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.
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).
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.
A low intake of cholesterol, particularly in the presence of high iron, may be associated with an increased risk for PD.
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.
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.
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.
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.
Viet Nam is experiencing a health transition from infectious to chronic disease. Data on cardiovascular diseases, including strokes, are limited.
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.
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.
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.
stroke; symptoms; Viet Nam; community-based; risk factors
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.
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.
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.
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.
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.
Narcolepsy; Birth order; HLA-DQB1*0602; genetics; autoimmune
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.
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.
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).
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.
albumins; C-reactive protein; inflammation; interleukin-6; odds ratio; Parkinson’s disease; tumor necrosis factor-α
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.
Caffeine; coffee; cognition; tea
Parkinson disease is inversely associated with cigarette smoking, but its relation with passive smoking or environmental tobacco smoke exposure is rarely examined.
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.
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.
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.
Environmental Tobacco Smoke Pollution; Idiopathic Parkinson Disease; Passive Smoking; Smoking
To evaluate associations between mid- and late-life obesity and risk of dementia.
Prospective cohort followed 5.4 years from 1992/4 through 1999.
Community-dwelling sample in four US sites recruited from Medicare eligibility files.
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.
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.
These results help explain the “obesity paradox” as differences in dementia risk over time are consistent with physical changes in the trajectory toward disability.
Studies suggest an inverse association between urate concentration and the risk of Parkinson disease (PD). We investigated this in the Cardiovascular Health Study in an elderly community-based cohort of adults.
The association of baseline urate (μmol/l) and incident PD over 14 years was assessed with locally weighted scatterplot smoothing (LOESS) regression from which categories of low (<300 μmol/l), middle (300–500 μmol/l), and high (>500 μmol/l) urate ranges were derived. Multivariate logistic regression models assessed the risk of PD for each urate range. Linear and quadratic terms were tested when modeling the association between urate and the risk of PD.
Women had significantly lower urate concentrations than did men [316.8 μmol/l (SD 88.0) vs. 367.4 μmol/l (SD 87.7), p < 0.0001] and in women no associations between urate and PD risk were observed. In men, LOESS curves suggested a U-shaped or threshold effect between urate and PD risk. With the middle range as reference, the risk of developing PD was significantly increased for urate <300 μmol/l (OR 1.69, 95% CI 1.03–2.78) but not for urate >500 μmol/l (OR 1.55, 95% CI 0.72–3.32) in men. A negative linear term was significant for urate <500 μmol/l, and across the entire range a convex quadratic term was significant.
Results suggest a more complex relationship than previously reported between urate levels and the risk of PD in men. Low urate concentrations were associated with a higher PD risk and high urate concentrations were not associated with a further decrease in PD risk.
Parkinson disease; Risk factors; Oxidative stress; Epidemiology; Uric acid
Parkinson’s disease (PD) has been associated with various workplace factors, but the evidence is inconsistent.
To estimate the risk of PD associated with various jobs and workplace exposures.
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.
Risk was not significantly affected by farming work, by metal work, or by exposure to pesticides, metals, or solvents.
These findings do not provide support for the hypothesis that workplace factors affect the risk of PD.
risk factors in epidemiology; Parkinson’s disease/parkinsonism; toxicology; occupational; human
Although ongoing cohort studies offer a unique opportunity to apply existing information collected prospectively to further the scientific understanding of Parkinson's disease (PD), they typically have limited information for clinical diagnosis.
We used combinations of self-report, International Classification of Diseases − 9th edition codes and antiparkinsonian medications to identify PD in the Cardiovascular Health Study. To determine whether the expected inverse association between smoking and PD is evident using our outcome definitions, we assessed baseline smoking characteristics for various definitions of PD.
We identified 60 cases with prevalent PD (1.0%; 95% confidence interval, CI = 0.8–1.3%) and 154 with incident PD by year 14. Clear associations were observed for current smokers (odds ratio, OR = 0.50; 95% CI = 0.26–0.95) and for those who smoked ≥50 pack-years (OR = 0.53; 95% CI = 0.29–0.96). Estimates for smoking were similar when ≥2 data sources were required. Estimates for self-report alone were attenuated towards null.
Using multiple data sources to identify PD represents an alternative method of outcome identification in a cohort that would otherwise not be possible for PD research. Ongoing cohort studies can provide settings in which rapid replication and explorations of new hypotheses for PD are possible.
Cardiovascular Health Study; Cohort study; Epidemiology; International Classification of Diseases, 9th edition; Smoking; Parkinson's disease
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.
