PMCC PMCC

Search tips
Search criteria

Advanced
Results 1-25 (72)
 

Clipboard (0)
None

Select a Filter Below

Journals
more »
Year of Publication
more »
1.  Dietary Fats, Cholesterol and Iron as Risk Factors for Parkinson's Disease 
Background
Epidemiologic findings suggest that dietary components may contribute to the etiology of Parkinson's disease (PD). This population-based case-control study evaluated PD risk and dietary intake of fats, cholesterol and iron.
Methods
Newly diagnosed case (n = 420) and age/gender/ethnicity-matched unrelated controls (n = 560) were identified between 1992 and 2006 from the Group Health Cooperative health maintenance organization in western Washington State, and the University of Washington neurology clinic. In-person interviews elicited data on food frequency habits during most of adult life. Nutritional intakes were calculated and analyzed, with adjustments made for total energy intake (the ‘nutrition density’ technique).
Results
Cholesterol intake in the highest quartile compared with the lowest quartile was associated with a decreased risk of PD in men (odds ratio (OR)=0.53, 95% CI: 0.33, 0.86). The highest versus the lowest quartile of dietary iron increased PD risk in men (OR=1.82, 95% CI: 1.11, 2.99). When the lowest quartile of cholesterol and the highest quartile for iron were compared to the highest quartile of cholesterol and the lowest quartile of iron, no association was seen in women, but for men PD risk was increased (OR=2.70, 95% CI: 1.26, 5.76). Saturated fat intake below the median in combination with iron intake above the median also increased PD risk (OR=1.50, 95% CI: 1.07, 2.11) in both genders combined.
Conclusions
A low intake of cholesterol, particularly in the presence of high iron, may be associated with an increased risk for PD.
doi:10.1016/j.parkreldis.2008.03.002
PMCID: PMC2751763  PMID: 18424169
2.  Gene Variants Associated With Ischemic Stroke 
Background and Purpose
The purpose of this study was to determine whether 74 single nucleotide polymorphisms (SNPs), which had been associated with coronary heart disease, are associated with incident ischemic stroke.
Methods
Based on antecedent studies of coronary heart disease, we prespecified the risk allele for each of the 74 SNPs. We used Cox proportional hazards models that adjusted for traditional risk factors to estimate the associations of these SNPs with incident ischemic stroke during 14 years of follow-up in a population-based study of older adults: the Cardiovascular Health Study (CHS).
Results
In white CHS participants, the prespecified risk alleles of 7 of the 74 SNPs (in HPS1, ITGAE, ABCG2, MYH15, FSTL4, CALM1, and BAT2) were nominally associated with increased risk of stroke (one-sided P<0.05, false discovery rate=0.42). In black participants, the prespecified risk alleles of 5 SNPs (in KRT4, LY6G5B, EDG1, DMXL2, and ABCG2) were nominally associated with stroke (one-sided P<0.05, false discovery rate=0.55). The Val12Met SNP in ABCG2 was associated with stroke in both white (hazard ratio, 1.46; 90% CI, 1.05 to 2.03) and black (hazard ratio, 3.59; 90% CI, 1.11 to 11.6) participants of CHS. Kaplan-Meier estimates of the 10-year cumulative incidence of stroke were greater among Val allele homozygotes than among Met allele carriers in both white (10% versus 6%) and black (12% versus 3%) participants of CHS.
Conclusions
The Val12Met SNP in ABCG2 (encoding a transporter of sterols and xenobiotics) was associated with incident ischemic stroke in white and black participants of CHS.
doi:10.1161/STROKEAHA.108.521328
PMCID: PMC2881155  PMID: 19023099
brain infarction; cerebrovascular accident; epidemiology; genetics; prevention; risk factors
3.  Parkinson's disease and history of outdoor occupation 
Parkinsonism & related disorders  2013;19(12):1164-1166.
Background
Human and animal studies, albeit not fully consistent, suggest that vitamin D may reduce risk of Parkinson's disease (PD). Ultraviolet radiation converts vitamin D precursor to the active form. This study examined the hypothesis that working outdoors is associated with a decreased risk of PD.
Methods
PD cases were enrolled from Group Health Cooperative, a health maintenance organization in the Puget Sound region in western Washington State, and the University of Washington Neurology Clinic in Seattle. Participants included 447 non-Hispanic Caucasian newly diagnosed PD cases diagnosed between 1992 and 2008 and 578 unrelated neurologically normal controls enrolled in Group Health Cooperative, frequency matched by race/ethnicity, age and gender. Subjects' amount of outdoor work was estimated from self-reported occupational histories. Jobs were categorized by degree of time spent working outdoors. A ten-year lag interval was included to account for disease latency. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression, with adjustment for age, gender, and smoking.
Results
Outdoor work was inversely associated with risk of PD (outdoor only compared to indoor only): OR= 0.74, 95% CI 0.44-1.25. However, there was no trend in relation to portion of the workday spent laboring outdoors and PD risk.
Conclusion
Occupational sunlight exposure and other correlates of outdoor work is not likely to have a substantial role in the etiology of PD.
doi:10.1016/j.parkreldis.2013.08.014
PMCID: PMC3927788  PMID: 24044947
Parkinson's disease; occupation; ultraviolet radiation; vitamin D
4.  LINE-1 DNA Methylation, Smoking and Risk of Parkinson’s Disease 
Journal of Parkinson's disease  2012;2(4):303-308.
