The renin-angiotensin system (RAS) is involved in the pathogenesis of insulin sensitivity (IS). The role of RAS in insulin resistance and muscular circulation has yet to be elucidated. Therefore, this study sought to determine the mechanisms of angiotensin II receptor blockers (ARBs) and/or diuretics on IS and capillary density (CD) in fructose-fed rats (FFRs). Sprague-Dawley rats were fed either normal chow (control group) or fructose-rich chow for 8 weeks. For the last 4 weeks, FFRs were allocated to four groups: an FFR group and groups treated with the thiazide diuretic hydrochlorothiazide (HCTZ), with the ARB losartan, or both. IS was evaluated by the euglycemic hyperinsulinemic glucose clamp technique at week 8. In addition, CD in the extensor digitorum longus muscle was evaluated. Blood pressure was significantly higher in the FFRs than in the controls. HCTZ, losartan and their combination significantly lowered blood pressure. IS was significantly lower in the FFR group than in the controls and was even lower in the HCTZ group. Losartan alone or combined with HCTZ significantly increased IS. In all cases, IS was associated with muscular CD, but not with plasma adiponectin or lipids. These results indicate that losartan reverses HCTZ-exacerbated insulin resistance, which can be mediated through the modulation of muscular circulation in rats with impaired glucose metabolism.

As the older population increases, the need for early detection of cognitive decline is also increasing. In this study, we examined whether our paper-pencil type group examination for cognitive assessment (PAPLICA) could detect the effects of years of education and aging.

Diabetic kidney disease is a major cause of renal failure that urgently necessitates a breakthrough in disease management. Here we show using untargeted metabolomics that levels of phenyl sulfate, a gut microbiota-derived metabolite, increase with the progression of diabetes in rats overexpressing human uremic toxin transporter SLCO4C1 in the kidney, and are decreased in rats with limited proteinuria. In experimental models of diabetes, phenyl sulfate administration induces albuminuria and podocyte damage. In a diabetic patient cohort, phenyl sulfate levels significantly correlate with basal and predicted 2-year progression of albuminuria in patients with microalbuminuria. Inhibition of tyrosine phenol-lyase, a bacterial enzyme responsible for the synthesis of phenol from dietary tyrosine before it is metabolized into phenyl sulfate in the liver, reduces albuminuria in diabetic mice. Together, our results suggest that phenyl sulfate contributes to albuminuria and could be used as a disease marker and future therapeutic target in diabetic kidney disease.

Background: To delay cognitive decline, it is important to engage actively in preventive activities from middle age (50-64 years of age). We have developed a cognitive intervention program using picture book reading, and demonstrated that it is effective for improving memory in older adults. However, the effect of the intervention on memory and other cognitive functions in middle-aged people has not been examined. The current study investigated the effects of the picture book reading program on cognitive function in middle-aged people. Methods: This single-blind (examiners were blinded) randomized controlled trial was conducted in Tokyo, Japan. A total of 65 participants were randomly assigned to the intervention group (IG) (n = 32), in which members attended 12 picture book reading classes held once a week, or the active control group (CG) (n = 33), in which members received lectures on health maintenance. Cognitive tests were conducted before and after the intervention. The primary outcome was memory, and the secondary outcomes were verbal function and executive function. Results: The results showed that there was no significant difference between the IG and the CG in change scores (post minus pre) for memory. On the other hand, there was a significant difference in change scores of the category fluency, which is a measure of verbal function, suggesting improvements in IG compared to CG. There were also no significant differences in executive function. Conclusions: The results indicated that our previous finding of an improvement in memory function in older adults was not found in middle-aged people. However, the findings suggest that the picture book reading program may affect lexical access ability in verbal function among middle-aged people. Because maintaining verbal function is important for daily communication, these findings suggest that this program may be a useful countermeasure for cognitive decline in middle-aged people. Clinical Trial Registration: University Hospital Medical Information Network Clinical Trial Registry, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048012, Identifier: UMIN 000042071.

Frequent engagement in intellectual activities has been shown to reduce the risk of developing dementia. The present study sought to examine the association between the frequency of daily intellectual activities and cognitive domains in older adults with complaints of forgetfulness.

An association between cognitive impairment and tripping over obstacles during locomotion in older adults has been suggested. However, owing to its memory-guided movement, whether this is more pronounced in the trailing limb is poorly known. We examined age-related changes in stepping over, focusing on trailing limb movements, and their association with cognitive performance. Age-related changes in obstacle avoidance were examined by comparing the foot kinematics of 105 older and 103 younger adults when stepping over an obstacle. The difference in the clearance between the leading and trailing limbs (Δ clearance) was calculated to determine the degree of decrement in the clearance of the trailing limb. A cognitive test battery was used to evaluate cognitive function among older adults to assess their association with Δ clearance. Older adults showed a significantly lower clearance of the trailing limb than young adults, resulting in greater Δ clearance. Significant correlations were observed between greater Δ clearance and scores on the Montreal Cognitive Assessment and immediate recall of the Wechsler Memory Scale-Revised Logical Memory test. Therefore, memory functions may contribute to the control of trailing limb movements, which can secure a safety margin to avoid stumbling over an obstacle during obstacle avoidance locomotion.

The purpose of this study is to clarify the influence of social interaction on the effect of a cognitive intervention program using Go.

Deterioration of hand motor function is a possible risk factor of cognitive impairment in older adults. Despite a growing body of research, a lack of clarity exists regarding the relationships. This review offers a synthesis of existing observational studies evaluating the associations of handgrip strength and hand dexterity with cognitive performance in community-dwelling older adults.