The Association between Hypertension and Dementia in the Elderly

Hypertension (HT) and dementia are common disorders in the elderly. HT in the elderly is associated with increased occurrence rates of dementia including Alzheimer's disease (AD) and vascular dementia (VaD). In connection to this, some studies have suggested that HT in old age correlates with the pathogenesis of dementia. Since HT is potentially reversible, a number of randomized trials have examined whether antihypertensive treatment may help in preventing dementia occurrence. We review five studies, all using subjects 60 years or older, which investigated different antihypertensive pharmacological treatments. Data from two trials (Syst-Eur, PROGRESS) open the way toward the prevention of dementia (AD or VaD) by antihypertensive treatments. In the Syst-Eur study, with the dihydropyridine calcium antagonists, a reduction in both types of dementia was demonstrated (risk reduction 55%). The PROGRESS study showed that the use of angiotensin-converting enzyme inhibitors (ACEIs), with or without diuretics, resulted in decrease incidence of stroke-related dementia (risk reduction 19%), but dementia without stroke was not reduced. In contrast, the SHEP trial, treatment with a chlorthalidone-based antihypertensive regimen, did not significantly reduced the incidence of dementia. The SCOPE study (candesartan or hydrochlorothiazide versus placebo) and the HYVET-COG study (indapamide or perindopril versus placebo) found no significant difference between the active treatment and placebo group on the incidence of dementia. We found conflicting results regarding treatment benefits in dementia prevention. Recent clinical trials and studies on animal models suggest that blockades of RAS system could have reduced cognitive decline seen in Alzheimer's disease and vascular dementia. Future trials primarily designed to investigate the effects of antihypertensive agents on impaired cognition are needed

The Association between Hypertension and Dementia

Hypertension (HT) and dementia are common disorders in the elderly. HT in the elderly is associated with increased occurrence rates of dementia including Alzheimer's disease (AD) and vascular dementia (VaD). In connection to this, some studies have suggested that HT in old age correlates with the pathogenesis of dementia. Since HT is potentially reversible, a number of randomized trials have examined whether antihypertensive treatment may help in preventing dementia occurrence. We review five studies, all using subjects 60 years or older, which investigated different antihypertensive pharmacological treatments. Data from two trials (Syst-Eur, PROGRESS) open the way toward the prevention of dementia (AD or VaD) by antihypertensive treatments. In the Syst-Eur study, with the dihydropyridine calcium antagonists, a reduction in both types of dementia was demonstrated (risk reduction 55%). The PROGRESS study showed that the use of angiotensin-converting enzyme inhibitors (ACEIs), with or without diuretics, resulted in decrease incidence of stroke-related dementia (risk reduction 19%), but dementia without stroke was not reduced. In contrast, the SHEP trial, treatment with a chlorthalidone-based antihypertensive regimen, did not significantly reduced the incidence of dementia. The SCOPE study (candesartan or hydrochlorothiazide versus placebo) and the HYVET-COG study (indapamide or perindopril versus placebo) found no significant difference between the active treatment and placebo group on the incidence of dementia. We found conflicting results regarding treatment benefits in dementia prevention. Recent clinical trials and studies on animal models suggest that blockades of RAS system could have reduced cognitive decline seen in Alzheimer's disease and vascular dementia. Future trials primarily designed to investigate the effects of antihypertensive agents on impaired cognition are needed

Efficacy of Zolpidem for Dystonia: A Study Among Different Subtypes

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

Zolpidem therapy in dystonia

Although there are some newly developed options to treat dystonia, its medical treatment is not always satisfactory. Zolpidem, an imidazopyridine agonist with a high affinity on benzodiazepine subtype receptor BZ1 (ω1), was found to improve clinical symptoms of dystonia in a limited number of case reports. To investigate what subtype of dystonia is responsive to the therapy, we conducted an open label study to assess the efficacy of zolpidem (5–20 mg) in 34 patients suffering from miscellaneous types of dystonia using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS). Patients were entered into the study if they had been refractory to other medications as evaluated by BFMDRS (no change in the previous two successive visits). After zolpidem therapy, the scores in the patients as a whole were decreased from 7.2 ± 7.9 to 5.5 ± 5.0 (P = 0.042). Patients with generalized dystonia, Meige syndrome/blepharospasm, and hand dystonia improved in the scale by 27.8, 17.8, and 31.0%, respectively, whereas no improvement was found in cervical dystonia patients. Overall response rate among patients were comparable to that of trihexyphenidyl. Zolpidem may be a therapeutic option for generalized dystonia, Meige syndrome, and hand dystonia including musician’s. Drowsiness was the dose-limiting factor

