Hyperinsulinemia, insulin resistance and cognitive decline in older cohort.

OBJECTIVE: Type 2 diabetes has been recently recognized as an important risk factor for cognitive decline of patients with Alzheimer's disease (AD). But the roles of hyperinsulinemia (HI) and insulin resistance (IR) in the development of AD are still controversial. This study was designed to evaluate whether HI or IR influenced the cognitive functions of older cohort. METHODS: The cognitive functions of 328 consecutive elderly patients were evaluated with a battery of cognitive rating scales. Their fasting blood glucose (FBG) and fasting insulin (FINS) were analyzed and IR was calculated with modified-Homa. The cognitive scores in different groups and the correlation of cognitive functions with HI or IR were analyzed. RESULTS: In our study, there were 180 participants with HI and 148 without HI, and 192 with IR and 136 without IR. The participants with HI showed worse cognitive functions than those without HI in MMSE, MOCA, CDR, orientation, delayed memory, and attention/calculation domains. Similarly, the elderly with IR had lower cognitive scores than those without IR in MMSE, MOCA, CDR, GDS, orientation, delayed memory, and attention/calculation domains. The insulin levels and Homa IR had negative correlation with the scores of MMSE and delayed memory, not only in the model 1 adjusted for FBG and diabetes history, but also in the model 2 adjusted for all nine demographic characteristics. CONCLUSION: HI and IR are important risk factors for cognitive decline of the elderly, especially for the dysfunctions in delayed memory domains.

The relationship between glucose excursion and cognitive function in aged type 2 diabetes patients.

OBJECTIVE: Evidence suggests that type 2 diabetes (T2DM) is associated with an increased risk of dementia and that glucose variability is an independent risk factor for diabetic complications. This study investigated the relationship between glucose excursion and cognitive function in aged T2DM patients. METHODS: A total of 248 aged T2DM patients wore a continuous glucose monitoring system (CGMS) for 3 days in order to evaluate glucose excursion, including mean amplitude of glycemic excursions (MAGE) and mean of daily difference (MODD). All subjects were evaluated with a number of accepted cognitive function tests, including the mini-mental status examination (MMSE). The relationship between MAGE and MODD and performance on these cognitive tests was assessed. RESULTS: The MAGE and MMSE score were negatively correlated, likewise with the correlation between MODD and MMSE. Liner multivariate regression analysis showed that MAGE and MODD were also negatively related to MMSE independent of age, sex, glycemic control, hypertension, smoking, or coronary heart disease history. CONCLUSION: Glucose excursion is related to cognitive function in aged T2DM patients. Elevated glucose excursion decreased the MMSE score, which reflects general cognitive function. Thus, therapy aimed at controlling glucose excursion may be beneficial for maintaining cognitive function in aged T2DM patients.

Platelet glycoprotein IIIa gene polymorphism (Leu33Pro) and aspirin resistance in a very elderly Chinese population.

OBJECTIVES: To study the relationship between platelet glycoprotein IIIa gene (GP IIIa) polymorphism (Leu33Pro) and aspirin resistance in a very elderly Chinese population. METHODS: Four hundred fifty very elderly Chinese people receiving aspirin therapy were enrolled in the study. Patients who underwent arachnoid acid-induced platelet aggregation were then divided into two groups based on their resistance to aspirin: aspirin-resistant (AR) group (n=236) and aspirin-sensitive (AS) group (n=214). The Leu33Pro polymorphism of the GP IIIa gene was scanned by polymerase chain reaction-restriction fragment-length polymorphism. RESULTS: In the AR group, 224 participants had the A1/A1 genotype and 12 had the A1/A2 genotype. All patients in the AS group had the A1/A1 genotype. Thus, there was significant difference between these two groups in the genotype distribution (p<0.05). CONCLUSION: The genetic polymorphism of the GP IIIa gene was associated with AR in a very elderly Chinese population.

Epigenetic suppression of hippocampal BDNF mediates the memory deficiency induced by amyloid fibrils.