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.
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.
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.
= atrial fibrillation;
= Cardiovascular Health Study;
= confidence interval;
= estimated glomerular filtration rate;
= hazard ratio;
= left ventricular hypertrophy;
= urinary albumin-to-creatinine ratio.
Two simple questions have been used to classify neurologic outcome in patients with stroke. Could they be similarly applied to patients with cardiac arrest?
As part of a randomized trial, study personnel interviewed by telephone survivors of out-of-hospital cardiac arrest to assess their outcomes three months after discharge. They asked two simple questions: 1) In the last two weeks, did you require help from another person for your everyday activities? & 2) Do you feel that you have made a complete mental recovery form your heart arrest? Next they administered the Mini-Mental State Examination (MMSE) from the Adult Lifestyles and Function Interview (ALFI) to assess cognition on a scale from 0 to 22 and the Health Utilities Index Mark 3 (HUI3) to assess quality of life on a scale from 0 (death) to 1 (perfect health).
Based on responses to the two simple questions, 32 survivors were classified as dependent (n=5, 16%), independent (n=3, 9%) and full recovery (n=24, 75%). The mean ALFI-MMSE score was 19.1 (standard deviation 5.1), and the mean HUI3 score was 0.76 (standard deviation 0.28). The classification based on the two simple questions was significantly correlated with ALFI-MMSE (p=0.002) and HUI3 (p=0.001). Scores for the HUI3 were missing in 8 survivors.
Neurologic outcomes based on the two simple questions after cardiac arrest can be easily determined, sensibly applied, and readily interpreted. These preliminary findings justify further evaluation of this simple and practical approach to classify neurologic outcome in survivors of cardiac arrest.
heart arrest; out-of-hospital CPR; outcome; quality of life
Thrombosis and inflammation are critical in stroke etiology, but associations of coagulation and inflammation gene variants with stroke, and particularly factor VII levels are inconclusive.
To test the associations between 736 single nucleotide polymorphisms (SNP) between tagging haplotype patterns of 130 coagulation and inflammation genes, and stroke events in the 5,888 participants ≥ 65 of the observational Cardiovascular Health Study cohort.
/Methods: With 16 years of follow-up, age and sex-adjusted Cox models were used to estimate associations of SNPs and factor VIIc levels with future stroke.
815 strokes occurred in 5,255 genotyped participants without baseline stroke (748 ischemic strokes, 586 among whites). Among whites, 6 SNPs were associated with stroke with a nominal p <0.01: rs6046 and rs3093261 (F7 gene); rs4918851 and rs3781387 (HABP2 gene); rs3138055 (NFKB1A) and rs4648004 (NFKB1). Two of these SNPs were associated with factor VIIc levels (units = percent activity): rs6046 (β = −18.5, p = 2.38 × 10−83) and rs3093261 (β = 2.99, p = 3.93 × 10−6). Adjusting for age, sex, race, and cardiovascular risk factors, the association of factor VIIc quintiles (Q) with stroke were (HR: 95% CI): Q1 (reference); Q2 (1.4; 1.1, 1.9); Q3 (1.1; 0.8, 1.5); Q4 (1.5; 1.1, 2.0); Q5 (1.6; 1.2, 2.2). Associations between SNPs and stroke were independent of factor VIIc levels.
Variation in factor VII-related genes and factor VIIc levels were associated with risk of incident ischemic stroke in this elderly cohort, suggesting a potential causal role for factor VII in stroke etiology.
Stroke; Genetic Epidemiology; factor VII; hemostasis; inflammation; cardiovascular disease risk
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.
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).
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.
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.
brain infarction; cerebrovascular accident; epidemiology; genetics; prevention; risk factors
We examined the risk of narcolepsy associated with active and passive smoking among genetically susceptible individuals.
We conducted a population-based case-control study in King County, Wash., USA. Between 2001 and 2005, we enrolled 67 cases through physicians and public outreach, and 95 controls through random-digit dialing. Subjects were aged between 18 and 50 years and positive for HLA DQB1*0602. All subjects were administered in-person interviews about their history of active and passive smoking.
We observed an increased risk of narcolepsy associated with having lived with two or more household smokers (odds ratio, OR = 5.1; 95% confidence interval, CI: 1.6, 12.1); with a grandparent or a sibling who smoked (OR = 3.0; 95% CI: 1.1, 8.3); with a non-family household member who smoked (OR = 3.7; 95% CI: 1.6, 8.6); and with an unrelated smoker for 1–2 years (OR = 3.1; 95% CI: 1.0, 9.0). The risk of narcolepsy was not associated with exposure to smoke at work or with active smoking before age 21 or before age of narcolepsy onset.
