Background Extracellular water-to-total body water (ECW/TBW) ratio reflects volume overload. It promotes aortic stiffness which predicts Alzheimer's disease and related dementias (ADRD) development. Objective We studied longitudinal relationship between ECW/TBW ratio and neurocognitive decrements in type 2 diabetes (T2D) and mediating role of aortic stiffness. Methods In a prospective Asian cohort, we measured ECW/TBW ratio using bioimpedance analysis (BIA) and pulse wave velocity (PWV) using applanation method. The Repeatable Battery for Assessment of Neuropsychological Status (RBANS) was used to assess neurocognitive performance. Linear mixed model was applied to examine if ECW/TBW was associated with neurocognitive performance Results The study comprised 1412 patients at baseline. Over maximum of 9.4 years’ follow-up, 823 patients had repeated neurocognitive assessment. We observed associations between higher ECW/TBW ratio (continuous variable) and edema group with lower total RBANS score. The adjusted coefficients were −1.43 (95%CI −2.31, −0.56) and −5.88 (95%CI −9.00, −2.75) respectively. There were similar observations for delayed memory, visuospatial/constructional and attention. Based on cross-lagged panel model, there was larger standardized effect size from baseline ECW/TBW ratio to follow-up total RBANS score (β = 0.053, p = 0.026) compared to that from baseline total RBANS score to follow-up ECW/TBW ratio (β = −0.020, p = 0.461). PWV mediated 13.3% of the relationship. Conclusions Our results demonstrated a relationship between volume overload and cognitive decrements, with potential mediation from aortic stiffness. There was temporal precedence of ECW/TBW over neurocognitive performance. BIA-determined ECW/TBW ratio is a promising biomarker of neurocognitive decrements in T2D.
Low et al. (Sun,) studied this question.