ArticleThe Journal of international medical research2025
Causal associations between cognitive impairments and retinal diseases: A two-sample Mendelian randomization study.
Article in The Journal of international medical research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
ObjectiveThis study employed a bidirectional two-sample Mendelian randomization approach to investigate the causal links between Alzheimer's disease, Lewy body dementia, vascular dementia, and various retinal diseases.MethodsSummary data from large-scale genome-wide association studies of European ancestry were used to select genetic variants as instrumental variables. Causal estimates were derived using the inverse variance-weighted method, complemented by Mendelian randomization-Egger, weighted median, and weighted mode analyses to ensure robustness.ResultsGenetically predicted Alzheimer's disease was associated with a reduced risk of disorders of the choroid and retina (odds ratio = 0.93, 95% confidence interval: 0.88-0.98), retinal detachments and breaks (odds ratio = 0.90, 95% confidence interval: 0.84-0.97), and retinal detachment with retinal break (odds ratio = 0.84, 95% confidence interval: 0.74-0.95). Lewy body dementia was negatively associated with age-related macular degeneration (odds ratio = 0.88, 95% confidence interval: 0.79-0.98), disorders of the choroid and retina (odds ratio = 0.96, 95% confidence interval: 0.93-0.99), and degeneration of the macula (odds ratio = 0.93, 95% confidence interval: 0.88-0.98). Vascular dementia showed negative associations with age-related macular degeneration (odds ratio = 0.93, 95% confidence interval: 0.87-0.99) and degeneration of the macula (odds ratio = 0.96, 95% confidence interval: 0.93-0.99). Conversely, reverse Mendelian randomization indicated that genetic liability to macular degeneration and choroidal/retinal disorders was causally associated with cognitive performance and a reduced risk of Alzheimer's disease.ConclusionsFindings support inverse causal relationships in which specific dementias may reduce retinal disease risk and vice versa, suggesting complex shared biological mechanisms.
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