Passive smoking may be a risk factor for narcolepsy in subjects with HLA DQB1*0602. Future studies could help clarify whether passive smoking is an important etiologic component of narcolepsy among genetically susceptible individuals.
Case-control study; Epidemiology; HLA-DQ antigens; Narcolepsy; Smoking
To investigate the association between fish consumption and subclinical brain abnormalities.
In the population-based Cardiovascular Health Study, 3,660 participants age ≥65 underwent an MRI scan in 1992–1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses.
After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish ≥3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54–1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities.
Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.
= absolute risk reduction;
= body mass index;
= coronary heart disease;
= Cardiovascular Health Study;
= docosahexaenoic acid;
= eicosapentaenoic acid;
= food frequency questionnaire;
= high-density lipoprotein cholesterol;
= low-density lipoprotein cholesterol;
= polyunsaturated fatty acid;
= relative risk.
To compare human T-cell lymphotrophic virus type I (HTLV-I) seropositive and seronegative women for symptoms and signs of spasticity.
Infection with HTLV-I causes tropical spastic paraparesis/ HTLV-I–associated myelopathy (TSP/HAM). Certain populations, including female commercial sex workers (FSW), are at increased risk of developing this infection. Fewer than 5% of HTLV-I–seropositive persons develop TSP/HAM, which is typically associated with spasticity.
Cross-sectional study of 255 registered FSW in Callao, Perú, involving a questionnaire detailing demographics and neurologic symptoms, standard neurologic examination, quantitative assessment of spasticity (QSA) of muscle tone, and serologic testing for HTLV-I. Participants and examiners were blinded to serology results.
On the questionnaire and neurologic examination, none of the 32 HTLV-I–seropositive or 223 seronegative women had signs or symptoms of spasticity. However, mean values on QSA were significantly higher among seropositive women (27.1 Newton-meters/radian [N-m/r]) than among seronegative women (21.6 N-m/r, p = 0.01), indicating a subclinical increase in lower extremity tone. With values of QSA divided into tertiles, and the first tertile serving as the comparison group, the odds ratio for seropositivity was 1.4 (95% confidence interval [CI] 1.0 to 2.0) in the second and 3.1 (95% CI 2.2 to 4.3) in the third tertile, after adjusting for age and place of birth.
Although a standard neurologic evaluation could not distinguish between women with and without HTLV-I infection, QSA indicated significantly increased lower extremity tone in those with infection. Long-term follow-up will determine whether these subclinical findings in asymptomatic women progress to overt TSP/HAM.
Atrial fibrillation (AF) is a common arrhythmia that affects over 2 million people in the United States. We sought to determine whether the risk of incident AF among patients treated for hypertension differs by the degree of blood pressure control.
A population based, case-control study of 433 patients with verified incident AF and 899 controls was conducted to investigate the relationship between average achieved systolic (SBP) and diastolic (DBP) blood pressure and risk of AF. All patients were members of an integrated health care delivery system and were pharmacologically treated for hypertension. Medical records were reviewed to confirm the diagnosis of new onset AF and to collect information on medical conditions, health behaviors, and measured blood pressures. Average achieved SBP and DBP were calculated from the three most recent outpatient blood pressure measurements.
Compared with the reference level of 120-129 mm Hg, for categories of average achieved SBP of <120, 130-139, 140-149, 150-159, 160-169 and ≥170 mm Hg, the odds ratios (95% confidence interval) for incident AF were 1.99 (1.10, 3.62), 1.19 (0.78, 1.81), 1.40 (0.93, 2.09), 2.02 (1.30, 3.15), 2.27 (1.31, 3.93) and 1.84 (0.89, 3.80), respectively. Based on the population attributable fraction (PAF), we estimated that, among patients with treated hypertension, 17.2% (95% CI 4.3%, 28.3%) of incident AF was attributable to an average achieved SBP ≥140 mmHg.
Among patients treated for hypertension, uncontrolled elevated SBP and SBP <120 mm Hg were associated with an increased risk of incident AF.
