Diabetic foot ulcers as markers of systemic disease burden: Associations with cognitive impairment in type 2 diabetes—A case-control cross-sectional study

Background Type 2 diabetes mellitus (T2DM) confers increased risk of cognitive decline and Alzheimer's disease (AD), driven by chronic metabolic dysregulation, microvascular injury, and systemic inflammation. Diabetic foot ulcers (DFUs), a severe complication of T2DM, reflect advanced systemic burden, yet their neurocognitive consequences remain insufficiently characterized. Objective To evaluate domain-specific cognitive functioning in adults with DFUs compared with matched healthy controls using an AD-focused cognitive assessment battery, and to examine associations with depressive symptoms and health-related quality of life (HRQoL). Methods In this cross-sectional case–control study, 22 adults with T2DM and DFUs and 22 age- and gender-matched healthy controls completed the Addenbrooke's Cognitive Examination III, Trail Making Test, and Weigl Colour Form Sorting Test. Comorbidity burden, depressive symptoms (PHQ-9), and HRQoL (EQ-5D-5L) were recorded. Adjusted odds of domain-specific cognitive impairment were estimated using Generalized Linear Models. Results DFU participants showed significantly poorer performance across multiple cognitive domains, including verbal fluency, visuospatial ability, memory, and executive function. Independent neuropsychological tests corroborated slowed processing speed and reduced cognitive flexibility. DFU status was associated with more than a threefold increase in odds of impairment in fluency and visuospatial domains. The DFU participants also demonstrated markedly poorer HRQoL, higher depressive symptoms, and greater comorbidity burden. Conclusions DFUs are associated with a more severe and domain-specific neurocognitive profile than typically observed in T2DM alone, affecting functions highly relevant to early AD vulnerability. These findings suggest that DFUs may identify a subgroup at heightened risk of neurodegenerative trajectories, supporting the need for biomarker-informed longitudinal investigations.