Long interspersed nucleotide element-1 (LINE-1) retrotransposons are located throughout the human genome. Those retaining an intact 5′ promoter can copy and insert themselves into the DNA of neural progenitor cells that express tyrosine hydroxylase, which may influence differentiation and survival of these cells. Because LINE-1 promoter methylation is associated with decreased LINE-1 propagation, we compared LINE-1 methylation profiles in blood mononuclear cells between 292 newly diagnosed Parkinson’s disease (PD) cases and 401 unrelated, neurologically normal controls. Overall, PD was not associated with percent methylation of the LINE-1 promoter. However, the predictable inverse association between PD and ever smoking tobacco was strongest for men and women with the lowest LINE-1 promoter methylation, and less apparent as LINE-1 methylation increased. Underlying this possible interaction, ever regularly smoking tobacco was associated with decreased LINE-1 methylation in controls (age- and sex-adjusted linear regression β = −0.24, 95% confidence interval [CI] −0.43, −0.04), but not in cases (β = 0.06, 95% CI −0.17, 0.28, interaction p = 0.06). PD cases may have innate differences in their ability to respond to tobacco smoke.
doi:10.3233/JPD-012129
PMCID: PMC3962286  PMID: 23938260
5.  Occupational Factors and Risk of Parkinson’s Disease: A Population-Based Case–Control Study 
Background
Parkinson’s disease (PD) has been associated with various workplace factors, but the evidence is inconsistent.
Objective
To estimate the risk of PD associated with various jobs and workplace exposures.
Methods
We conducted a population-based, case–control study of 404 incident PD cases and 526 age and sex-matched controls, collecting self-reported work histories including job titles and exposures to various industrial toxicants. Relative risks of PD from these exposures were estimated with odds ratios (OR) and 95% confidence intervals (CI) using logistic regression.
Results
Risk was not significantly affected by farming work, by metal work, or by exposure to pesticides, metals, or solvents.
Conclusions
These findings do not provide support for the hypothesis that workplace factors affect the risk of PD.
doi:10.1002/ajim.20788
PMCID: PMC3299410  PMID: 20025075
risk factors in epidemiology; Parkinson’s disease/parkinsonism; toxicology; occupational; human
6.  Albuminuria and the risk of incident stroke and stroke types in older adults(e–Pub ahead of print) 
Neurology  2010;75(15):1343-1350.
Background:
The kidney biomarker that best reflects risk of stroke is unknown. We sought to evaluate the association of stroke with 3 kidney biomarkers: albuminuria, cystatin C, and glomerular filtration rate.
Methods:
These 3 biomarkers were determined in 3,287 participants without history of stroke from the Cardiovascular Health Study, a longitudinal cohort study of men and women age 65 years and older from 4 US communities. The biomarkers were albuminuria ascertained using urinary albumin-to-creatinine ratio (UACR) from morning spot urine, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C. Outcomes were incident stroke (any, ischemic, or hemorrhagic) during follow-up between 1996 and 2006.
Results:
A total of 390 participants had an incident stroke: 81% ischemic, 12% hemorrhagic, and 7% unclassified. In adjusted Cox regression models, UACR was more strongly related to any stroke, ischemic stroke, and hemorrhagic stroke than eGFR and cystatin C. The hazard ratio (HR) of any stroke comparing the top to bottom quintile of UACR was 2.10 (95% confidence interval [CI] 1.47-3.00), while HR for eGFR was 1.29 (95% CI 0.91-1.84) and for cystatin C was 1.22 (95% CI 0.85-1.74). When considering clinically relevant categories, elevated UACR was associated with increased hazard of any stroke and ischemic stroke regardless of eGFR or cystatin C categories.
Conclusions:
UACR was the kidney biomarker most strongly associated with risk of incident stroke. Results in this elderly cohort may not be applicable to younger populations. These findings suggest that measures of glomerular filtration and permeability have differential effects on stroke risk.
GLOSSARY
= atrial fibrillation;
= Cardiovascular Health Study;
= confidence interval;
= estimated glomerular filtration rate;
= hazard ratio;
= left ventricular hypertrophy;
= urinary albumin-to-creatinine ratio.
