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Background Fluid imbalance is associated with various clinical conditions, but the association between elevated extracellular‐water to total‐body‐water (ECW/TBW) ratio, an indicator of fluid balance, and cognitive impairment is unknown. We aimed to investigate relationship between ECW/TBW ratio and cognitive function in type 2 diabetes mellitus. Methods This study was a cross‐sectional design, comparing 1233 patients aged 61.4 ± 8.0 years from the Singapore Study of Macro‐angiopathy and Micro‐vascular Reactivity in Type 2 Diabetes (SMART2D) cohort. ECW/TBW was measured using bioelectrical impedance method. Cognitive function was assessed with Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Multiple linear regression was used to examine association between ECW/TBW and RBANS scores, adjusting for demographics, education, clinical covariates, and apolipoprotein E allele. Results In unadjusted analyses, there was an inverse dose‐dependent association between ECW/TBW and RBANS total score. The associations persisted in fully adjusted model with β = −1.18 (95% confidence interval [CI] −2.19 to −0.17; P = 0.022) for slight edema and −2.33 (−3.99 to −0.67; P = 0.006) for edema. Slight edema and edema were significantly associated with reduced cognitive function in delayed memory and attention. There was significant association between edema but not slight edema, with reduced cognitive function in language. Pulse pressure accounted for 16.8% of association between ECW/TBW and RBANS total score. Conclusions Our novel finding of an independent association between higher ECW/TBW and poorer cognitive function highlights the potential importance of maintaining body fluid balance in the management of cognitive impairment.

Lower extremity skeletal muscle mass (LESM) in Type 2 Diabetes (T2D) has been linked to adverse clinical events, but it is not known whether it is associated with cognitive difficulties. We conducted a cross-sectional study on 1,235 people (mean age 61.4 ± 8.0 years) with T2D under primary and secondary care in Singapore. Bioelectrical impedance analyses (BIA) measures of upper extremity skeletal muscle mass (UESM), LESM and appendicular skeletal muscle index (SMI) were related to the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) measures of cognition, in multiple linear regression. In multivariable models, tertile 1 LESM (b = −2.62 (−3.92 to −1.32)) and tertile 2 LESM (b = −1.73 (−2.73 to −0.73)), referenced to tertile 3) were significantly associated with decreased RBANS total score. Significant associations of LESM with cognitive domain performances were observed for tertile 1 (b = −3.75 (−5.98 to −1.52)) and tertile 2 (b = −1.98 (−3.69 to −0.27)) with immediate memory, and for tertile 1 (b = −3.05 (−4.86 to −1.24)) and tertile 2 (b = −1.87 (−3.25 to −0.48)) with delayed memory, and for tertile 1 (b = −2.99 (−5.30 to −0.68)) with visuospatial/ constructional ability. Tertile 1 SMI (b = −1.94 (−3.79 to −0.08) and tertile 2 SMI (b = −1.75 (−3.14 to −0.37)) were also associated with delayed memory. There were no associations between UESM with cognitive performance. Lower LESM may be a useful marker of possible co-occuring cognitive dysfunction. Sarcopenia, the age-related decline in skeletal muscle mass and strength and physical function 1,2 , is linked to adverse events and outcomes including hospitalization, disability and mortality 3-6. Recent studies have also examined the association between sarcopenia and impaired cognitive function as both conditions are highly prevalent in advanced age 2. However, results have been rather divergent 7-12 as some studies reported a link 9-11 while others did not 7,8,12. It is not clear if such a relationship is evident in older individuals with diabetes. Of note, older patients with long-term type 2 diabetes (T2D) typically show accelerated loss of muscle mass and strength. As skeletal muscle plays a key role in glucose storage, absorption and metabolism, diabetic myopathy is an important, but often overlooked condition, that contributes to additional complications and adverse outcomes 13. It is plausible that sarcopenia and cognitive impairment may have a "common soil" known as age-related inflammation (i.e.

Background: The association between sodium-glucose cotransporter-2 inhibitors (SGLT2i) use and cognitive function in type 2 diabetes remains unclear. Objective: Explore the association between SGLT2i and longitudinal changes in cognitive function in adults with type 2 diabetes (T2DM) and assessed the cognitive domains which were impacted by SGLT2i. Methods: We conducted a prospective cohort study of 476 patients aged 60.6±7.4 years with follow-up period up to 6.4 years. Data on SGLT2i use was derived from questionnaire and verified with clinical database. We used Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to assess cognition. The association between SGLT2i use and rate of RBANS score change was examined using multiple linear regression. Results: There were 138 patients (29.0%) on SGLT2i, including 84 (17.7%) for <  3 years and 54 (11.3%) for ≥3 years. SGLT2i use was positively associated with RBANS total score increase in language (coefficient 0.60; 95% CI 0.10–1.11; p = 0.019) in unadjusted analysis. This positive association persisted in fully adjusted model (coefficient 0.74; 95% CI 0.12 to 1.36; p = 0.019). SGLT2i use for ≥3 years was positively associated with RBANS score increase globally and in language domain in fully adjusted analysis with coefficients 0.54 (95% CI 0.13 to 0.95; p = 0.010) and 1.12 (95% CI 0.27 to 1.97; p = 0.010) respectively. Conclusion: Our findings revealed a previously unobserved association between ≥3 years SGLT2i use and improved cognitive scores globally and in language domain and executive function. Future studies should investigate the role of SGLT2i in ameliorating cognitive decline.