A structural constraint for functional interaction between N-terminal and C-terminal domains in simian immunodeficiency virus capsid proteins

<p>Abstract</p> <p>Background</p> <p>The Gag capsid (CA) is one of the most conserved proteins in highly-diversified human and simian immunodeficiency viruses (HIV and SIV). Understanding the limitations imposed on amino acid sequences in CA could provide valuable information for vaccine immunogen design or anti-HIV drug development. Here, by comparing two pathogenic SIV strains, SIVmac239 and SIVsmE543-3, we found critical amino acid residues for functional interaction between the N-terminal and the C-terminal domains in CA.</p> <p>Results</p> <p>We first examined the impact of Gag residue 205, aspartate (Gag205D) in SIVmac239 and glutamate (Gag205E) in SIVsmE543-3, on viral replication; due to this difference, Gag_206-216(IINEEAADWDL) epitope-specific cytotoxic T lymphocytes (CTLs) were previously shown to respond to SIVmac239 but not SIVsmE543-3 infection. A mutant SIVmac239, SIVmac239Gag205E, whose Gag205D is replaced with Gag205E showed lower replicative ability. Interestingly, however, SIVmac239Gag205E passaged in macaque T cell culture often resulted in selection of an additional mutation at Gag residue 340, a change from SIVmac239 valine (Gag340V) to SIVsmE543-3 methionine (Gag340M), with recovery of viral fitness. Structural modeling analysis suggested possible intermolecular interaction between the Gag205 residue in the N-terminal domain and Gag340 in the C-terminal in CA hexamers. The Gag205D-to-Gag205E substitution in SIVmac239 resulted in loss of in vitro core stability, which was recovered by additional Gag340V-to-Gag340M substitution. Finally, selection of Gag205E plus Gag340M mutations, but not Gag205E alone was observed in a chronically SIVmac239-infected rhesus macaque eliciting Gag_206-216-specific CTL responses.</p> <p>Conclusions</p> <p>These results present in vitro and in vivo evidence implicating the interaction between Gag residues 205 in CA NTD and 340 in CA CTD in SIV replication. Thus, this study indicates a structural constraint for functional interaction between SIV CA NTD and CTD, providing insight into immunogen design to limit viral escape options.</p

High-sensitivity c-reactive protein and gamma-glutamyl transferase levels are synergistically associated with metabolic syndrome in community-dwelling persons

<p>Abstract</p> <p>Background</p> <p>Metabolic syndrome (MetS) is associated with an increased risk of major cardiovascular events. Increased high-sensitivity C-reactive protein (hsCRP) levels are associated with MetS and its components. Changes in gamma-glutamyl transferase (GGT) levels in response to oxidative stress are also associated with MetS, and the levels could be modulated by hsCRP.</p> <p>Methods</p> <p>From a single community, we recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination. We investigated whether increased hsCRP and GGT levels are synergistically associated with MetS and insulin resistance evaluated by Homeostasis of model assessment of insulin resistance (HOMA-IR).</p> <p>Results</p> <p>Of these subjects, 141 men (17.2%) and 170 women (15.5%) had MetS. Participants with MetS had a higher hsCRP and GGT level than those without MetS in both genders, and the HOMA-IR increased significantly in correlation with an increase in hsCRP and GGT. In men, the adjusted odds ratios (95% confidence interval) for MetS across tertiles of hsCRP and GGT were 1.00, 1.69 (1.01-2.80), and 2.13 (1.29-3.52), and 1.00, 3.26 (1.84-5.78) and 6.11 (3.30-11.3), respectively. In women, the respective corresponding values were 1.00, 1.54 (0.92-2.60), and 3.08 (1.88-5.06), and 1.00, 1.70 (1.04-2.79) and 2.67 (1.66-4.30). The interaction between increased hsCRP and GGT was a significant and independent determinant for MetS and insulin resistance in both genders.</p> <p>Conclusions</p> <p>These results suggested that higher CRP and GGT levels were synergistically associated with MetS and insulin resistance, independently of other confounding factor in the general population.</p

