Is the Pentagon-Copying Task More than a Cognitive Feature? Associations with Handgrip Strength, Gait Speed, and Frailty in Older Adults.

BACKGROUND: The pentagon copy is a sensitive item to the prediction of cognitive decline and dementia. Cognitive and physical/motor decline are able to accelerate the evolution of each other by representing a common pathway toward frailty. OBJECTIVES: The objective of the study was to investigate the association of the pentagon-copying task with physical and motor performances and with frailty, in a sample of older adults. METHOD: This observational, cross-sectional, and single-center study was conducted in a Geriatric Outpatients Clinic. Subjects aged ≥65 years were consecutively recruited, on a voluntary basis. Subjects with positive psychiatric history, with a severe neurocognitive disorder, with severe limitations on the upper limbs and/or reporting sensory deficits were excluded. The pentagon-copying task was scored from the Mini-Mental State Examination; the Qualitative Scoring Pentagon Test (QSPT) was also used. Handgrip strength was measured; a 46-item Frailty Index was calculated; in subjects with autonomous walking, a 4-meter gait speed was also measured. RESULTS: The study included 253 subjects (mean age 80.59 ± 6.89 years). Subjects making a wrong pentagon copy showed greater odds of exhibiting a strength deficit (OR = 3.57; p = 0.001) and of being frail (OR = 4.80; p < 0.001), and exhibited a slower gait. The QSTP score was significantly correlated with handgrip strength (r = 0.388) and gait speed (r = 0.188) and inversely correlated with frailty (r = -0.428); the QSTP score was significantly different between the quartiles of handgrip strength and frailty. CONCLUSIONS: The pentagon-copying task might also be confirmed as a quick screening tool of aging trajectories toward frailty by jointly evaluating cognitive and physical performances.

Reduced Levels of the Antiaging Hormone Klotho are Associated With Increased Aortic Stiffness in Diabetic Kidney Disease.

Introduction: Aortic pulse wave velocity (Ao-PWV) predicts cardiovascular and kidney disease in type 2 diabetes (T2D). Klotho is a circulating antiaging hormone (sKlotho) with putative cardiorenal protective effects. The relationship between sKlotho and Ao-PWV in diabetic kidney disease (DKD) is unknown. Methods: In a cross-sectional cohort study, the correlation of sKlotho measured by a validated immunoassay, and Ao-PWV measured by applanation tonometry, was investigated in 172 participants with T2D and early stage DKD (all had estimated glomerular filtration rate [eGFR] >45 ml/min) on stable renin angiotensin system (RAS) inhibition. In cultured human aortic smooth muscle cells (HASMCs) stimulated with angiotensin II (AngII), the effects of recombinant human sKlotho pretreatment were assessed on intracellular calcium ([Ca2+]i) responses and expression of proteins associated with proosteogenic HASMC phenotypes. Results: Mean (range) age of the cohort was 61.3 years (40-82) and 65% were male. Mean (±SD) Ao-PWV was 11.4 (±2.3) m/s, eGFR 78.8 (±23.5) and median (interquartile range) sKlotho of 358.5 (194.2-706.3) pg/ml. In multivariable linear regression analyses, we observed a statistically significant inverse relationship between sKlotho and Ao-PWV, which was independent of clinical risk factors for cardiorenal disease. Pretreatment of cultured HASMC with sKlotho significantly attenuated AngII-stimulated [Ca2+]i transients and reduced osteogenic collagen (Col1a2) expression. Conclusions: In individuals with T2D and early DKD, lower levels of sKlotho are associated with increased Ao-PWV. Taken together with the direct effect of sKlotho on mediators of aortic wall stiffness in vitro, these findings may explain the enhanced risk of cardiorenal disease in DKD.

GLP-1 Receptor Agonists in Obese Patients with Inflammatory Bowel Disease: from Molecular Mechanisms to Clinical Considerations and Practical Recommendations for Safe and Effective Use.

PURPOSE OF REVIEW: To discuss current literature and provide practical recommendations for the safe and effective use of glucagon-like peptide 1 receptor agonists (GLP-1 RA) in people with inflammatory bowel disease (IBD) and type 2 diabetes (T2D) and/or obesity. The molecular mechanisms that justify the potential benefits of GLP-1 RA in IBD and the links between IBD, obesity, and cardiovascular disease are also discussed. RECENT FINDINGS: Preliminary data suggest that GLP-1 RA can modulate crucial pathways in the pathogenesis of IBD, such as chronic inflammation circuits, intestinal tight junctions, and gut microbiome dysbiosis, setting the stage for human trials to investigate the role of these agents in the treatment of IBD among people with or without diabetes and obesity. However, gastrointestinal side effects related to GLP-1 RA need appropriate clinical management to mitigate risks and maximize the benefits of therapy in people with IBD. GLP-1 RA originally emerged as drugs for the treatment of hyperglycemia and are currently licensed for the management of T2D and/or overweight/obesity. However, their wealth of pleiotropic actions soon raised expectations that they might confer benefits on non-metabolic disorders. Future studies are expected to clarify whether GLP-1 RA deserve an adjunct place in the arsenal of drugs against IBD.

