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The cross-sectional and longitudinal relationship of diabetic retinopathy to cognitive impairment: a systematic review and meta-analysis



To establish a potential relationship between diabetic retinopathy (DR) and different stages of cognitive impairment


Literature searches were conducted on PubMed and EMBASE, with keywords “diabetic retinopathy” and “cognitive impairment”. Inclusion criteria were original human studies, and English language. Quality of studies was assessed by the Newcastle-Ottawa Quality Assessment (NOSGEN). The register number of this study on the International Prospective Register of Systematic Reviews (PROSPERO) is CRD42021236747. The main outcome measures were odds ratios (OR) and risk ratios (RR) for cross-sectional and longitudinal studies, respectively. Meta-regression was performed to evaluate the effects of potential moderator variables, including, age, onset age of diabetes mellitus (DM), duration of DM, and HbA1c.


Twenty-five studies (17 cross-sectional and 8 longitudinal studies) with a total of 1,963,914 subjects, were included. Among the cross-sectional studies, the pooled ORs of any cognitive impairment, early stage of cognitive impairment and dementia in subjects with DR (95% confidence interval) were 1.48 (1.08–2.02), 1.59 (1.01–2.51), and 1.13 (0.86–1.50), respectively. Among the longitudinal studies, the pooled RRs of any cognitive impairment, early stage of cognitive impairment, and dementia in subjects with DR (95% confidence interval) were 1.35 (1.12–1.65), 1.50 (1.06–2.12), and 1.31 (1.03–1.66), respectively. Meta-regression showed age, onset age of DM, duration of DM, and glycated hemoglobin (HbA1c) were not statistically associated with the outcomes.


The presence of DR in DM patients indicates both higher odds of prevalent cognitive impairment and escalated risks of developing cognitive impairment in the future.





PubMde 和 EMBASE数据库中使用“糖尿病视网膜病变”和“认知障碍”两个关键词进行文献检索。纳入标准为临床研究和英文文献, 我们通过Newcastle-Ottawa质量评估(NOSGEN)方法评估研究质量。本研究在国际前瞻性系统性综述登记研究(PROSPERO)中的登记研究编号为CRD42021236747。比值比 (OR) 和风险比 (RR) 分别是横断面研究和纵向研究的主要结局指标。荟萃-回归分析用以评估潜在调节变量带来的影响, 包括年龄、糖尿病(DM)发病年龄、DM病程和HbA1c。


共纳入25项研究 (17项横断面研究和8项纵向研究), 一共1, 963, 914例受试对象。在横断面研究中, DR受试者中任何认知障碍、早期认知障碍及痴呆的合并OR (95%置信区间) 分别为1.48(1.08–2.02)、1.59(1.01–2.51)和1.13(0.86–1.50)。在纵向研究中, DR受试者中任何认知障碍、早期认知障碍及痴呆的合并RR (95%置信区间) 分别为 1.35 (1.12–1.65), 1.50 (1.06–2.12) and 1.31 (1.03–1.66)。荟萃-回归分析显示, 年龄, DM发病年龄, DM病程和糖化血红蛋白 (HbA1c) 与认知障碍结局无统计学相关性。


并发DR的DM患者发生认知障碍的几率高, 且将来发生认知障碍的风险也高。

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Fig. 1
Fig. 2: Meta-analysis for cross-sectional association between DR and any cognitive impairment.
Fig. 3: Meta-analysis for longitudinal association of DR and any cognitive impairment.
Fig. 4: Meta-analysis for cross-sectional association of DR and early stage of cognitive impairment.
Fig. 5: Meta-analysis for longitudinal association of DR and early stage of cognitive impairment.
Fig. 6: Meta-analysis for cross-sectional association of DR and dementia.
Fig. 7: Meta-analysis for longitudinal association of DR and dementia.
Fig. 8: Meta-analysis for cross-sectional association of PDR and any cognitive impairment.


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Health and Medical Research Fund, Hong Kong (Grant Number: 04153506). The funding organization had no role in the design or conduct of this research.

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RNFC was responsible for registering the protocol, conducting literature search, screening potentially eligible studies, extracting and analysing data, interpreting results, and writing the paper. ZT and VTTC contributed to data analysis, results interpretation, and writing the paper. RNCC, ETWC, and NCYN were responsible for designing the review protocol, writing the protocol, screening potentially eligible studies, and extracting and analysing data. CYC was responsible for designing the study, provided instructions on the paper, and supervised the entire process.

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Correspondence to Carol Y. Cheung.

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Chan, R.N.F., Tang, Z., Chan, V.T.T. et al. The cross-sectional and longitudinal relationship of diabetic retinopathy to cognitive impairment: a systematic review and meta-analysis. Eye 37, 220–227 (2023).

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