Citations

Abstract Introduction The interplay between midlife vascular risk factors and midlife cognitive function with later life mild cognitive impairment (MCI) and dementia (DEM) is not well understood. Methods In the Atherosclerosis Risk in Communities Study, cardiovascular risk factors and cognition were assessed in midlife, ages 45–64 years. In 2011–2013, 20–25 years later, all consenting Atherosclerosis Risk in Communities participants underwent a cognitive and neurological evaluation and were given adjudicated diagnoses of cognitively normal, MCI, or DEM. Results In 5995 participants with complete covariate data, midlife diabetes, hypertension, obesity, and hypercholesterolemia were associated with late‐life MCI and DEM. Low midlife cognition function was also associated with greater likelihood of late‐life MCI or DEM. Both midlife vascular risk factors and midlife cognitive function remained associated with later life MCI or DEM when both were in the model. Discussion Later life MCI and DEM were independently associated with midlife vascular risk factors and midlife cognition.

Background Intracranial aneurysms ( IAs ), abdominal aortic aneurysms ( AAAs ), and thoracic aortic aneurysms ( TAAs ) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs , AAAs, and TAAs . Methods and Results We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study ( GWAS ) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA , AAA , and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA ‐, AAA ‐, and TAA ‐associated SNP s and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls ( IA ) and 4391 cases and 37 904 controls ( AAA ), and found nominally significant associations for IA risk locus 18q11 near RBBP 8 to AAA (odds ratio [ OR ]=1.11; P =4.1×10 −5 ) and for TAA risk locus 15q21 near FBN 1 to AAA ( OR =1.07; P =1.1×10 −3 ). Conclusions Although there was no evidence for polygenic overlap between IAs , AAAs , and TAAs , we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs . These two loci will require further replication.

ABSTRACT Introduction Sexual health is an integral part of overall health. Sexual dysfunction can have a major impact on quality of life and psychosocial and emotional well-being. Aim To provide evidence-based, expert-opinion consensus guidelines for clinical management of sexual dysfunction in men. Methods An international consultation collaborating with major urologic and sexual medicine societies convened in Paris, July 2009. More than 190 multidisciplinary experts from 33 countries were assembled into 25 consultation committees. Committee members established scope and objectives for each chapter. Following an exhaustive review of available data and publications, committees developed evidence-based guidelines in each area. Main Outcome Measures New algorithms and guidelines for assessment and treatment of sexual dysfunctions were developed based on work of previous consultations and evidence from scientific literature published from 2003 to 2009. The Oxford system of evidence-based review was systematically applied. Expert opinion was based on systematic grading of medical literature, and cultural and ethical considerations. Results Algorithms, recommendations, and guidelines for sexual dysfunction in men are presented. These guidelines were developed in an evidence-based, patient-centered, multidisciplinary manner. It was felt that all sexual dysfunctions should be evaluated and managed following a uniform strategy, thus the International Consultation of Sexual Medicine (ICSM-5) developed a stepwise diagnostic and treatment algorithm for sexual dysfunction. The main goal of ICSM-5 is to unmask the underlying etiology and/or indicate appropriate treatment options according to men’s and women’s individual needs (patient-centered medicine) using the best available data from population-based research (evidence-based medicine). Specific evaluation, treatment guidelines, and algorithms were developed for every sexual dysfunction in men, including erectile dysfunction; disorders of libido, orgasm, and ejaculation; Peyronie’s disease; and priapism. Conclusions Sexual dysfunction in men represents a group of common medical conditions that need to be managed from a multidisciplinary perspective.

AbstractGenome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.

BackgroundStrokes, vascular risk factors, and apolipoprotein E (APOE) genotype are associated with cognitive decline in the elderly, but definitive evidence that these affect cognition as early as middle age is limited.ObjectiveWe describe the relationships of APOE genotype, stroke, and vascular risk factors with cognitive change over a 14‐year follow‐up in the Atherosclerosis Risk in Communities (ARIC) Study cohort recruited while in middle age.MethodsParticipants included a subset of the ARIC Study who underwent assessments of cognitive function and vascular risk factors. Four cognitive assessments were performed between 1990–1992 and 2004–2006. Cognitive assessments included the Delayed Word Recall (DWR) Test, the Digit Symbol Substitution (DSS) Test, and the Word Fluency (WF) Test. Vascular risk factors were assessed during the baseline visit in 1990–1992. Incident stroke was recorded over the 14 years of follow‐up.ResultsThere were 1130 participants (mean age, 59 ± 4.3 [SD] years; 62% women; 52% African‐American) with longitudinal data. In multivariate, random‐effects linear models adjusted for age, education, gender, and race, the risk factors diabetes and APOE ɛ4 genotype were independently associated with a decline in performance on the DSS test (both P < .005), whereas hypertension and stroke were not. For DWR, stroke and APOE ɛ4 genotype were independent predictors of decline (both P < .001). For the WF test, metabolic syndrome, hypertension, and stroke were independently associated with decline (all P < .005). No evidence of differential effects of risk factors on cognitive decline by race, gender, or interactions between risk factors was found.ConclusionsThe vascular risk factors diabetes and hypertension, a history of stroke itself, and APOE ɛ4 genotype independently contribute to cognitive decline in late middle age and early elderly years.