doi:10.1212/WNL.0b013e3181f73638
PMCID: PMC3013484  PMID: 20810996
7.  Genome-wide Studies of Verbal Declarative Memory in Nondemented Older People: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium 
Debette, Stéphanie | Ibrahim Verbaas, Carla A. | Bressler, Jan | Schuur, Maaike | Smith, Albert | Bis, Joshua C. | Davies, Gail | Wolf, Christiane | Gudnason, Vilmundur | Chibnik, Lori B. | Yang, Qiong | deStefano, Anita L. | de Quervain, Dominique J.F. | Srikanth, Velandai | Lahti, Jari | Grabe, Hans J. | Smith, Jennifer A. | Priebe, Lutz | Yu, Lei | Karbalai, Nazanin | Hayward, Caroline | Wilson, James F. | Campbell, Harry | Petrovic, Katja | Fornage, Myriam | Chauhan, Ganesh | Yeo, Robin | Boxall, Ruth | Becker, James | Stegle, Oliver | Mather, Karen A. | Chouraki, Vincent | Sun, Qi | Rose, Lynda M. | Resnick, Susan | Oldmeadow, Christopher | Kirin, Mirna | Wright, Alan F. | Jonsdottir, Maria K. | Au, Rhoda | Becker, Albert | Amin, Najaf | Nalls, Mike A. | Turner, Stephen T. | Kardia, Sharon L.R. | Oostra, Ben | Windham, Gwen | Coker, Laura H. | Zhao, Wei | Knopman, David S. | Heiss, Gerardo | Griswold, Michael E. | Gottesman, Rebecca F. | Vitart, Veronique | Hastie, Nicholas D. | Zgaga, Lina | Rudan, Igor | Polasek, Ozren | Holliday, Elizabeth G. | Schofield, Peter | Choi, Seung Hoan | Tanaka, Toshiko | An, Yang | Perry, Rodney T. | Kennedy, Richard E. | Sale, Michèle M. | Wang, Jing | Wadley, Virginia G. | Liewald, David C. | Ridker, Paul M. | Gow, Alan J. | Pattie, Alison | Starr, John M. | Porteous, David | Liu, Xuan | Thomson, Russell | Armstrong, Nicola J. | Eiriksdottir, Gudny | Assareh, Arezoo A. | Kochan, Nicole A. | Widen, Elisabeth | Palotie, Aarno | Hsieh, Yi-Chen | Eriksson, Johan G. | Vogler, Christian | van Swieten, John C. | Shulman, Joshua M. | Beiser, Alexa | Rotter, Jerome | Schmidt, Carsten O. | Hoffmann, Wolfgang | Nöthen, Markus M. | Ferrucci, Luigi | Attia, John | Uitterlinden, Andre G. | Amouyel, Philippe | Dartigues, Jean-François | Amieva, Hélène | Räikkönen, Katri | Garcia, Melissa | Wolf, Philip A. | Hofman, Albert | Longstreth, W.T. | Psaty, Bruce M. | Boerwinkle, Eric | DeJager, Philip L. | Sachdev, Perminder S. | Schmidt, Reinhold | Breteler, Monique M.B. | Teumer, Alexander | Lopez, Oscar L. | Cichon, Sven | Chasman, Daniel I. | Grodstein, Francine | Müller-Myhsok, Bertram | Tzourio, Christophe | Papassotiropoulos, Andreas | Bennett, David A. | Ikram, Arfan M. | Deary, Ian J. | van Duijn, Cornelia M. | Launer, Lenore | Fitzpatrick, Annette L. | Seshadri, Sudha | Mosley, Thomas H.
Biological psychiatry  2014;77(8):749-763.
BACKGROUND
Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting.
METHODS
We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia-and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10−6) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults.
RESULTS
rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10−10) and replication cohorts (p = 5.65 × 10−8). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10−8, and rs6813517 [SPOCK3], p = 2.58 × 10−8) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism.
CONCLUSIONS
This largest study to date exploring the genetics of memory function in ~ 40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways.
doi:10.1016/j.biopsych.2014.08.027
PMCID: PMC4513651  PMID: 25648963
Alzheimer disease; Dementia; Epidemiology; Genetics; Population-based; Verbal declarative memory
8.  Genome-Wide Association Study of L-Arginine and Dimethylarginines Reveals Novel Metabolic Pathway for Symmetric Dimethylarginine 
Background
Dimethylarginines (DMA) interfere with nitric oxide (NO) formation by inhibiting NO synthase (asymmetric dimethylarginine, ADMA) and L-arginine uptake into the cell (ADMA and symmetric dimethylarginine, SDMA). In prospective clinical studies ADMA has been characterized as a cardiovascular risk marker whereas SDMA is a novel marker for renal function and associated with all-cause mortality after ischemic stroke. The aim of the current study was to characterise the environmental and genetic contributions to inter-individual variability of these biomarkers.
Methods and Results
This study comprised a genome-wide association analysis of 3 well-characterized population-based cohorts (FHS (n=2992), GHS (n=4354) and MONICA/KORA F3 (n=581)) and identified replicated loci (DDAH1, MED23, Arg1 and AGXT2) associated with the inter-individual variability in ADMA, L-arginine and SDMA. Experimental in-silico and in-vitro studies confirmed functional significance of the identified AGXT2 variants. Clinical outcome analysis in 384 patients of the Leeds stroke study demonstrated an association between increased plasma levels of SDMA, AGXT2 variants and various cardiometabolic risk factors. AGXT2 variants were not associated with post-stroke survival in the Leeds study, nor were they associated with incident stroke in the CHARGE consortium.
Conclusion
These GWAS support the importance of DDAH1 and MED23/Arg1 in regulating ADMA and L-arginine metabolism, respectively, and identify a novel regulatory renal pathway for SDMA by AGXT2. AGXT2 variants might explain part of the pathogenic link between SDMA, renal function, and outcome. An association between AGXT2 variants and stroke is unclear and warrants further investigation.
doi:10.1161/CIRCGENETICS.113.000264
PMCID: PMC4797637  PMID: 25245031
biomarker; endothelial function; nitric oxide; Genome Wide Association Study
9.  Relationship between systemic and cerebral vascular disease and brain structure integrity in normal elderly individuals 
Cerebral white matter lesions (WMLs) are considered a reflection of cerebral and systemic small vessel disease (SVD), and are associated with reductions in brain volume. Like the brain, the kidney is also sensitive to factors that affect vasculature. Glomerular dysfunction due to renal vascular damage can be measured with different biochemical parameters, such as creatinine or cystatin C, although cystatin C is considered to be more accurate than creatinine in the elderly. The purpose of the study was to determine whether manifestations of SVD in the kidney can predict SVD-based damage to the brain. We examined the relationship between glomerular dysfunction as a measure of SVD on WMLs, gray matter (GM) volume, and cognition in 735 cognitively normal participants from the Cardiovascular Health Study Cognition Study. The multivariate analyses controlled for demographic characteristics, hypertension, heart disease, diabetes, Apolipoprotein 4 allele, C reactive protein, lipids, physical activity, smoking, and body mass index (BMI). Elevated cystatin C levels were associated with lower neuropsychological test scores, the presence of MRI-identified brain infarcts, the severity of WMLs, and GM atrophy five years later. In adjusted models, GM volume was significantly associated with cystatin-C only until BMI and severity of WMLs were added to the model, meaning that the effect of SVD on GM volume is mediated by these two variables. These findings suggest that age-related SVD is a process that leads to altered brain structure, and creates a vulnerability state for cognitive decline.