Postprandial Hypotension and Impaired Postprandial Sustained and Selective Attention in Older Inpatients: Is There a Link?

OBJECTIVES: The study aimed to investigate the prevalence of postprandial hypotension (PPH) in older inpatients, to verify the overall postprandial behavior of blood pressure and attentional performances, and to explore the overall associations between blood pressure (including PPH) and attentional performances. Eventually, we aimed to investigate differences on PPH, blood pressure values and attentional performances based on the subjects' frailty status. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: A sample of older inpatients at the Geriatric Unit of the University Hospital of Messina (Italy). METHODS: Basal, preprandial, and postprandial blood pressures (75 minutes after the meal) were measured for each patient; PPH was detected according to its empirical definition. Global cognitive functioning, and sustained and selective attention were assessed; a 46-item Frailty Index was calculated. RESULTS: The sample consisted of 112 inpatients (54 females), with a mean age of 80.9 years. The prevalence of PPH was 30.4%; in the postprandial window, a reduction in blood pressure between 10 and 20 mm Hg and a reduction of >20 mm Hg were reported by 27.1% and 29.9% of inpatients, respectively. In the postprandial evaluation, sustained and selective attention markedly decreased. No significant associations were found between PPH occurrence and the postprandial dip of attentional performances, and no significant cognitive differences were found between inpatients with and without PPH. On the other hand, reduced postprandial attentional performances were associated especially with preprandial lower systolic and diastolic blood pressure values. Ultimately, no significant differences in PPH occurrence were found between frail and nonfrail inpatients; frail inpatients significantly exhibited also an overall lower cognitive functioning. CONCLUSIONS AND IMPLICATIONS: In our sample, PPH and impaired postprandial attentional performances were not associated, even though this association deserves further investigation. In hospitalized older adults, the accurate management of blood pressure levels appears relevant, because we evidenced that low blood pressure (especially preprandial) was associated with poor attentional functioning. Although the plausible occurrence of several interfering and confounder factors was observed in an acute care setting, we consider that the screening of attentional functioning among hospitalized older patients could be helpful.

Effect of active vitamin-D on left ventricular mass index: Results of a randomized controlled trial in type 2 diabetes and chronic kidney disease.

BACKGROUND: Active vitamin-D deficiency is a potential modifiable risk factor for increased ventricular mass. We explored the effects of active vitamin-D (calcitriol) treatment on left ventricular mass in patients with type-2 diabetes (T2D) and chronic kidney disease (CKD). METHODS: We performed a 48-week duration single center randomized double-blind parallel group trial examining the impact of calcitriol, 0.5 mcg once daily, as compared to placebo on a primary endpoint of change from baseline in left ventricular mass index (LVMI) measured by magnetic resonance imaging . Patients with T2D, CKD stage-3 and raised left ventricular mass on stable renin angiotensin aldosterone system blockade, who all had elevated intact parathyroid hormone were eligible. Secondary endpoints included interstitial myocardial fibrosis, assessed with cardiac magnetic resonance imaging. In total, 45 (male 73%) patients with T2D and stage-3 CKD were studied (calcitriol n = 19, placebo n = 26). RESULTS: Following 48-weeks calcitriol treatment, the median difference and the (95% CI) of LVMI between the 2 treatment arms was 1.84 (-1.28, 4.96), similar between the 2 groups studied. Intact parathyroid hormone fell only in the calcitriol group from 142 pg/mL (80-293) to 76 pg/mL (41-204)(median, interquartile range, P= .04). No significant differences were observed in interstitial myocardial fibrosis or other secondary endpoints. CONCLUSIONS: The study did not provide evidence that treatment with calcitriol as compared to placebo might improve LVMI in patients with T2D, mild left ventricular hypertrophy and stable CKD. Our data does not support the routine use of active vitamin-D for LVMI regression and cardiovascular protection in patients with T2D and stage-3 CKD.

Is the relationship between erythropoiesis and renal function one of the secrets of extreme longevity?

