Validation of the CogDrisk Instrument as Predictive of Dementia in Four General Community-Dwelling Populations

Background: Lack of external validation of dementia risk tools is a major limitation for generalizability and translatability of prediction scores in clinical practice and research. Objectives: We aimed to validate a new dementia prediction risk tool called CogDrisk and a version, CogDrisk-AD for predicting Alzheimer’s disease (AD) using cohort studies. Design, Setting, Participants and Measurements: Four cohort studies were identified that included majority of the dementia risk factors from the CogDrisk tool. Participants who were free of dementia at baseline were included. The predictors were component variables in the CogDrisk tool that include self-reported demographics, medical risk factors and lifestyle habits. Risk scores for Any Dementia and AD were computed and Area Under the Curve (AUC) was assessed. To examine modifiable risk factors for dementia, the CogDrisk tool was tested by excluding age and sex estimates from the model. Results: The performance of the tool varied between studies. The overall AUC and 95% CI for predicting dementia was 0.77 (0.57, 0.97) for the Swedish National study on Aging and Care in Kungsholmen, 0.76 (0.70, 0.83) for the Health and Retirement Study - Aging, Demographics and Memory Study, 0.70 (0.67,0.72) for the Cardiovascular Health Study Cognition Study, and 0.66 (0.62,0.70) for the Rush Memory and Aging Project. Conclusions: The CogDrisk and CogDrisk-AD performed well in the four studies. Overall, this tool can be used to assess individualized risk factors of dementia and AD in various population settings

Association of physical function with predialysis blood pressure in patients on hemodialysis

BACKGROUND: New information from various clinical settings suggests that tight blood pressure control may not reduce mortality and may be associated with more side effects. METHODS: We performed cross-sectional multivariable ordered logistic regression to examine the association between predialysis blood pressure and the short physical performance battery (SPPB) in a cohort of 749 prevalent hemodialysis patients in the San Francisco and Atlanta areas recruited from July 2009 to August 2011 to study the relationship between systolic blood pressure and objective measures of physical function. Mean blood pressure for three hemodialysis sessions was analyzed in the following categories: <110 mmHg, 110-129 mmHg (reference), 130-159 mmHg, and ≥160 mmHg. SPPB includes three components: timed repeated chair stands, timed 15-ft walk, and balance tests. SPPB was categorized into ordinal groups (≤6, 7-9, 10-12) based on prior literature. RESULTS: Patients with blood pressure 130-159 mmHg had lower odds (OR 0.57, 95% CI 0.35-0.93) of scoring in a lower SPPB category than those whose blood pressure was between 110 and 129 mmHg, while those with blood pressure ≥160 mmHg had 0.56 times odds (95% CI 0.33-0.94) of scoring in a lower category when compared with blood pressure 110-129 mmHg. When individual components were examined, blood pressure was significantly associated with chair stand (130-159 mmHg: OR 0.59, 95% CI 0.38-0.92) and gait speed (≥160 mmHg: OR 0.59, 95% CI 0.35-0.98). Blood pressure ≥160 mmHg was not associated with substantially higher SPPB score compared with 130-159 mmHg. CONCLUSIONS: Patients with systolic blood pressure at or above 130 mmHg had better physical performance than patients with lower blood pressure in the normotensive range. The risk-benefit tradeoff of aggressive blood pressure control, particularly in low-functioning patients, should be reexamined

Blood Pressure Lowering and Risk of Mortality in Chronic Kidney Disease: A Meta2 Analysis of Randomized Controlled Trials