doi:10.3233/JAD-141077
PMCID: PMC4297227  PMID: 25213770
Cystatin C; gray matter volume; cognitive impairment; white matter lesions
10.  Testosterone and Dihydrotestosterone and Incident Ischemic Stroke in Men in the Cardiovascular Health Study 
Clinical endocrinology  2014;81(5):746-753.
Summary
Objective
Ischemic stroke is a major cause of morbidity and mortality in elderly men. Our main objective was to examine if testosterone (T) or dihydrotestosterone (DHT) were associated with incident ischemic stroke in elderly men.
Design
Cohort study
Participants
Elderly men in the Cardiovascular Health Study who had no history of stroke, heart disease, or prostate cancer as of 1994 and were followed until December 2010.
Measurements
Adjudicated ischemic stroke
Results
Among 1032 men (mean age 76, range 66-97), followed for a median of 10 years, 114 had an incident ischemic stroke. Total T and free T were not significantly associated with stroke risk while DHT had a nonlinear association with incident stroke (p=.006) in analyses adjusted for stroke risk factors. The lowest risk for stroke was at DHT levels of 50-75 ng/dL, with greater risk for stroke at DHT levels above 75 ng/dl or below 50ng/dl. Results were unchanged when SHBG was added to the model. Calculated free DHT had an inverse linear association with incident ischemic stroke with HR 0.77 (95% CI, 0.61, 0.98) per standard deviation in analyses adjusted for stroke risk factors.
Conclusions
DHT had a nonlinear association with stroke risk in which there was an optimal DHT level associated with the lowest stroke risk. Further studies are needed to confirm these results and to clarify if there is an optimal androgen range associated with the least risk for adverse outcomes in elderly men.
doi:10.1111/cen.12452
PMCID: PMC4169352  PMID: 24645738
androgens; testosterone; dihydrotestosterone; stroke; cohort
11.  Formulations of hormone therapy and risk of Parkinson disease 
Background
Hormone therapy (HT) is a class of medications widely prescribed to women in the Western world. Evidence from animal models and in vitro studies suggests that estrogen may protect against nigrostriatal system injury and increase dopamine synthesis, metabolism, and transport. Existing epidemiologic research indicates a possible reduced risk of Parkinson disease (PD) associated with HT use. The objective of this study was to evaluate PD risk associated with specific HT formulations.
Methods
Neurologist confirmed cases and age-matched controls were identified from Group Health Cooperative (GHC) of Washington state. Final analysis included 137 female cases and 227 controls. HT use was ascertained from the GHC pharmacy database, further classified as conjugated estrogens, esterified estrogens, and progestin.
Results
Ever use of HT formulation demonstrated a suggested elevated risk with esterified estrogen use (OR, 3.1; 95% CI, 1.0–9.8), and no risk associated with conjugated estrogen use (OR, 0.6; 95% CI, 0.6–1.3). Restricting this analysis to prescriptions that included progestin further elevated the risk associated with esterified estrogen use (OR, 6.9; 95% CI, 2.1–22.9); again, no risk was associated with conjugated estrogen use (OR, 1.7; 95% CI, 0.6–5.0).
Conclusions
The findings from this study suggest an increase in PD risk associated with esterified estrogen use combined with progestin, and no risk associated with conjugated estrogen with progestin. These findings could have important implications for choice of HT in clinical practice.
doi:10.1002/mds.26037
PMCID: PMC4216612  PMID: 25255692
hormone therapy; estrogen therapy; Parkinson disease; neurodegenerative disease; epidemiology
12.  Acute Kidney Injury is Associated with Increased Hospital Mortality after Stroke 
Background
Acute kidney injury (AKI) is common and associates with poor clinical outcomes. Information about the incidence of AKI and effect on stroke outcomes is limited.
Methods
Data were analyzed from a registry of subjects with ischemic stroke and intracerebral hemorrhage (ICH) hospitalized at a single academic medical center. Admission creatinine was considered to be the baseline. AKI was defined as a creatinine increase of 0.3 mg/dL or a percentage increase of at least 50% from baseline, occurring during hospitalization. Multivariate logistic regression models were created for both stroke types, with hospital mortality as the outcome. Covariates included gender, race, age, admission creatinine, admission NIH Stroke Scale score, performance of contrast-enhanced CT scan of the head and neck, and medical co-morbidities.
Results
There were 528 cases of ischemic stroke with 70 deaths (13%), and 829 cases of ICH with 268 deaths (32%). The mean age was 64 years, with 56% men and 71% whites. AKI complicated 14% of ischemic stroke and 21% of ICH hospitalizations. In multivariate analysis stratified by stroke type, AKI was associated with increased hospital mortality from ischemic stroke (odds ratio (OR) 3.08, 95% confidence interval (CI) [1.49–6.35]) but not ICH (OR 0.82, 95% CI [0.50–1.35]), except for those surviving at least two days (OR 2.11, 95% CI [1.18–3.77]).