BACKGROUND AND AIMS: Renal function and erythropoiesis could be impaired with advancing age. Neutrophil gelatinase-associated lipocalin (NGAL) as well as erythropoietin (EPO) levels are two useful biomarkers of the renal status. In advanced age, the relationships between NGAL, EPO and hemoglobin (Hb) levels remains unknown. The aim of the present study is to evaluate the relationship between renal function and erythropoiesis in a small cohort of centenarians. METHODS AND RESULTS: We observed thirty-one healthy centenarians with normal hemoglobin levels, a mild reduction in eGFR and no need of erythropoiesis support. We found a significant inverse association between NGAL and GFR, hemoglobin levels and EPO, confirming the key role of the renal function on erythropoiesis also in extreme longevity. A gender difference emerged, showing female participants with lower eGFR and Hb values more than males. CONCLUSIONS: Our findings suggested a new link between renal function, erythropoiesis and longevity in centenarians and these could have relevant implications in clinical practice. These findings could explain why very old subjects presenting a slight GFR reduction seemed not to be exposed to a significant risk of mortality.

Impact of treatment with active vitamin D calcitriol on bone turnover markers in people with type 2 diabetes and stage 3 chronic kidney disease.

People with diabetes and chronic kidney disease (CKD) are predisposed to bone mineral disorders and increased fracture risk. There is limited data on the effect of calcitriol on bone turnover markers (BTMs) in people with type 2 diabetes (T2DM) and stage 3 CKD. In a pre-specified secondary endpoint analysis of a 48-week randomized placebo controlled double-blind trial, we studied the effects of oral calcitriol 0.25 µg once daily on circulating BTMs that included osteocalcin (OCN), C-terminal telopeptide of type I collagen (CTXI), procollagen type I N-propeptide (PINP) and fibroblast growth factor-23 (FGF-23). Inclusion criteria were people with T2DM with stable stage 3 CKD stage and intact parathyroid hormone (iPTH) >30 pg/ml. In total, 127 people [calcitriol (n = 64), placebo (n = 63)] were eligible for analyses. Baseline median (interquartile range) age of the cohort was 67 (60.5-70) years, iPTH (median range) 73.9 (55, 105) pg/ml and eGFR 40 (33, 48.5) ml/min. Calcitriol treatments resulted in a significant fall in iPTH, CTX, PINP and OCN levels and rise FGF-23, with mean (95 % confidence interval) between group differences in iPTH [-27.8 pg/ml; 95 % CI (-42.3 to -13.2); p < 0.001], FGF-23 [30.6 pg/ml; 95 % CI (14.8 to 46.3); p < 0.001], CTX [0.12 µg/l; 95 % CI (-0.19 to -0.06); (p < 0.001) and OCN [-4.03 ng/ml; 95 % CI (-7.8 to -0.27); p = 0.036]. Similarly we observed with calcitriol, as between treatment percentage change, a reduction of -38 % for iPTH, -34 % for CTX, and -28 % for OCN levels respectively (p < 0.05 for all). In people with T2DM and stage 3 CKD, calcitriol reduces the levels of CTX, OCN, PINP and iPTH. Further studies are needed to assess the clinical significance of our findings and the related long term impact on bone health.

Effect of calcitriol treatment on arterial stiffness in people with type 2 diabetes and stage 3 chronic kidney disease.

AIMS: Active vitamin D deficiency is associated with increased aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD. METHODS: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV. People with T2DM and stable stage 3 CKD with intact parathyroid hormone (iPTH) level >30 pg/mL were eligible. RESULTS: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, mean ± standard deviation (SD), in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001. CONCLUSION: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.

Can sodium-glucose cotransporter 2 inhibitors 'spin the thread of life'?

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were first used as antidiabetic agents that lower the blood glucose levels by promoting glycosuria. In recent years, randomised clinical trials have demonstrated that SGLT2i reduce cardiovascular-renal events and all-cause mortality in people with and without diabetes. The cardio-renal benefits observed are independent of glucose lowering effect and multiple mechanisms have been proposed for these results. SGLT2i can exert anti-ageing effects on the vasculature and other body organs through several signalling pathways including the activation of the nuclear factor erythroid-2-related factor 2 and the induction of antioxidant enzymes. We speculate that the pro-longevity effects of the SGLT2i are mediated by soluble Klotho, an anti-ageing kidney-derived hormone and an emerging therapeutic target for cardio-renal diseases.

Does Dapagliflozin influence arterial stiffness and levels of circulating anti-aging hormone soluble Klotho in people with type 2 diabetes and kidney disease? Results of a randomized parallel group clinical trial.