Importance: Trials in hypertensive patients demonstrate that intensive blood pressure (BP) lowering reduces risk of cardiovascular disease (CVD) and all-cause mortality, but may increase risk of chronic kidney disease (CKD) incidence and progression. Whether intensive BP lowering is associated with a mortality benefit in patients with prevalent CKD remains unknown. Objective: We conducted a meta-analysis of Randomized controlled trials (RCTs) to determine if more intensive, compared with a less intensive, BP control is associated with reduced mortality risk in persons with CKD stages 3-5. Data Sources: Ovid Medline, Cochrane Library, Embase, Pubmed, Science Citation Index, Google Scholar, and ClinicalTrials.gov electronic databases. Study Selection: All RCTs that compared two defined BP targets (either active treatment vs.placebo or no treatment, or intensive vs. less intensive BP control) and enrolled adult (≥18years) persons with CKD stages 3-5 (estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2) exclusively or that included a CKD subgroup between January 1950 and June 2016 were included. Data extraction and synthesis: Two reviewers independently evaluated study quality and extracted characteristics and mortality events among persons with CKD within the intervention phase for each trial. When outcomes within the CKD group had not previously been published, we contacted trial investigators and requested data within the CKD subset of their original trials. Main outcomes and measures: All-cause mortality during the active treatment phase of each trial. Results: We identified 30 RCTs that potentially met inclusion criteria, among which we were able to extract the CKD subset mortality data in 18 trials. Among these, there were 1293 deaths among 15,924 participants with CKD. The mean baseline systolic blood pressure (SBP) was 148±16 mm hg in both intensive and less-intensive arms. The mean SBP dropped by 16 mm Hg to 132 mm Hg in the intensive arm and by 8 mm Hg to 140 mm Hg in the less-intensive arm. More vs. less-intensive BP control resulted in 14% lower risk of all-cause mortality (Odds Ratio (OR) 0.86; 95% CI 0.76 to 0.97, p = 0.01); a finding that was without significant heterogeneity and appeared consistent across multiple subgroups including type of treatment in the comparator arm (placebo vs. less intensive BP target), length of follow-up, presence of diabetes, CKD severity, baseline systolic blood pressure (SBP), achieved SBP during the trial and degree of SBP differences across the treatment arms. Conclusion and Relevance: Randomization to more intensive BP control is associated with lower mortality risk among trial participants with hypertension and CKD. Further studies are required to define absolute BP targets for maximal benefit and minimal harm

A polymorphism near IGF1 is associated with body composition and muscle function in women from the Health, Aging, and Body Composition Study

Previous studies have reported associations of polymorphisms in the IGF1 gene with phenotypes of body composition (BC). The purpose of this study was to identify phenotypes of BC and physical function that were associated with the IGF1 promoter polymorphism (rs35767, −C1245T). Subjects from the Health, Aging, and Body Composition Study, white males and females (n = 925/836) and black males and females (533/705) aged 70–79 years were genotyped for the polymorphism. Phenotypes of muscle size and function, bone mineral density, and BC were analyzed for associations with this polymorphism. To validate and compare these findings, a cohort of young (mean age = 24.6, SD = 5.9) white men and women (n = 173/296) with similar phenotypic measurements were genotyped. An association with BC was identified in elderly females when significant covariates (physical activity, age, smoking status, body mass index) were included. White women with C/C genotype had 3% more trunk fat and 2% more total fat than those with C/T (P < 0.05). Black women with C/C genotype had 3% less total lean mass and 3% less muscle mass than their T/T counterparts (P < 0.05). Associations were identified with muscle strength in white women (P < 0.01) that were in agreement with the C/C genotype having lower muscle function. Thus, in an elderly population but not a young population, a polymorphism in the IGF1 gene may be predictive of differences in body composition, primarily in black females

Relationship of Circulating Soluble Urokinase Plasminogen Activator Receptor (suPAR) Levels to Disease Control in Asthma and Asthmatic Pregnancy

Asthma has a high burden of morbidity if not controlled and may frequently complicate pregnancy, posing a risk for pregnancy outcomes. Elevated plasma level of the inflammatory biomarker soluble urokinase plasminogen activator receptor (suPAR) is related to a worse prognosis in many conditions such as infectious, autoimmune, or pregnancy-related diseases; however the value of suPAR in asthma and asthmatic pregnancy is unknown. The present study aimed to investigate the suPAR, CRP and IL-6 levels in asthma (asthmatic non-pregnant, ANP; N = 38; female N = 27) and asthmatic pregnancy (AP; N = 15), compared to healthy non-pregnant controls (HNP; N = 29; female N = 19) and to healthy pregnant women (HP; N = 58). The relationship between suPAR levels and asthma control was also evaluated. The diagnostic efficacy of suPAR in asthma control was analyzed using ROC analysis. IL-6 and CRP levels were comparable in all study groups. Circulating suPAR levels were lower in HP and AP than in HNP and ANP subjects, respectively (2.01 [1.81-2.38] and 2.39 [2.07-2.69] vs. 2.60 [1.82-3.49] and 2.84 [2.33-3.72] ng/mL, respectively, p = 0.0001). suPAR and airway resistance correlated in ANP (r = 0.47, p = 0.004). ROC analysis of suPAR values in ANP patients with PEF above and below 80% yielded an AUC of 0.75 (95% CI: 0.57-0.92, p = 0.023) and with ACT total score above and below 20 an AUC of 0.80 (95% CI: 0.64-0.95, p = 0.006). The cut-off value of suPAR to discriminate between controlled and not controlled AP and ANP was 4.04 ng/mL. In conclusion, suPAR may help the objective assessment of asthma control, since it correlates with airway resistance and has good sensitivity in the detection of impaired asthma control. Decrease in circulating suPAR levels detected both in healthy and asthmatic pregnant women presumably represents pregnancy induced immune tolerance