Conclusions
AKI occurs frequently after stroke and is associated with increased hospital mortality. Further studies are needed to establish if the association is causal and if measures to prevent AKI would result in decreased mortality.
doi:10.1016/j.jstrokecerebrovasdis.2012.06.005
PMCID: PMC3507321  PMID: 22818389
13.  Association of Cardiac Annular / Valvular Calcification with Brain Findings on Magnetic Resonance Imaging in Community Dwelling Older Adults: the Cardiovascular Health Study 
Objective
The objective of this study is to investigate the association of mitral annular calcification (MAC), aortic annular calcification (AAC), and aortic valve sclerosis (AVSc) with covert magnetic resonance imaging (MRI)-defined brain infarcts.
Background
Clinically silent brain infarcts defined by MRI are associated with increased risk of cognitive decline, dementia, and future overt stroke. Left sided cardiac valvular / annular calcifications are suspected as risk factors for clinical ischemic stroke.
Methods
2,680 Cardiovascular Health Study participants without clinical history of stroke or transient ischemic attack underwent both brain MRI (1992–93) and echocardiography (1994–95).
Results
The mean age of the participants was 74.5 years ± 4.8 and 39.3% were men. The presence of any annular / valvular calcification (either MAC or AAC or AVSc), MAC alone, or AAC alone were significantly associated with a higher prevalence of covert brain infarcts in unadjusted analyses (p < 0.01 for all). In models adjusted for age, sex, race, body mass index, physical activity, creatinine, systolic blood pressure, total cholesterol, HDL-cholesterol, smoking, diabetes, coronary heart disease, and congestive heart failure, the presence of any annular / valve calcification remained associated with covert brain infarcts [RR 1.24 (95% CI 1.05, 1.47)]. The degree of annular / valvular calcification severity showed a direct relation with the presence of covert MRI findings.
Conclusion
Left-sided cardiac annular / valvular calcification are associated with covert MRI-defined brain infarcts. Further study is warranted to identify mechanisms and determine whether intervening on the progression of annular / valvular calcification could reduce the incidence of covert brain infarcts as well as the associated risk of cognitive impairment and future stroke.
doi:10.1016/j.jacc.2011.01.034
PMCID: PMC4104125  PMID: 21596233
Covert Brain Infarcts; Aortic Valve; Mitral Valve; Calcification; Epidemiology
14.  Atrial fibrillation and cognitive decline 
Neurology  2013;81(2):119-125.
Objective:
We sought to determine whether in the absence of clinical stroke, people with atrial fibrillation experience faster cognitive decline than people without atrial fibrillation.
Methods:
We conducted a longitudinal analysis in the Cardiovascular Health Study, a community-based study of 5,888 men and women aged 65 years and older, enrolled in 1989/1990 or 1992/1993. Participants did not have atrial fibrillation or a history of stroke at baseline. Participants were censored when they experienced incident clinical stroke. Incident atrial fibrillation was identified by hospital discharge diagnosis codes and annual study ECGs. The main outcome was rate of decline in mean scores on the 100-point Modified Mini-Mental State Examination (3MSE), administered annually up to 9 times.
Results:
Analyses included 5,150 participants, of whom 552 (10.7%) developed incident atrial fibrillation during a mean of 7 years of follow-up. Mean 3MSE scores declined faster after incident atrial fibrillation compared with no prior atrial fibrillation. For example, the predicted 5-year decline in mean 3MSE score from age 80 to age 85 was −6.4 points (95% confidence interval [CI]: −7.0, −5.9) for participants without a history of atrial fibrillation, but was −10.3 points (95% CI: −11.8, −8.9) for participants experiencing incident atrial fibrillation at age 80, a 5-year difference of −3.9 points (95% CI: −5.3, −2.5).
Conclusions:
In the absence of clinical stroke, people with incident atrial fibrillation are likely to reach thresholds of cognitive impairment or dementia at earlier ages than people with no history of atrial fibrillation.
doi:10.1212/WNL.0b013e31829a33d1
PMCID: PMC3770176  PMID: 23739229
15.  Early diagnosis and treatment of obstructive sleep apnea after stroke 
Neurology: Clinical Practice  2013;3(3):192-201.
Summary
Sleep-disordered breathing is an increasingly recognized disorder that is particularly prevalent among stroke patients. Obstructive sleep apnea, a form of sleep-disordered breathing, is associated with multiple major stroke risk factors but is also an independent risk factor for stroke. In addition, untreated sleep apnea is associated with poor functional outcome after stroke. Sleep apnea is amenable to treatment and should be considered a modifiable stroke risk factor, though long-term compliance remains a major barrier. A better understanding of the relationship between sleep apnea and stroke may prompt providers to pursue the early diagnosis and treatment of underlying sleep-disordered breathing to both improve the chance of recovery from stroke in the short term and to reduce the risk of recurrent stroke in the long term.
doi:10.1212/CPJ.0b013e318296f274
PMCID: PMC3721244  PMID: 23914326
16.  Neighborhood socioeconomic disadvantage and mortality after stroke 
Neurology  2013;80(6):520-527.
Objective:
Residence in a socioeconomically disadvantaged community is associated with mortality, but the mechanisms are not well understood. We examined whether socioeconomic features of the residential neighborhood contribute to poststroke mortality and whether neighborhood influences are mediated by traditional behavioral and biologic risk factors.
Methods:
We used data from the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ≥65 years. Residential neighborhood disadvantage was measured using neighborhood socioeconomic status (NSES), a composite of 6 census tract variables representing income, education, employment, and wealth. Multilevel Cox proportional hazard models were constructed to determine the association of NSES to mortality after an incident stroke, adjusted for sociodemographic characteristics, stroke type, and behavioral and biologic risk factors.
