Ventricular dilation: association with gait and cognition.

Objective: Normal pressure hydrocephalus is characterized by gait impairment, cognitive impairment, and urinary incontinence, and is associated with disproportionate ventricular dilation. Here we report the distribution of ventricular volume relative to sulcal cerebrospinal fluid (CSF) volume, and the association of increasing ventricular volume relative to sulcal CSF volume with a cluster of gait impairment, cognitive impairment, and urinary incontinence in a stroke-free cohort of elderly persons from the general population.

Methods: Data are based on 858 persons (35.

Variants in ZFHX3 are associated with atrial fibrillation in individuals of European ancestry.

We conducted meta-analyses of genome-wide association studies for atrial fibrillation (AF) in participants from five community-based cohorts. Meta-analyses of 896 prevalent (15,768 referents) and 2,517 incident (21,337 referents) AF cases identified a new locus for AF (ZFHX3, rs2106261, risk ratio RR = 1.19; P = 2.

NRXN3 is a novel locus for waist circumference: a genome-wide association study from the CHARGE Consortium.

Central abdominal fat is a strong risk factor for diabetes and cardiovascular disease. To identify common variants influencing central abdominal fat, we conducted a two-stage genome-wide association analysis for waist circumference (WC). In total, three loci reached genome-wide significance.

Migraine headache in middle age and late-life brain infarcts.

Context: Migraine is considered to be an episodic condition with no long-term consequences. However, recent studies suggest that migraine attacks may be associated with pathologic changes in the brain, particularly in the cerebellum.

Objective: To determine whether individuals not reporting headache compared with individuals reporting migraine symptoms, particularly aura, in midlife are at increased risk of late-life infarct-like lesions found on magnetic resonance imaging (MRI) without consideration of clinical symptoms.

Glycemic status and brain injury in older individuals: the age gene/environment susceptibility-Reykjavik study.

Objective: To examine the association of glycemic status to magnetic resonance imaging indicators of brain pathological changes.

Research Design And Methods: This was a cross-sectional, population-based study of 4,415 men and women without dementia (mean age 76 years) participating in the Age Gene/Environment Susceptibility-Reykjavik Study. Glycemic status groups included the following: type 2 diabetes (self-report of diabetes, use of diabetes medications, or fasting blood glucose > or =7.

Microvascular lesions in the brain and retina: The age, gene/environment susceptibility-Reykjavik study.

Objective: To investigate whether the severity and location of cerebral white matter hyperintensities (WMHs) and brain infarcts are correlated with the signs of retinal microvascular abnormalities in the elderly.

Methods: The study included 4,176 men and women (mean age, 76 years) who participated in the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study. Digital retinal images of both dilated eyes were taken and evaluated for the presence of retinal focal arteriolar signs (focal arteriolar narrowing and arteriovenous nicking) and retinopathy lesions (retinal blot hemorrhages and microaneurysms).

Meta-analysis of genome-wide association data identifies two loci influencing age at menarche.

We conducted a meta-analysis of genome-wide association data to detect genes influencing age at menarche in 17,510 women. The strongest signal was at 9q31.2 (P = 1.

Genome-wide association study of blood pressure and hypertension.

Blood pressure is a major cardiovascular disease risk factor. To date, few variants associated with interindividual blood pressure variation have been identified and replicated. Here we report results of a genome-wide association study of systolic (SBP) and diastolic (DBP) blood pressure and hypertension in the CHARGE Consortium (n = 29,136), identifying 13 SNPs for SBP, 20 for DBP and 10 for hypertension at P < 4 × 10(-7).

Unfavourable risk factors for type 2 diabetes mellitus are already apparent more than a decade before onset in a population-based study of older persons: from the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik).

We evaluated midlife risk factors of developing type 2 diabetes mellitus (T2DM) in late life in a population-based study of older persons. A cohort of 2,251 persons, aged 65-96, participated in AGES-Reykjavik in 2002-2004; all attended the Reykjavik Study 26 years earlier, at the mean age of 50. Based on glucometabolic status in 2002-2004 the participants are divided into a normoglycemic control group (n = 1,695), an impaired fasting glucose (IFG) group (n = 313) and T2DM group (n = 243).

