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

A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2

Blood levels of adiponectin, an adipocyte-secreted protein correlated with metabolic and cardiovascular risks, are highly heritable. Genome-wide association (GWA) studies for adiponectin levels have identified 14 loci harboring variants associated with blood levels of adiponectin. To identify novel adiponectin-associated loci, particularly those of importance in East Asians, we conducted a meta-analysis of GWA studies for adiponectin in 7827 individuals, followed by two stages of replications in 4298 and 5954 additional individuals. We identified a novel adiponectin-associated locus on chromosome 10 near WDR11-FGFR2 (P = 3.0 × 10−14) and provided suggestive evidence for a locus on chromosome 12 near OR8S1-LALBA (P = 1.2 × 10−7). Of the adiponectin-associated loci previously described, we confirmed the association at CDH13 (P = 6.8 × 10−165), ADIPOQ (P = 1.8 × 10−22), PEPD (P = 3.6 × 10−12), CMIP (P = 2.1 × 10−10), ZNF664 (P = 2.3 × 10−7) and GPR109A (P = 7.4 × 10−6). Conditional analysis at ADIPOQ revealed a second signal with suggestive evidence of association only after conditioning on the lead SNP (Pinitial = 0.020; Pconditional = 7.0 × 10−7). We further confirmed the independence of two pairs of closely located loci (<2 Mb) on chromosome 16 at CMIP and CDH13, and on chromosome 12 at GPR109A and ZNF664. In addition, the newly identified signal near WDR11-FGFR2 exhibited evidence of association with triglycerides (P = 3.3 × 10−4), high density lipoprotein cholesterol (HDL-C, P = 4.9 × 10−4) and body mass index (BMI)-adjusted waist–hip ratio (P = 9.8 × 10−3). These findings improve our knowledge of the genetic basis of adiponectin variation, demonstrate the shared allelic architecture for adiponectin with lipids and central obesity and motivate further studies of underlying mechanisms

The trans-ancestral genomic architecture of glycemic traits

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 x 10(-8)), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution. A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.Peer reviewe

Effects of Collagen Hydrolysates on Human Brain Structure and Cognitive Function: A Pilot Clinical Study

This study investigated the effects of collagen hydrolysates (CH) on language cognitive function and brain structure. In this open-label study, 5 g CH was administered once a day for 4 weeks to 30 healthy participants aged 49&ndash;63 years. The primary outcome measures were the brain healthcare quotients based on gray matter volume (GM-BHQ) and fractional anisotropy (FA-BHQ). The secondary outcome measures were changes in scores between week 0 and week 4 for word list memory (WLM) and standard verbal paired associate learning (S-PA) tests as well as changes in the physical, mental, and role/social component summary scores of the Short Form-36(SF-36) quality of life instrument. CH ingestion resulted in significant improvements in FA-BHQ (p = 0.0095), a measure of brain structure, as well in scores for the WLM (p = 0.0046) and S-PA (p = 0.0007) tests, which measure cognitive function. There were moderate correlations between the change in WLM score and the change in GM-BHQ (r = 0.4448; Spearman&rsquo;s rank correlation) and between the change in S-PA score and the change in FA-BHQ (r = 0.4645). Daily ingestion of CH changed brain structure and improved language cognitive function

Leptin in sarcopenic visceral obesity: possible link between adipocytes and myocytes.

The combination of sarcopenia, age-related loss of muscle strength and mass, and obesity has been recognized as a new category of obesity among the elderly. Given that leptin has been hypothesized to be involved in the pathogenesis of sarcopenic obesity, we investigated the relationship between plasma leptin levels and thigh muscle sarcopenia and visceral obesity. Thigh muscle cross-sectional area (CSA) and visceral fat area were measured using computed tomography as indices for muscle mass and visceral fat, respectively, in 782 middle-aged to elderly subjects (303 men and 479 women), participating in a medical check-up program. Visceral obesity was defined as visceral fat area >100 cm², and sarcopenia was defined as < (one standard deviation--mean of thigh muscle CSA/body weight of young subjects [aged <50 years]).Thigh muscle CSA was significantly and negatively associated with plasma levels of leptin in both men (β = -0.28, p<0.0001) and women (β = -0.20, p<0.0001), even after correcting for other confounding parameters, including age, body weight, body height, visceral fat area, blood pressure, homeostatic model assessment index, and high sensitive C reactive protein. Subjects were divided into four groups based on presence or absence of sarcopenia or visceral obesity. Plasma levels of leptin were higher in subjects with sarcopenic visceral obesity than in those with either sarcopenia or visceral obesity alone. These findings indicate that sarcopenic visceral obesity is a more advanced, and suggest that leptin may link visceral obesity and sarcopenia