Results:
Among the 3,834 participants with no prior stroke at baseline, 806 had a stroke over a mean 11.5 years of follow-up, with 168 (20%) deaths 30 days after stroke and 276 (34%) deaths at 1 year. In models adjusted for demographic characteristics, stroke type, and behavioral and biologic risk factors, mortality hazard 1 year after stroke was significantly higher among residents of neighborhoods with the lowest NSES than those in the highest NSES neighborhoods (hazard ratio 1.77, 95% confidence interval 1.17–2.68).
Conclusion:
Living in a socioeconomically disadvantaged neighborhood is associated with higher mortality hazard at 1 year following an incident stroke. Further work is needed to understand the structural and social characteristics of neighborhoods that may contribute to mortality in the year after a stroke and the pathways through which these characteristics operate.
doi:10.1212/WNL.0b013e31828154ae
PMCID: PMC3589286  PMID: 23284071
17.  Neighborhood Disadvantage and Ischemic Stroke: The Cardiovascular Health Study (CHS) 
Background and Purpose
Neighborhood characteristics may influence the risk of stroke and contribute to socioeconomic disparities in stroke incidence. The objectives of this study were to examine the relationship between neighborhood socioeconomic status (NSES) and incident ischemic stroke and examine potential mediators of these associations.
Methods
We analyzed data from 3834 whites and 785 African Americans enrolled in the Cardiovascular Health Study, a multicenter, population-based, longitudinal study of adults ages ≥65 years from four U.S. counties. The primary outcome was adjudicated incident ischemic stroke. NSES was measured using a composite of six census tract variables. Race-stratified multilevel Cox proportional hazard models were constructed, adjusted for sociodemographic, behavioral, and biologic risk factors.
Results
Among whites, in models adjusted for sociodemographic characteristics, stroke hazard was significantly higher among residents of neighborhoods in the lowest compared to the highest NSES quartile (Hazard Ratio [HR] =1.32; 95% CI 1.01-1.72), with greater attenuation of the HR after adjustment for biologic risk factors (HR=1.16; 0.88-1.52) than for behavioral risk factors (HR=1.30; 0.99-1.70). Among African Americans, we found no significant associations between NSES and ischemic stroke.
Conclusions
Higher risk of incident ischemic stroke was observed in the most disadvantaged neighborhoods among whites, but not among African Americans. The relationship between NSES and stroke among whites appears to be mediated more strongly by biologic than behavioral risk factors.
doi:10.1161/STROKEAHA.111.622134
PMCID: PMC3781011  PMID: 21940966
18.  Symptoms and Risk Factors for Stroke in a Community-Based Observational Sample in Viet Nam 
Background
Viet Nam is experiencing a health transition from infectious to chronic disease. Data on cardiovascular diseases, including strokes, are limited.
Methods
Data were randomly collected from six communities in Da Nang, Viet Nam, on participant demographics, medical history, blood pressure, anthropometrics and health behavior using World Health Organization (WHO) guidelines. Stroke symptoms were collected by self-report with the standardized Questionnaire for Verifying Stroke Free Status. Multivariate logistic regression was used to identify factors associated with the presence of stroke symptoms.
Results
1,621 adults were examined with a mean age of 52.0 years (± 12.5 years), of which 56.1% were women. 27.3% of the participants were found to have hypertension, 26.2% used tobacco, and 16.1% were overweight. More than two-thirds of the participants with hypertension were unaware of their condition. Almost one fourth of the participants were identified by the questionnaire as previously experiencing at least one stroke symptom. Age, rural residence, and education were associated with the presence of stroke symptoms. Models adjusted for demographics found hypertension, high cholesterol, reported severe chest pain, former smoking, and being overweight to be associated with a higher prevalence of stroke symptoms.
Conclusions
The high frequency of stroke symptoms in Da Nang calls for further evaluation and interventions to reduce hypertension and other risk factors for chronic disease.
doi:10.1016/j.jegh.2012.06.001
PMCID: PMC3607634  PMID: 23538875
stroke; symptoms; Viet Nam; community-based; risk factors
19.  Common variants at 6q22 and 17q21 are associated with intracranial volume 
Nature genetics  2012;44(5):539-544.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study in 8,175 community-dwelling elderly did not reveal any genome-wide significant associations (p<5*10−8) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (p=3.4*10−11), a known height locus on chromosome 6q22, and rs9915547, tagging the inversion on chromosome 17q21 (p=1.5*10−12). We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 older persons (p=1.1*10−3 for 6q22 and p=1.2*10−3 for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age 14.5 months). Our data identify two loci associated with head size, with the inversion on 17q21 also likely involved in attaining maximal brain size.
doi:10.1038/ng.2245
PMCID: PMC3618290  PMID: 22504418
20.  Birth Order and Narcolepsy Risk Among Genetically Susceptible Individuals: a Population-based Case-control Study 
Sleep Medicine  2012;13(3):310-313.
Background
Birth order may play a role in autoimmune diseases and early childhood infections, both factors implicated in the etiology of narcolepsy. We investigated the association between birth order and narcolepsy risk in a population-based case-control study in which all study subjects were HLA-DQB1*0602 positive.
Methods
Subjects were 18-50 years old, residents of King County, Washington, and positive for HLA-DQB1*0602. Birth order was obtained from administered interviews. We used logistic regression to generate odds ratios adjusted for income and African American race.