The interaction of adiposity with the CRP gene affects CRP levels: age, gene/environment susceptibilty-Reykjavik study.

Objective: Common diseases often have an inflammatory component reflected by associated markers such as serum C-reactive protein (CRP) levels. Circulating CRP levels have also been associated with adipose tissue as well as with specific CRP genotypes. We examined the interaction between measures of body mass index (BMI), waist circumference and fat percent (total fat measured by bioimpedance) with genotypes of the CRP gene in the determination of CRP levels.

Cerebral infarcts and cognitive performance: importance of location and number of infarcts.

Background And Purpose: Cerebral infarcts increase the risk for cognitive impairment. The relevance of location and number of infarcts with respect to cognitive function is less clear.

Methods: We studied the cross-sectional association between number and location of infarcts and cognitive performance in 4030 nondemented participants of the Age Gene/Environment Susceptibility-Reykjavik Study.

Hand osteoarthritis in older women is associated with carotid and coronary atherosclerosis: the AGES Reykjavik study.

Objective: There is evidence that atherosclerosis may contribute to the initiation or progression of osteoarthritis. To test this hypothesis, the presence and severity of hand osteoarthritis (HOA) was compared with markers of atherosclerotic vascular disease in an elderly population.

Patients And Methods: The AGES Reykjavik Study is a population-based multidisciplinary study of ageing in the elderly population of Reykjavik.

High hand joint mobility is associated with radiological CMC1 osteoarthritis: the AGES-Reykjavik study.

Objective: Previous studies have indicated that joint hypermobility may affect the development of clinical and radiological hand osteoarthritis (OA), but this question has not been addressed in epidemiological studies. Our objective was to investigate this relationship in a population-based study.

Patients And Methods: The study group consisted of 384 unselected older participants in the Age, Gene/Environment Susceptibility-Reykjavik Study (161 males, median age 76, range 69-90, and 223 females median age 75, range 69-92).

Cognitive impairment: an increasingly important complication of type 2 diabetes: the age, gene/environment susceptibility--Reykjavik study.

Persons with type 2 diabetes are at increased risk of cognitive dysfunction. Less is known about which cognitive abilities are affected and how undiagnosed diabetes and impaired fasting glucose relate to cognitive performance. The authors explored this question using data from 1,917 nondemented men and women (average age = 76 years) in the population-based Age, Gene/Environment Susceptibility-Reykjavik Study (2002-2006).

Magnetization transfer imaging, white matter hyperintensities, brain atrophy and slower gait in older men and women.

Objective: To assess whether markers of micro- and macrostructural brain abnormalities are associated with slower gait in older men and women independent of each other, and also independent of health-related conditions and of behavioral, cognitive and peripheral function.

Methods: Magnetization transfer ratio [MTR], white matter hyperintensities [WMH], brain atrophy [BA] and brain infarcts [BI] were measured in 795 participants of the AGES-Reykjavik Study cohort (mean 75.6 years, 58.

White matter lesions and cognitive performance: the role of cognitively complex leisure activity.

Background: Among persons with white matter lesions (WMLs), there is a range of cognitive function. We examine whether participation in leisure activities modifies the effect of WML load on cognitive function.

Methods: Data are from 2300 men and women (aged 66-92 years) participating in the population-based Age Gene/Environment Susceptibility-Reykjavik Study.

Localized measures of callosal atrophy are associated with late-life hypertension: AGES-Reykjavik Study.

Hypertension is highly prevalent in elderly individuals and may be associated with cognitive decline, but the mechanisms by which hypertension may impact brain structure, and thereby modulate the time course of late-life cognitive performance, are not well understood. Therefore we used Localized Components Analysis, a novel computational method, to measure spatially-localized patterns of corpus callosum (CC) atrophy in 28 right-handed female subjects aged 75-79 years in the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-Reykjavik), a large-scale epidemiological study of aging. Localized callosal atrophy in the posterior midbody and splenium was significantly associated with systolic blood pressure in linear statistical models that controlled for age, while associations between blood pressure and anterior CC atrophy measures were not statistically significant.