We investigated the risk of PD associated with calcium channel blockers (CCBs) and β-blockers in a population-based case-control study of 206 men and women between ages 35 and 89 with a new diagnosis of idiopathic PD between 1992 and 2002, and 383 controls without PD or other neurodegenerative disorders who were frequency matched on age, sex, duration of GHC enrollment and clinic. The adjusted odds ratio associated with ever use was 0.85 (95% confidence interval [CI]: 0.43, 1.66) for CCBs, and 1.20 (95% CI: 0.71, 2.03) for β-blockers. We observed no association with PD risk for either class of medication in terms of duration, dose, number of prescriptions or pattern of use. The weakness of these associations and the absence of additional influence of dose or duration of use argue against any causal interpretation.
Parkinson’s disease; Calcium Channel Blockers; β-blockers; Epidemiology; Case-Control
Gait variability is an index of how much gait parameters, such as step length, change from one step to the next. Gait variability increases with age and in individuals affected by cortical and subcortical neurodegenerative conditions, and it is associated with falls and incident mobility disability. The brain anatomical correlates of gait variability have not been studied in high-functioning community-dwelling older adults.
Gait variability and brain MRIs were assessed in a cohort of 331 men and women (mean age = 78.3 years) free from stroke, dementia or Parkinson's disease. Gait variability was computed for spatial parameters (step length and step width) and for temporal parameters (stance time). Subclinical brain vascular abnormalities were measured on brain MRIs as infarcts and white matter hyperintensities.
Greater variability of step length was associated with greater prevalence of infarcts, including infarcts in the basal ganglia, and with greater white matter hyperintensities severity, independent of age, gender, cognitive function and cardiovascular disease. Weaker associations were found between the other variability measures and the MRI measures.
In this group of older adults free from neurodegenerative diseases, a greater variability of step length was associated with greater burden of subclinical brain vascular abnormalities as defined by MRI.
Gait variability; White matter grade; Brain infarcts; Community-dwelling older adults
Genome-wide association studies (GWAS) have not consistently detected replicable genetic risk factors for ischemic stroke, potentially due to etiological heterogeneity of this trait. We performed GWAS of ischemic stroke and a major ischemic stroke subtype (large artery atherosclerosis, LAA) using 1,162 ischemic stroke cases (including 421 LAA cases) and 1,244 population controls from Australia. Evidence for a genetic influence on ischemic stroke risk was detected, but this influence was higher and more significant for the LAA subtype. We identified a new LAA susceptibility locus on chromosome 6p21.1 (rs556621: odds ratio (OR) = 1.62, P = 3.9 × 10−8) and replicated this association in 1,715 LAA cases and 52,695 population controls from 10 independent population cohorts (meta-analysis replication OR = 1.15, P = 3.9 × 10−4; discovery and replication combined OR = 1.21, P = 4.7 × 10−8). This study identifies a genetic risk locus for LAA and shows how analyzing etiological subtypes may better identify genetic risk alleles for ischemic stroke.
Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS).
From the CHS we selected 740 cognitively normal controls with a 1.5 T MRI scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software.
WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores.
Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function.
White matter lesions; age; gray matter volume; cognition
To determine whether the burden of leukoaraiosis and the number of brain infarcts, defined by MRI, are prospectively and independently associated with intraparenchymal hemorrhage (IPH) incidence in a pooled population-based study.
Among 4,872 participants initially free of clinical stroke in the Atherosclerosis Risk in Communities (ARIC) Study and the Cardiovascular Health Study (CHS), we assessed white matter grade (range 0–9), reflecting increasing leukoaraiosis, and brain infarcts using MRI. Over a median of 13 years of follow-up, 71 incident, spontaneous IPH events occurred.
After adjustment for other IPH risk factors, the hazard ratios (95% confidence intervals) across white matter grades 0–1, 2, 3, and 4–9 were 1.00, 1.68 (0.86–3.30), 3.52 (1.80–6.89), and 3.96 (1.90–8.27) (p for trend <0.0001). These hazard ratios were weakened only modestly (p for trend = 0.0003) with adjustment for MRI-defined brain infarcts. The IPH hazard ratios for 0, 1, 2, or ≥3 MRI-defined brain infarcts were 1.00, 1.97 (1.10–3.54), 2.00 (0.83–4.78), and 3.12 (1.31–7.43) (p for trend = 0.002), but these were substantially attenuated when adjusted for white matter grade (p for trend = 0.049).
Greater MRI-defined burden of leukoaraiosis is a risk factor for spontaneous IPH. Spontaneous IPH should be added to the growing list of potential poor outcomes in people with leukoaraiosis.