Results
Analyses included 67 cases (mean age 34.3 [SD=9.1], 70.2% female) and 95 controls (mean age 35.1 [SD=8.8], 58.1% female). Associations for birth order were as follows: First born (cases 38.8% vs. controls 50.2%, OR=1.0; Reference), second born (cases 29.9% vs. controls 32.9%, OR=1.6; 95% CI 0.7, 3.7), third born or higher (cases 31.3% vs. controls 16.8%, OR=2.5; 95% CI 1.0, 6.0). A linear trend was significant (p<0.05). Sibling number, sibling gender, having children, and number of children did not differ significantly between narcolepsy cases and controls.
Conclusions
Narcolepsy risk was significantly associated with higher birth order in this population-based study of genetically susceptible individuals. This finding supports an environmental influence on narcolepsy risk through an autoimmune mechanism, early childhood infections, or both.
doi:10.1016/j.sleep.2011.09.010
PMCID: PMC3288144  PMID: 22281000
Narcolepsy; Birth order; HLA-DQB1*0602; genetics; autoimmune
21.  Markers of Inflammation in Prevalent and Incident Parkinson’s Disease in the Cardiovascular Health Study 
Parkinsonism & related disorders  2011;18(3):274-278.
Background
Studies demonstrate existence of inflammation in prevalent Parkinson’s disease (PD). We assessed associations of baseline levels of inflammatory markers with prevalent PD at baseline (1989) and incident PD identified over 13 years of follow-up of the Cardiovascular Health Study.
Methods
Blood samples at baseline were measured for fibrinogen, interleukin-6, tumor necrosis factor–α, C-reactive protein, albumin, and white blood cells. The analysis included 60 prevalent and 154 incident PD cases.
Results
Risk of prevalent PD was significantly higher per doubling of IL-6 among women (odds ratio [OR] = 1.5, 95% confidence interval [CI]: 1.0, 2.4) and WBC among men (OR: 2.4, 95% CI: 1.2, 4.9) in multivariate models. Risk of incident PD was not associated with higher levels of any biomarker after adjusting for age, smoking, African American race, and history of diabetes. Inverse associations with incident PD were observed per doubling of C-reactive protein (OR=0.9; 95% CI: 0.8, 1.0) and of fibrinogen among women (OR=0.4; 95% CI: 0.2, 0.8).
Conclusions
Although inflammation exists in PD, it may not represent an etiologic factor. Our findings suggest the need for larger studies that measure inflammatory markers before PD onset.
doi:10.1016/j.parkreldis.2011.11.003
PMCID: PMC3288759  PMID: 22119505
albumins; C-reactive protein; inflammation; interleukin-6; odds ratio; Parkinson’s disease; tumor necrosis factor-α
22.  Gender Differences in Tea, Coffee, and Cognitive Decline in the Elderly: The Cardiovascular Health Study 
Although caffeine can enhance cognitive function acutely, long-term effects of consumption of caffeine-containing beverages such as tea and coffee are uncertain. Data on 4,809 participants aged 65 and older from the Cardiovascular Health Study (CHS) were used to examine the relationship of consumption of tea and coffee, assessed by food frequency questionnaire, on change in cognitive function by gender. Cognitive performance was assessed using serial Modified Mini-Mental State (3MS) examinations, which were administered annually up to 9 times. Linear mixed models were used to estimate rates of change in standard 3MS scores and scores modeled using item response theory (IRT). Models were adjusted for age, education, smoking status, clinic site, diabetes, hypertension, stroke, coronary heart disease, depression score, and APOE genotype. Over the median 7.9 years of follow-up, participants who did not consume tea or coffee declined annually by an average of 1.30 points (women) and 1.11 points (men) on standard 3MS scores. In fully adjusted models using either standard or IRT 3MS scores, we found modestly reduced rates of cognitive decline for some, but not all, levels of coffee and tea consumption for women, with no consistent effect for men. Caffeine consumption was also associated with attenuation in cognitive decline in women. Dose-response relationships were not linear. These longitudinal analyses suggest a somewhat attenuated rate of cognitive decline among tea and coffee consumers compared to non-consumers in women but not in men. Whether this association is causal or due to unmeasured confounding requires further study.
doi:10.3233/JAD-2011-110431
PMCID: PMC3577072  PMID: 21841254
Caffeine; coffee; cognition; tea
23.  Environmental tobacco smoke and Parkinson disease 
Movement Disorders  2011;27(2):293-297.
Background
Parkinson disease is inversely associated with cigarette smoking, but its relation with passive smoking or environmental tobacco smoke exposure is rarely examined.
Methods
Within a case-control study we assessed the association between Parkinson disease and living or working with active smokers. Cases were newly diagnosed with idiopathic Parkinson disease (N=154) from western Washington State in 2002–2008. Age- and sex-matched controls (N=173) were neurologically normal and unrelated to cases.
Results
Compared with never active or passive tobacco smokers, we observed similarly reduced Parkinson disease risks for ever passive smokers only (odds ratio=0.34, 95% confidence interval 0.16–0.73) as for ever active smokers (0.35, 0.17–0.73). Among persons whose only tobacco smoke exposure was passive smoking at home, risk was inversely associated with years exposed.
Conclusion
These observations parallel those well-established for active smoking. However, it remains unresolved whether a true protective effect of tobacco smoke, generally detrimental to health, underlies these associations.
doi:10.1002/mds.24012
PMCID: PMC3289937  PMID: 22095755
Environmental Tobacco Smoke Pollution; Idiopathic Parkinson Disease; Passive Smoking; Smoking
24.  Mid- and Late-Life Obesity: Risk of Dementia in the Cardiovascular Health Cognition Study 
Archives of neurology  2009;66(3):336-342.