Intra-individual change over time in DNA methylation with familial clustering.

Context: Changes over time in epigenetic marks, which are modifications of DNA such as by DNA methylation, may help explain the late onset of common human diseases. However, changes in methylation or other epigenetic marks over time in a given individual have not yet been investigated.

Objectives: To determine whether there are longitudinal changes in global DNA methylation in individuals and to evaluate whether methylation maintenance demonstrates familial clustering.

Long-term interleukin-6 levels and subsequent risk of coronary heart disease: two new prospective studies and a systematic review.

Background: The relevance to coronary heart disease (CHD) of cytokines that govern inflammatory cascades, such as interleukin-6 (IL-6), may be underestimated because such mediators are short acting and prone to fluctuations. We evaluated associations of long-term circulating IL-6 levels with CHD risk (defined as nonfatal myocardial infarction [MI] or fatal CHD) in two population-based cohorts, involving serial measurements to enable correction for within-person variability. We updated a systematic review to put the new findings in context.

Lipoprotein(a) levels and risk of future coronary heart disease: large-scale prospective data.

Background: Large-scale prospective data are needed to determine whether associations between lipoprotein(a) (Lp[a]) and coronary heart disease (CHD) risk are independent of established risk factors, to characterize the shape of this relationship, and to quantify associations in relevant subgroups.

Methods: Levels of Lp(a) were measured in samples obtained at baseline from 2047 patients who had first-ever nonfatal myocardial infarction or who died of CHD during the study and from 3921 control participants in the Reykjavik Study (n=18 569), as well as in paired samples obtained 12 years apart from 372 participants to quantify within-person fluctuations.

Results: Baseline Lp(a) levels had little or no correlation with known cardiovascular risk factors, such as age, sex, total cholesterol level, and blood pressure.

Genetics of gene expression and its effect on disease.

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity.

Retinal and cerebral microvascular signs and diabetes: the age, gene/environment susceptibility-Reykjavik study.

Objective: Diabetes increases the risk for microvascular disease. The retina and the brain both have intricate microvascular systems that are developmentally similar. We sought to examine whether microvascular lesions in the retina and in the brain are associated and whether this association differs among people with and without diabetes.

Cerebral microbleeds in the population based AGES-Reykjavik study: prevalence and location.

Background And Purpose: Incidental foci of signal loss suggestive of cerebral microbleeds (CMBs) are frequent findings on gradient echo T2* weighted MRI (T2* MRI) of patients with haemorrhagic or ischaemic stroke. There are few prevalence data on older populations. This paper reports on the prevalence and location of CMBs in a community based cohort of older men and women (born 1907-1935) who participated in the Age Gene/Environment Susceptibility (AGES)-Reykjavik Study, a population based cohort study that followed the Reykjavik Study

Methods: As part of the examination, all eligible and consenting cohort members underwent a full brain MRI, and blood was drawn for genotyping.

Renal function and risk of coronary heart disease in general populations: new prospective study and systematic review.

Background: End-stage chronic kidney disease is associated with striking excesses of cardiovascular mortality, but it is uncertain to what extent renal function is related to risk of subsequent coronary heart disease (CHD) in apparently healthy adults. This study aims to quantify the association of markers of renal function with CHD risk in essentially general populations.

Methods And Findings: Estimated glomerular filtration rate (eGFR) was calculated using standard prediction equations based on serum creatinine measurements made in 2,007 patients diagnosed with nonfatal myocardial infarction or coronary death during follow-up and in 3,869 people without CHD in the Reykjavik population-based cohort of 18,569 individuals.

Reliability of quantitative EEG features.

Objective: To investigate the reliability of several well-known quantitative EEG (qEEG) features in the elderly in the resting, eyes closed condition and study the effects of epoch length and channel derivations on reliability.

Methods: Fifteen healthy adults, over 50 years of age, underwent 10 EEG recordings over a 2-month period. Various qEEG features derived from power spectral, coherence, entropy and complexity analysis of the EEG were computed.