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This study aimed to evaluate the bidirectional association between the kidney dysfunction and the brain health, including structural and functional abnormalities.Systematic review and meta-analysis with network meta-analysis for outcomes with different estimated glomerular filtration rate (eGFR) ranges.PubMed, Embase database, Cochrane library and Web of Science (up to Dec. 2021).Longitudinal studies that provided evidence of the impact of kidney function estimated from eGFR and urine albumin-to-creatinine ratio (UACR) or chronic kidney disease (CKD) on structural and functional brain abnormalities, and those that provided evidence of the opposite relationship. Studies with study population mean age under 18 years old were excluded.Two independent reviewers screened the included studies, extracted the data, and assessed the risk of bias. We performed a random-effects meta-analysis and a network meta-analysis for outcomes with compatible data. We assessed the risk of bias using the Newcastle-Ottawa Quality Assessment Scale criteria (NOS). Subgroup and sensitivity analyses were conducted to explore heterogeneity in the meta-analyses. Inconsistency analyses using the node-splitting method were performed to confirm the results of network meta-analysis.A total of 53 studies with 3037,357 participants were included in the current systematic review. Among these, 16 provided evidence of structural brain abnormalities, and 38 provided evidence of cognitive impairment and dementia. Analysis of evidence of categorical kidney function showed a positive association between kidney dysfunction and cerebral small vessel disease (cSVD) (relative risk (RR) 1.77, 95% confidence interval (CI) 1.40-2.24, IIn this systematic review and meta-analysis, we found a positive association between CKD and functional brain disorders. However, the relationship between the kidney dysfunction and structural abnormalities in the brain remains controversial. As for the opposite relationship, structural brain abnormalities, especially cerebral microbleeds and silent infarction, but not functional brain abnormalities, are associated with worse renal function. In addition, a higher UACR, but not a lower eGFR, was associated with a higher risk of Alzheimer's disease and vascular dementia.

Background Dementia is more prevalent among people with type 2 diabetes, but little is known regarding the influence of antidiabetic agents on this association. Objective This study assessed the impact of various antidiabetic agents on the risk of dementia among patients with Type 2 diabetes mellitus. Methods Relevant studies were retrieved from the PubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov databases. Nine antidiabetic agents were included in the search. Data were pooled via network meta-analysis and meta-analysis. Results Nine studies were selected for the network meta-analysis with 530,355 individuals and 17 studies for the meta-analysis with 1,258,879 individuals. The analysis excluded glucagon-like peptide 1 (GLP-1) analogs and sodium-dependent glucose transporter 2 (SGLT-2) inhibitors due to the absence of relevant data. The use of dipeptidyl peptidase-4 (DPP-4) inhibitors, metformin, thiazolidinedione, and sulfonylurea was associated with a decreased risk of dementia in comparison to no treatment with antidiabetic agents (hazard ratio [HR] for DPP-4 inhibitors, 0.54; 95% confidence interval [CI], 0.38–0.74, HR for metformin, 0.75; 95% CI, 0.63–0.86; HR for sulfonylurea, 0.85; 95%CI, 0.73–0.98 and HR for thiazolidinedione, 0.70; 95% CI, 0.55–0.89, respectively). However, the node-splitting analysis showed the inconsistency of direct and indirect estimates in sulfonylurea (P = 0.042). DPP-4 inhibitors, metformin, thiazolidinedione, and sulfonylurea exhibited a significant impact on the risk of dementia in diabetics compared with insulin (HR, 0.35; 95%CI, 0.20–0.59, HR, 0.48; 95% CI, 0.30–0.77, HR, 0.45; 95% CI, 0.29–0.73 and HR, 0.55; 95% CI, 0.34–0.88, respectively). DPP-4 inhibitors also exhibited a protective effect on the risk of Alzheimer's dementia compared with the no treatment with antidiabetic agents (HR, 0.48; 95% CI, 0.25–0.92). The meta-analysis demonstrated a protective effect of using metformin and DPP-4 inhibitors on the risk of dementia (HR, 0.86; 95% CI, 0.74–1.00 and HR, 0.65; 95% CI, 0.55–0.76, respectively). Further analysis showed insulin was associated with an increased risk of Alzheimer's dementia (HR, 1.60; 95% CI, 1.13–2.26). Only two case-control studies mentioned GLP-1 analogs and SGLT-2 inhibitors, and the pooled ORs showed no evidence of an association with dementia (GLP-1 analogs: 0.71; 95% CI, 0.46–1.10 and SGLT-2 inhibitors: 0.74; 95% CI, 0.47–1.15). Conclusion This analysis indicated that patients with type 2 diabetes under treatment with DPP-4 inhibitors presented with the lowest risk of dementia, followed by those treated with metformin and thiazolidinedione, while treatment with insulin was associated with the highest risk. For the increasing focus on the protective effect on dementia, further specific clinical studies are needed to evaluate the impact of GLP-1 analogs and SGLT-2 inhibitors on the risk of dementia.