Objectives
To evaluate associations between mid- and late-life obesity and risk of dementia.
Design
Prospective cohort followed 5.4 years from 1992/4 through 1999.
Setting
Community-dwelling sample in four US sites recruited from Medicare eligibility files.
Participants
2,798 adults without dementia, mean age 74.7 years, 59.1% women, participating in the Cardiovascular Health Cognition Study completing a magnetic resonance image, measured for height and weight at baseline (late-life) and self-reporting weight at age 50 (mid-life). Body mass index (BMI) was calculated at both times.
Main Outcome Measures
Dementia, Alzheimer’s disease (AD) and vascular dementia (VaD) classified by a multidisciplinary committee using standardized criteria.
Results
Classification resulted in 480 persons with incident dementia, 245 with AD (no VaD) and 213 with VaD (with or without AD). In evaluations of mid-life obesity, an increased risk of dementia was found for obese (BMI >30) compared to normal (BMI 20-25) persons adjusted for demographics (HR: 1.39, 95% CI: 1.03-1.87) and for caradiovascularl risk factors (HR: 1.36, 95% CI: 0.94-1.95). The risk estimates reversed in assessments of late-life BMI. Underweight persons (BMI < 20) had an increased risk of dementia (HR: 1.62, 95% CI: 1.02-2.64) while being overweight (BMI 25-30) was not associated (HR: 0.92, 95% CI: 0.72-1.18) and being obese reduced the risk of dementia (HR: 0.63, 95% CI: 0.44-0.91) compared to those with normal BMI.
Conclusions
These results help explain the “obesity paradox” as differences in dementia risk over time are consistent with physical changes in the trajectory toward disability.
doi:10.1001/archneurol.2008.582
PMCID: PMC3513375  PMID: 19273752
25.  Common variants at 12q14 and 12q24 are associated with hippocampal volume 
Bis, Joshua C. | DeCarli, Charles | Smith, Albert Vernon | van der Lijn, Fedde | Crivello, Fabrice | Fornage, Myriam | Debette, Stephanie | Shulman, Joshua M. | Schmidt, Helena | Srikanth, Velandai | Schuur, Maaike | Yu, Lei | Choi, Seung-Hoan | Sigurdsson, Sigurdur | Verhaaren, Benjamin F.J. | DeStefano, Anita L. | Lambert, Jean-Charles | Jack, Clifford R. | Struchalin, Maksim | Stankovich, Jim | Ibrahim-Verbaas, Carla A. | Fleischman, Debra | Zijdenbos, Alex | den Heijer, Tom | Mazoyer, Bernard | Coker, Laura H. | Enzinger, Christian | Danoy, Patrick | Amin, Najaf | Arfanakis, Konstantinos | van Buchem, Mark A. | de Bruijn, Renée F.A.G. | Beiser, Alexa | Dufouil, Carole | Huang, Juebin | Cavalieri, Margherita | Thomson, Russell | Niessen, Wiro J. | Chibnik, Lori B. | Gislason, Gauti K. | Hofman, Albert | Pikula, Aleksandra | Amouyel, Philippe | Freeman, Kevin B. | Phan, Thanh G. | Oostra, Ben A. | Stein, Jason L. | Medland, Sarah E. | Vasquez, Alejandro Arias | Hibar, Derrek P. | Wright, Margaret J. | Franke, Barbara | Martin, Nicholas G. | Thompson, Paul M. | Nalls, Michael A. | Uitterlinden, Andre G. | Au, Rhoda | Elbaz, Alexis | Beare, Richard J. | van Swieten, John C. | Lopez, Oscar | Harris, Tamara B. | Chouraki, Vincent | Breteler, Monique M.B. | De Jager, Philip L. | Becker, James T. | Vernooij, Meike W. | Knopman, David | Fazekas, Franz | Wolf, Philip A. | van der Lugt, Aad | Gudnason, Vilmundur | Longstreth, W.T. | Brown, Mathew A. | Bennett, David A. | van Duijn, Cornelia M. | Mosley, Thomas H. | Schmidt, Reinhold | Tzourio, Christophe | Launer, Lenore J. | Ikram, M. Arfan | Seshadri, Sudha
Nature genetics  2012;44(5):545-551.
Aging is associated with reductions in hippocampal volume (HV) that are accelerated by Alzheimer’s disease and vascular risk factors. Our genome-wide association study of dementia-free persons (n=9,232) identified 46 SNPs at four loci with p-values <4.0×10-7. Two additional samples (n=2,318) replicated associations at 12q24 within MSRB3/WIF1 (discovery + replication, rs17178006; p=5.3×10-11) and at 12q14 near HRK/FBXW8 (rs7294919; p=2.9×10-11). Remaining associations included one 2q24 SNP within DPP4 (rs6741949; p=2.9×10-7) and nine 9p33 SNPs within ASTN2 (rs7852872; p=1.0×10-7) that were also associated with HV (p<0.05) in a third younger, more heterogeneous sample (n=7,794). The ASTN2 SNP was also associated with decline in cognition in a largely independent sample (n=1,563). These associations implicate genes related to apoptosis (HRK), development (WIF1), oxidative stress (MSR3B), ubiquitination (FBXW8), enzymes targeted by new diabetes medications (DPP4), and neuronal migration (ASTN2), indicating novel genetic influences that influence hippocampal size and possibly the risk of cognitive decline and dementia.
doi:10.1038/ng.2237
PMCID: PMC3427729  PMID: 22504421

Results 1-25 (72)