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In epidemiology, the regression discontinuity design has received increasing attention recently and might be an alternative to randomized controlled trials (RCTs) to evaluate treatment effects. In regression discontinuity, treatment is assigned above a certain threshold of an assignment variable for which the treatment effect is adjusted in the analysis. We performed simulations and a validation study in which we used treatment effect estimates from an RCT as the reference for a prospectively performed regression discontinuity study. We estimated the treatment effect using linear regression adjusting for the assignment variable both as linear terms and restricted cubic spline and using local linear regression models. In the first validation study, the estimated treatment effect from a cardiovascular RCT was -4.0 mmHg blood pressure (95% confidence interval: -5.4, -2.6) at 2 years after inclusion. The estimated effect in regression discontinuity was -5.9 mmHg (95% confidence interval: -10.8, -1.0) with restricted cubic spline adjustment. Regression discontinuity showed different, local effects when analyzed with local linear regression. In the second RCT, regression discontinuity treatment effect estimates on total cholesterol level at 3 months after inclusion were similar to RCT estimates, but at least six times less precise. In conclusion, regression discontinuity may provide similar estimates of treatment effects to RCT estimates, but requires the assumption of a global treatment effect over the range of the assignment variable. In addition to a risk of bias due to wrong assumptions, researchers need to weigh better recruitment against the substantial loss in precision when considering a study with regression discontinuity versus RCT design. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined cerebral damage in adults with Tetralogy of Fallot (TOF), a common cyanotic congenital heart disease, using neuropsychological examination and structural magnetic resonance imaging (MRI). The study used univariate logistic regression to evaluate factors related to cerebral damage. Results showed that structural cerebral damage and cognitive impairment are common with adult patients with TOF.

Background and Purpose: Cardiovascular risk factors are associated with an increased risk of dementia. Treatment of hypertension and hypercholesterolemia is associated with a decrease in incident dementia. Whether interventions aimed at cardiovascular risk factors in late life also reduce dementia risk is unknown. Here, we report the outline of a pragmatic study that will attempt to answer this question and we describe the prevalence of cardiovascular risk factors in the target population. Methods: We designed a large cluster-randomized trial with a 6- year follow-up in 3700 elderly subjects (70 to 78 y) to assess whether nurse-led intensive vascular care in primary care decreases the incidence of dementia and reduces disability. Secondary outcome parameters are mortality, incidence of vascular events, and cognitive functioning. Intensive vascular care comprises treatment of hypertension, hypercholesterolemia, diabetes and reducing overweight, smoking cessation, and stimulating physical exercise. Results: Baseline data of 1004 subjects show that 87% of the subjects have I or more cardiovascular risk factors and 44% have even 2 or more risk factors amenable to treatment. Seventy-nine percent of the subjects receiving antihypertensive medication still have a systolic pressure of > 140 mm Hg. Conclusions: In this older age group, the very high percentage of elderly subjects with cardiovascular risk factors illustrates the large window of opportunity for therapies directed to lower the cardiovascular risk and potentially also the risk for dementia. [ABSTRACT FROM AUTHOR]

Objective: High blood pressure is one of the main modifiable risk factors for dementia. However, there is conflicting evidence regarding the best antihypertensive class for optimizing cognition. Our objective was to determine whether any particular antihypertensive class was associated with a reduced risk of cognitive decline or dementia using comprehensive meta-analysis including reanalysis of original participant data., Methods: To identify suitable studies, MEDLINE, Embase, and PsycINFO and preexisting study consortia were searched from inception to December 2017. Authors of prospective longitudinal human studies or trials of antihypertensives were contacted for data sharing and collaboration. Outcome measures were incident dementia or incident cognitive decline (classified using the reliable change index method). Data were separated into mid and late-life (>65 years) and each antihypertensive class was compared to no treatment and to treatment with other antihypertensives. Meta-analysis was used to synthesize data., Results: Over 50,000 participants from 27 studies were included. Among those aged >65 years, with the exception of diuretics, we found no relationship by class with incident cognitive decline or dementia. Diuretic use was suggestive of benefit in some analyses but results were not consistent across follow-up time, comparator group, and outcome. Limited data precluded meaningful analyses in those ≤65 years of age., Conclusion: Our findings, drawn from the current evidence base, support clinical freedom in the selection of antihypertensive regimens to achieve blood pressure goals., Clinical Trials Registration: The review was registered with the international prospective register of systematic reviews (PROSPERO), registration number CRD42016045454., (© 2019 American Academy of Neurology.)

Objective: To assess if HIV-infected patients on long-term successful combination antiretroviral therapy show cerebral blood flow (CBF) alterations in comparison with HIV-uninfected, otherwise similar controls. To explore whether such alterations are associated with HIV-associated cognitive impairment and to explore potential determinants of CBF alterations in HIV., Design: Cross-sectional comparison of CBF in an observational cohort study., Methods: Clinical, cognitive and MRI data of 100 middle-aged aviremic HIV-infected men on combination antiretroviral therapy and 69 HIV-uninfected controls were collected and compared. From pseudocontinuous arterial spin labeling MRI data, CBF-maps were calculated. The associations of mean gray matter CBF with clinical and cognitive parameters were explored in regression models, followed by a spatial delineation in a voxel-based analysis., Results: CBF was decreased in HIV-infected patients compared with HIV-uninfected controls (P = 0.02), adjusted for age, ecstasy use and waist circumference. Spatially distinct and independent effects of total gray matter volume and HIV-serostatus on CBF were found. Within the HIV-infected group, decreased CBF was associated with increased triglyceride levels (P = 0.005) and prior clinical AIDS (P = 0.03). No association between CBF and cognitive impairment was found., Conclusion: Decreased CBF was observed among HIV-infected patients, which was associated with both vascular risk factors as well as with measures of past immune deficiency. These results provide support for increased vascular disease in HIV-infected patients as represented by hemodynamic alteration, but without overt cognitive consequences within the current cohort of patients on long-term successful treatment.

Objectives: The objective of this study was to assess whether HIV-infected patients on long-term successful combination antiretroviral therapy (cART) have more extensive white matter hyperintensities (WMH) of presumed vascular origin compared with uninfected controls and whether these intensities are associated with cognitive impairment. Furthermore, we explored potential determinants of increased WMH load long-term suppressed HIV infection., Design: A cross-sectional comparison of WMH in an observational cohort., Methods: Clinical, cognitive, and MRI data were collected from 103 middle-aged, aviremic HIV-infected men on cART, and 70 HIV-uninfected, otherwise similar controls. In the MRI data, WMH load was quantified by automated approaches and qualitatively reviewed by an experienced neuroradiologist using the Fazekas scale., Results: HIV-infected men had an increased WMH load. Among HIV-infected patients, increased WMH load was independently associated with older age, higher DBP, higher D-dimer levels, and longer time spent with a CD4 cell count below 500 cells/μl. HIV-associated cognitive deficits were associated with increased WMH load., Conclusions: WMH are more extensive and associated with cognitive deficits in middle-aged, aviremic cART-treated HIV-infected men. The extent of WMH load was associated with both cardiovascular risk factors and past immune deficiency. As cognitive impairment in these same patients is also associated with these risk factors, this may suggest that in the setting of HIV, WMH, and cognitive deficits share a common cause. This supports the importance of optimizing cardiovascular risk management, and early, effective treatment of HIV infection.