Factors associated with cognitive impairment in people with diabetes-related foot ulcers: a systematic review

Abstract

Diabetes-related foot ulcers (DFUs) are common and serious complications of diabetes mellitus, and recent evidence indicates a potential association between DFUs and the development of cognitive impairment. However, no comprehensive review has been conducted to investigate the true associations between DFUs and cognition. Therefore, this systematic review aimed to investigate the factors contributing to cognitive impairment in people with DFUs. This review was conducted in accordance with the PRISMA guidelines. MEDLINE via EBSCOhost, PubMed, CINAHL, EMBASE, and PsycINFO databases were searched from inception to June 2025 for studies assessing cognition in people with DFUs. All observational study designs were included. Results were independently screened for eligibility by two reviewers. Included studies were assessed for methodological quality using the Mixed Methods Appraisal Tool, and data were extracted using a customised data extraction tool by two reviewers. The database search identified 460 records, of which 317 were screened, and four studies were included. All studies were conducted in single centres. Three were two case-control studies, and two cross-sectional studies. None of the studies reported risk factors for cognitive impairment. Among these associated factors, 14 were identified in bivariate analyses, and those are remained significant in multivariate analyses in at least one of the included studies, such as socio-demographic factors (age, sex, education), lifestyle factors (smoking, BMI, depression), diabetes-specific factors (HbA1c, duration of diabetes), comorbidities (cardiovascular, cerebrovascular, nephropathy, retinopathy) and foot-related complications (peripheral neuropathy, amputation). No meta-analysis was conducted due to the heterogeneity of the included studies. Although no studies specifically identified risk factors, this review suggests that multiple factors, including sociodemographic, lifestyle, diabetes-related, comorbidities, and foot-related complications, are associated with cognitive impairment in people with DFUs. To establish a robust relationship between cognition and DFUs, these associated factors need to be considered in future studies. Furthermore, more rigorous cohort studies are warranted to identify risk factors for cognitive impairment in this population.