence and severity of DR in individuals with DM2 was associated with a stepwise increase in risk of all-cause dementia and VD,” the authors wrote in their paper. They noted that these risks rose progressively with advancing DR severity, while the risk of AD did not, “suggesting that diabetes itself, rather than the severity of retinopathy, drives AD risk.”This study aligns with others that have demonstrated an association between all-cause dementia and vascular dementia, but it conflicted with those that link DR to Alzheimer’s, the authors wrote. This may be due to methodological differences, such as excluding those with diabetic macular edema. There also may have been survivorship bias due to the significant age gap between the mean age of this study’s PDR cohort at diagnosis of DR (69.1 years) and the typical age of onset of AD (80+ years).The observation that all-cause dementia and VD risk increases incrementally with DR severity is the novel contribution of this study, according to the authors. This suggests that DR serves as a biomarker for vulnerability to dementia, particularly VD. “Patients with DR often experience years of microvascular damage before any cognitive symptoms appear, making them a target population for dementia screening,” they wrote in AJO. “Routine ophthalmologic examinations, already standard of care in diabetes management, represent an accessible platform for dementia risk assessment and early intervention.”The retrospective nature of this study, which relied on variable ICD coding practices across institutions, is a potential limitation noted by the researchers. They were also unable to accurately capture education and socioeconomic status factors. Additionally, the average follow-up time (6.7 years) may have been insufficient for younger participants who may not have reached the age of typical dementia onset. Ultimately, these findings underscore the role of systemic microvascular injury in cognitive decline. The authors emphasized the role of eye care clinicians to alert or refer patients with DR to their primary care providers for additional dementia screening.Click here for the journal source. Khangura, MS. et al. The association between diabetic retinopathy severity and dementia risk: A TriNetX longitudinal cohort study. AJO. February 13, 2026. [Epub ahead of print.] This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.