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Notably, both the renal and cerebral microcirculations share common characteristics of high flow and low resistance ( Indeed, the manifestations of cerebral small vessel disease (cSVD), including lacunar infarcts, white matter hyperintensities (WMH), and brain atrophy, bear similarities to diabetic microvascular complications, such as DKD ( 2.2 Renin-angiotensin-aldosterone system and cognitive impairment The brain renin-angiotensin-aldosterone system (RAAS) plays a vital role in neural function homeostasis and normal cognitive function, including memory, consolidation, and information retrieval ( Notably, enhanced activation of angiotensin II type 1 receptor by angiotensin II and the mineralocorticoid receptor by glucocorticoids and aldosterone can increase blood-brain barrier (BBB) permeability, induce oxidative stress, neuroinflammation, and astrocyte dysfunction ( Figure 2 ), while also decreasing cerebral blood flow ( Figure 2 3 The relationship between renal dysfunction and cognitive impairment 3.1 Correlation of renal damage with cognitive decline Chronic renal injury is primarily characterized by albuminuria and/or a low eGFR, and it is strongly linked to diabetes ( Despite variations in methodologies and outcome assessments, several studies have established associations between albuminuria and the risk of developing cognitive impairment and dementia, as well as correlations with imaging markers for cognitive decline

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The authors reported that AOD-9604 stimulated lipolysis in isolated adipocytes and that chronic daily treatment in obese Zucker rats produced reductions in body weight gain of more than 50% relative to untreated controls over the treatment period, without effects on insulin sensitivity or IGF-1 levels [3]