Association between fasting plasma glucose and high-sensitivity C-reactive protein: gender differences in a Japanese community-dwelling population

<p>Abstract</p> <p>Background</p> <p>High sensitivity C-reactive protein (hsCRP) is an acute phase reactant and a sensitive marker of inflammation. Hyperglycemia can potentially promote the production of CRP. The aim of this study was to determine whether increased fasting plasma glucose (FPG) levels are associated with elevated hsCRP concentrations by gender.</p> <p>Methods</p> <p>We recruited 822 men (mean age, 61 ± 14 years) and 1,097 women (63 ± 12 years) during their annual health examination from a single community. We cross-sectionally examined whether FPG levels are associated with hsCRP concentrations, and whether this association is independent of gender, body mass index (BMI) and other components of the metabolic syndrome.</p> <p>Results</p> <p>In women only, hsCRP increased significantly and progressively with increasing FPG (r = 0.169, P < 0.001). The stepwise multiple linear regression analysis using hsCRP as an objective variable, adjusted for confounding factors as explanatory variables, showed that FPG as well as age, BMI, systolic blood pressure, high-density lipoprotein cholesterol (HDL-C), uric acid, and high molecular weight adiponectin were significantly associated with hsCRP in women, but not in men. There was significant gender interaction, and an increase in hsCRP levels that was greater in women with BMI ≥ 25 kg/m²and higher FPG than in men.</p> <p>Conclusions</p> <p>These results suggested that hsCRP levels increase continuously across the FPG spectrum starting from the lowest FPG in both men and women. However, increase in hsCRP levels was greater in women than men.</p

Low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio is the best surrogate marker for insulin resistance in non-obese Japanese adults

<p>Abstract</p> <p>Background</p> <p>The aim of the present study was to examine how lipid profiles are associated with insulin resistance in Japanese community-dwelling adults.</p> <p>Methods</p> <p>This cross-sectional study included 614 men aged 58 ± 14 (mean ± standard deviation; range, 20-89) years and 779 women aged 60 ± 12 (range, 21-88) years. The study sample were 1,042 (74.8%) non-obese (BMI < 25.0 kg/m²) and 351 (25.2%) overweight (BMI ≥ 25 kg/m²) subjects. Insulin resistance was defined by homeostasis model assessment of insulin resistance (HOMA-IR) of at least 2.5. The areas under the curve (AUC) of the receiver operating characteristic curves (ROC) were used to compare the power of these serum markers.</p> <p>Results</p> <p>In non-obese subjects, the best marker of insulin resistance was low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C) ratio of 0.74 (95% confidence interval (CI), 0.66-0.80). The HDL-C, triglyceride (TG)/HDL-C ratio, and non-HDL-C also discriminated insulin resistance, as the values for AUC were 0.31 (95% CI, 0.24-0.38), 0.69 (95% CI, 0.62-0.75) and 0.69 (95% CI, 0.62-0.75), respectively. In overweight subjects, the AUC for TG and TG/HDL-C ratio were 0.64 (0.58-0.71) and 0.64 (0.57-0.70), respectively. The optimal cut-off point to identifying insulin resistance for these markers yielded the following values: TG/HDL-C ratio of ≥1.50 and LDL-C/HDL-C ratio of ≥2.14 in non-obese subjects, and ≥2.20, ≥2.25 in overweight subjects. In non-obese subjects, the positive likelihood ratio was greatest for LDL-C/HDL-C ratio.</p> <p>Conclusion</p> <p>In non-obese Japanese adults, LDL-C/HDL-C ratio may be the best reliable marker of insulin resistance.</p