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Resting-state brain functional alterations in diabetic retinopathy relate to cognitive domains and 1,101 genesBrain scans reveal how diabetic retinopathy affects memory and learning

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Key Takeaway
Note that resting-state brain alterations in diabetic retinopathy are associated with cognitive domains and 1,101 genes.

This coordinate-based neuroimaging meta-analysis investigates resting-state brain functional measures in patients with diabetic retinopathy (DR). The study identifies specific regions of altered activity, including increased measures in the left cerebellum and corpus callosum, and decreased measures in the left calcarine fissure, left middle occipital gyrus, two clusters in the right postcentral gyrus, right anterior cingulate cortex, and right middle temporal gyrus.

Functional decoding analysis associated these regions with cognitive domains involving language, learning, and cognition. Furthermore, a spatial transcriptomic-neuroimaging analysis linked the regional neuroimaging phenotype to the normative expression patterns of 1,101 genes. Functional enrichment analysis indicated these genes were enriched in processes related to learning, memory, and cognition, as well as biological processes involving cell adhesion and metal ion regulation.

The study provides potential insights into the molecular and cellular context of cognitive-related brain alterations associated with DR. However, the results represent associations rather than direct causation between DR and specific cognitive outcomes. The findings may assist in understanding the underlying mechanisms of cognitive changes in this population.

How this fits prior evidence

This meta-analysis addresses a gap in understanding the neurological and molecular context of diabetic retinopathy. While previous coverage has identified metabolic mediators like O-GlcNAc and inflammatory drivers like CD4+ T cell imbalances in other diabetic complications, this study specifically links DR to cognitive-related brain alterations and 1,101 genes related to memory and learning.

Living with diabetes can lead to a condition called diabetic retinopathy, which affects the eyes. While we often focus on vision, new research suggests this condition may also be linked to changes in how the brain processes information. By looking at brain scans from patients with the condition, researchers identified specific areas where brain activity changed.

Some areas, like the left cerebellum, showed increased activity. Other areas, including parts of the brain involved in processing sensory information and memory, showed decreased activity. These specific locations are tied to important cognitive skills like learning and language. The study also linked these brain patterns to over 1,000 genes involved in memory and cell health.

It is important to remember that these findings show a link between the condition and brain activity, not a direct cause. Because the study used a mix of imaging and gene data, we cannot say for certain how these changes affect a person's daily life. However, these results offer a new way to look at the underlying biology of the disease.

What this means for you:
Brain scans show that diabetic retinopathy is linked to changes in areas of the brain that manage memory and learning.

Common questions

What did the brain scans show in patients with diabetic retinopathy?

The scans showed that brain activity increased in the left cerebellum and corpus callosum. However, activity decreased in several other areas, including the left calcarine fissure, right anterior cingulate cortex, and right middle temporal gyrus. These areas are linked to functions like language and learning.

Does this mean diabetic retinopathy causes memory loss?

The study shows an association between the condition and changes in brain activity, but it does not prove that the condition causes specific cognitive outcomes. These findings provide a look at the molecular and cellular context of the disease.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedSep 2026
View Original Abstract ↓
IntroductionPatients with diabetes may develop cognitive dysfunction, particularly at advanced stages of the disease, manifested by impairments in learning, memory, language, and judgment. Previous studies have reported abnormal brain functional alterations in patients with diabetic retinopathy (DR), which may be associated with cognitive impairment in diabetes; however, the molecular correlates of these brain alterations remain poorly understood.MethodsIn this study, we performed a coordinate-based neuroimaging meta-analysis to identify convergent resting-state brain functional alterations in patients with DR. By integrating the meta-analytic imaging phenotype with gene-expression data from the Allen Human Brain Atlas, we further conducted spatial transcriptomic -neuroimaging analyses to identify genes whose normative expression patterns were spatially associated with DR-related brain functional alterations.ResultsThe meta-analysis revealed relatively increased resting-state functional measures in the left cerebellum and corpus callosum, whereas relatively decreased measures were observed in the left calcarine fissure, left middle occipital gyrus, two clusters in the right postcentral gyrus, right anterior cingulate cortex, and right middle temporal gyrus. Functional decoding analyses indicated that these regions were associated with cognitive domains involving language, learning, and cognition. In addition, the regional neuroimaging phenotype was spatially associated with the normative expression patterns of 1,101 genes. Functional enrichment analyses indicated that these genes were enriched in processes related to learning, memory, and cognition, as well as biological processes involving metal ion regulation and cell adhesion. Cell- and tissue-specific enrichment analyses further suggested preferential expression patterns involving retinal and cortical neuronal populations.DiscussionCollectively, these findings demonstrate convergent resting-state brain functional alterations in patients with DR and reveal their spatial correspondence with normative gene-expression patterns, providing potential insights into the molecular and cellular context of cognitive-related brain alterations associated with DR.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD420261292056.
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