Accumulating evidences demonstrated that epigenetic modification of the expression of specific genes contributed to the pathogenesis of neurological disorders with dementia, including Alzheimer's disease (AD). Emerging reports also found the reduction of hippocampal brain-derived neurotrophic factor (BDNF) in the patients and rodent models of AD, while the mechanism and functional significance remain debated. The present study aims to study the epigenetic mechanism underlying the BDNF reduction and its functional significance in the rats with hippocampal infusion of amyloid fibrils. In the rats injected with amyloid fibrils, significant decreases of BDNF expression and the mRNA of Bdnf exon VI were found in the hippocampal CA1 area. Significantly increased hippocampal HDAC2 expression and its occupancy in the promoter region of Bdnf exon VI were also observed, thus contributing to the histone H3 deacetylation and BDNF suppression in the hippocampal CA1 in the rats injected with amyloid fibrils. Inhibition of HDAC2 activity by trichostatin A substantially recovered the histone H3 acetylation in the promoter region of Bdnf exon VI and BDNF expression, thus mitigating the synaptic dysfunction and memory deficiency induced by amyloid fibrils. These results elucidate the epigenetic mechanism underlying the BDNF reduction induced by amyloid fibrils, and provided novel insights into the pathogenic mechanism of Alzheimer's disease.

Alprostadil plays a protective role in contrast-induced nephropathy in the elderly.

PURPOSE: To evaluate the protective effects of alprostadil on contrast-induced nephropathy (CIN) in elderly patients. METHODS: We randomized 370 patients into the control or alprostadil group. The patients in the control group were injected with 100 ml sterile saline and the patients in the alprostadil group with alprostadil (0.4 µg/kg/day) in 100 ml sterile saline before and after iohexol-enhanced (100 ml) computed tomography (CT). Serum creatinine (Scr), blood urea nitrogen (BUN), cystatin C (CysC), and creatinine clearance (Ccr) were analyzed or calculated. ΔScr and ΔCysC were determined by the changes between baseline and highest Scr and CysC levels. The standard for CIN was a postdose Scr increase >44.2 µmol/l or >25 % over baseline. RESULTS: In the control group, peak Scr (P < 0.05) and ΔScr (P < 0.01) were higher than those in the alprostadil group. The postdose CysC at 24 h (P < 0.05), 48 h (P < 0.05), and 72 h (P < 0.05), peak CysC (P < 0.01), and ΔCysC (P < 0.05) in the control group were higher than those in the alprostadil group. The incidence of CIN in the control group was 22.2 %, which was higher than in the alprostadil group (9.1 %, P < 0.01). Subgroup analyses in patients with advanced age (≥ 80 years), concomitant hypertension or diabetes, and abnormal baseline renal function (Ccr ≤ 60 ml/min) showed that the alprostadil group had lower ΔScr and ΔCysC than the control group after contrast-enhanced CT examination in all four subgroups (P < 0.05 or P < 0.01). CONCLUSIONS: In this cohort of older patients undergoing contrast CT, the use of alprostadil reduced the incidence of CIN.

Effects of telmisartan on insulin resistance and visceral fat distribution in Chinese hypertensive patients with obesity.

OBJECTIVE: To investigate the effects of telmisartan on body fat distribution and insulin sensitivity in patients with hypertension and obesity. METHODS: In this prospective, randomized study, outpatients from the Sixth People's Hospital affiliated to Shanghai Jiaotong University, Shanghai, China were treated with telmisartan (n=23), or losartan (n=22) for 16 weeks between December 2009 to January 2011. Parameters such as waist and hip circumference, body mass index, fasting blood glucose, insulin, lipids, serum adiponectin, and tumor necrosis factor-alpha (TNF-alpha) were measured before and after treatment. The abdominal visceral fat area (VFA) and subcutaneous fat area (SFA) were determined by magnetic resonance imaging. Insulin sensitivity was estimated by homeostasis model assessment (HOMA-IR). RESULTS: Compared with baseline, the systolic and diastolic blood pressure decreased significantly in both groups. However, the levels of HOMA-IR, serum adiponectin, and TNF-alpha only improved in the telmisartan group. Similarly, the VFA was reduced in the telmisartan group, while the SFA did not change in either group. CONCLUSION: Telmisartan improves both hemodynamic and metabolic abnormalities found in hypertensive patients with obesity. The additional benefits may be partly due to visceral fat remodeling.