Objective: The mechanisms that explain the cardio-renal benefits of sodium glucose co-transporter 2 (SGLT-2) inhibitors are unknown. The effect of SGLT-2 inhibitors on arterial aging, measured by Aortic Pulse Wave Velocity (Ao-PWV) and Soluble Klotho (s-Klotho), a circulating anti-aging biomarker of arterial health are also unclear. Design/Setting: A 24-week single center randomized controlled trial (registry number/ EudraCT Number: 2013-004042-42) comparing Dapagliflozin and Ramipril (D+R) versus Ramipril (R) on the primary endpoint of urine albumin excretion rate (AER) and pre-specified secondary endpoints of Ao-PWV and biomarkers of arterial aging [s-Klotho and Fibroblast Growth Factor 23 (FGF-23)]. People with type 2 diabetes who had estimated glomerular filtration rate (eGFR) > 60 ml/min and residual microalbuminuria on maximum tolerated renin angiotensin system (RAS) inhibition were included in this study. Results: In total, 33 participants (male 73%) were randomized to either D+R (n = 17) or R (n = 16) arms. After 24 weeks of treatment, Ao-PWV (mean ± SD) did not change significantly from baseline D +R [9.06 ± 1.91 m/s to 9.13 ± 2.03 m/s], and R [9.88 ± 2.12 m/s to 10.0 ± 1.84 m/s]. AER fell significantly by 43.5% (95% CI: -57.36%, -29.56%; p < 0.01) in people in the D+ R arm only. We do not observe any significant changes in FGF-23 or s-Klotho. HbA1c and Angiotensin 1-7 fell significantly only in D + R arm. Conclusions: The combination of Dapagliflozin and Ramipril had no effects on Ao-PWV and s-Klotho which are biomarkers of arterial aging and cardio-renal risk. Our data suggest that the early cardio-renal benefits observed with SGLT-2 inhibitors are unlikely to be related to an improvement in arterial aging.

International Survey on Frailty Assessment in Patients with Cancer.

BACKGROUND: Frailty negatively affects the outcomes of patients with cancer, and its assessment might vary widely in the real world. The objective of this study was to explore awareness and use of frailty screening tools among the ONCOassist healthcare professionals (HCPs) users. MATERIALS AND METHODS: We sent 2 emails with a cross-sectional 15-item survey in a 3-week interval between April and May 2021. Differences in the awareness and use of tools according to respondents' continents, country income, and job types were investigated. RESULTS: Seven hundred thirty-seven HCPs from 91 countries (81% physicians, 13% nurses, and 5% other HCPs) completed the survey. Three hundred and eighty-five (52%) reported assessing all or the majority of their patients; 518 (70%) at baseline and before starting a new treatment. Three hundred and four (43%) HCPs were aware of performance status (PS) scores only, 309 (42%) age/frailty/comorbidity (AFC) screening, and 102 (14%) chemotoxicity predictive tools. Five hundred and thirty-seven (73%) reported using tools; 423 (57%) just PS, 237 (32%) AFC, and 60 (8%) chemotoxicity ones. Reasons for tools non-use (485 responders) were awareness (70%), time constraints (28%), and uselessness (2%). There were significant differences in awareness and use of screening tools among different continents, country income, job types, and medical specialties (P < .001 for all comparisons). CONCLUSION: Among selected oncology HCPs, there is still a worldwide lack of knowledge and usage of frailty screening tools, which may differ according to their geography, country income, and education. Targeted initiatives to raise awareness and education are needed to implement frailty assessment in managing patients with cancer.

Ageing well with diabetes: A workshop to co-design research recommendations for improving the diabetes care of older people.

AIMS: To identify key research questions where answers could improve care for older people living with diabetes (PLWD), and provide detailed recommendations for researchers and research funders on how best to address them. METHODS: A series of online research workshops were conducted, bringing together a range of PLWD and an acknowledged group of academic and clinical experts in their diabetes care to identify areas for future research. Throughout the pre-workshop phase, during each workshop, and in manuscript preparation and editing, PLWD played an active and dynamic role in discussions as part of both an iterative and narrative process. RESULTS: The following key questions in this field were identified, and research recommendations for each were developed: How can we improve our understanding of the characteristics of older people living with diabetes (PLWD) and their outcomes, and can this deliver better person-centred care? How are services to care for older PLWD currently delivered, both for their diabetes and other conditions? How can we optimise and streamline the process and ensure everyone gets the best care, tailored to their individual needs? What tools might be used to evaluate the level of understanding of diabetes in the older population amongst non-specialist Healthcare Professionals (HCPs)? How can virtual experts or centres most effectively provide access to specialist multi-disciplinary team (MDT) expertise for older PLWD and the HCPs caring for them? Is a combination of exercise and a nutrition-dense, high protein diet effective in the prevention of the adverse effects of type 2 diabetes and deterioration in frailty, and how might this be delivered in a way which is acceptable to people with type 2 diabetes? How might we best use continuous glucose monitoring (CGM) in older people and, for those who require support, how should the data be shared? How can older PLWD be better empowered to manage their diabetes in their own home, particularly when living with additional long-term conditions? What are the benefits of models of peer support for older PLWD, both when living independently and when in care? CONCLUSIONS: This paper outlines recommendations supported by PLWD through which new research could improve their diabetes care and calls on the research community and funders to address them in future research programmes and strategies.