Patterns on cranial magnetic resonance imaging in elderly people and vascular disease outcomes.
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Aged↗
Biomedical subjects
W T Longstreth
Publications and source records attributed to W T Longstreth.
Cluster analysis and patterns of findings on cranial magnetic resonance imaging of the elderly: the Cardiovascular Health Study.
OBJECTIVE: To characterize patterns of findings on cranial magnetic resonance imaging (MRI) of the elderly using a statistical technique called cluster analysis. SUBJECTS AND METHODS: The Cardiovascular Health Study is a population-based, longitudinal study of 5888 people 65 years and older. Of these, 3230 underwent cranial MRI scans, which were coded for presence of infarcts and grades for white matter, ventricles, and sulci. Cluster analysis separated participants into 5 clusters based solely on patterns of MRI findings. Participants comprising each cluster were contrasted with respect to cardiovascular risk factors and clinical manifestations. RESULTS: One cluster was low on all the MRI findings (normal) and another was high on all of them (complex infarcts). Another cluster had evidence for infarcts alone (simple infarcts), whereas the last 2 clusters lacked infarcts, one having enlarged ventricles and sulci (atrophy) and the other having prominent white matter changes and enlarged ventricles (leukoaraiosis). Factors that distinguished these clusters in a discriminant analysis were age, sex, several measures of hypertension, internal carotid artery wall thickness, smoking, and prevalent claudication before the MRI. The atrophy group had the highest percentage of men and the normal group had the lowest. Cognitive and motor performance also differed across clusters, with the atrophy cluster performing better than may have been expected. CONCLUSIONS: These MRI patterns identified participants with different vascular disease risk factors and clinical manifestations. Results of these exploratory analyses warrant consideration in other populations of elderly people. Such patterns may provide clues about the pathophysiology of structural brain changes in the elderly.
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Genetic polymorphisms of microsomal and soluble epoxide hydrolase and the risk of Parkinson's disease.
Oxidative stress is hypothesized to play a major role in the destruction of dopaminergic neurons, which is associated with Parkinson's disease. Epoxides are potentially reactive intermediates formed through the oxidative metabolism of both exogenous and endogenous substances that contribute to cytotoxic damage mediated by oxidative stress. The microsomal (EPHX1) and soluble (EPHX2) epoxide hydrolases function to regulate the oxidation status of a wide range of xenobiotic- and lipid-derived substrates; therefore, interindividual variation in these pathways may mitigate epoxide-related cellular injury. In this investigation, we examined the potential association between the risk of Parkinson's disease and genetic variation within the EPHX1 and EPHX2 genes. Fluorescent 5' nuclease-based assays were developed to identify the allelic status of individuals with respect to specific single nucleotide polymorphisms in exons 3 and 4 of the EPHX1 gene and exons 8 and 13 of the EPHX2 gene. EPHX1 and EPHX2 genotype data were obtained from 133 idiopathic Parkinson's disease patients and 212 control subjects matched on age, gender and ethnicity. No statistically significant differences were found in the distribution of the reference and variant alleles between Parkinson's disease and control subjects, or when results were stratified by gender. Therefore, common polymorphisms within EPHX1 and EPHX2 do not appear to be important risk factors for Parkinson's disease.
Adult↗
Parkinsonism and occupational exposure to pesticides.
OBJECTIVE: To examine the risk of parkinsonism related to lifetime occupational exposure to pesticides among a cohort of men, mostly orchardists, in Washington State. METHODS: All 310 subjects in this study had previously participated in a cohort study of men occupationally exposed to pesticides. Subjects were given a structured neurological examination and completed a self administered questionnaire which elicited detailed information on pesticide (insecticide, herbicide, and fungicide) use throughout their working careers. Demographic characteristics were also sought. Subjects had a mean age of 69.6 years (range 49-96, SD 8.1). There were 238 (76.8%) subjects who reported some occupational exposure to pesticides, whereas 72 (23.2%) reported none. Parkinsonism was defined by the presence of two or more of rest tremor, rigidity, bradykinesia, and impairment of postural reflexes in subjects not on antiparkinsonian medication, or the presence of at least one sign if they were on such medication. Parkinson's disease was not studied explicitly because of the difficulty in distinguishing it from other parkinsonian syndromes. A generalised linear model was used to estimate prevalence ratios (PRs) for parkinsonism relative to history of farming, pesticide use, and use of well water. RESULTS: A PR of 2.0 (95% confidence interval (95% CI) 1.0 to 4.2) was found for subjects in the highest tertile of years of exposure to pesticides; a similarly increased, non-significant, PR was found for the middle tertile (1.9 (95% CI 0.9 to 4.0)), although a trend test did not show a significant exposure-response relation. No increased risks were found associated with specific pesticides or pesticide classes, nor with a history of farming or use of well water. CONCLUSION: Parkinsonism may be associated with long term occupational exposure to pesticides, although no associations with specific pesticides could be detected. This finding is consistent with most of the publications on this topic.
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Longitudinal study of blood pressure and stroke in over 37,000 People in China.
As part of a longitudinal study performed in urban China, 37,655 subjects were evaluated for stroke risk factors, including having their blood pressure measured in a standard fashion. The cohort was followed for 3.5 years during which time 427 subjects experienced incident strokes--221 ischemic, 203 hemorrhagic, and 3 undefined. Both systolic and diastolic blood pressure were significantly related to risk of stroke and stroke type. Associations were stronger for systolic than diastolic blood pressure. These results emphasize the importance of systolic blood pressure, as opposed to diastolic, as a risk factor for stroke. In this study, the risk of stroke is increased by about 25% with each 10 mm Hg increase in systolic blood pressure.
Adult↗
Alcohol consumption and subclinical findings on magnetic resonance imaging of the brain in older adults: the cardiovascular health study.
BACKGROUND AND PURPOSE: Subclinical findings on MRI of the brain are associated with poorer cognitive and neurological function among older adults. We sought to determine how alcohol consumption is related to these findings. METHODS: As part of the Cardiovascular Health Study, 3660 adults aged 65 years and older underwent MRI of the brain from 1992 to 1994. We excluded 284 participants with a confirmed history of cerebrovascular disease. We assessed self-reported intake of beer, wine, and liquor at the annual clinic visit closest to the date of the MRI and grouped participants into 6 categories: abstainers, former drinkers, <1 drink weekly, 1 to <7 drinks weekly, 7 to <15 drinks weekly, and >/=15 drinks weekly. Neuroradiologists assessed white matter grade, infarcts, ventricular size, and sulcal size in a standardized and blinded manner. We used multivariate regression to control for sociodemographic and clinical characteristics. RESULTS: We found a U-shaped relationship between alcohol consumption and white matter abnormalities. Compared with abstainers, individuals consuming 1 to <7 drinks had an OR of 0.68, and those consuming >/=15 drinks weekly had an OR of 0.95 (p for quadratic term=0.01). Heavier alcohol consumption was associated with a lower prevalence of infarcts (OR for >/=15 drinks weekly relative to abstainers 0.59; P for trend=0.004), but larger ventricular size (OR for >/=15 drinks weekly relative to abstainers 1.32; P for trend=0.006) and sulcal size (OR for >/=15 drinks weekly relative to abstainers 1.53; P for trend=0.007). CONCLUSIONS: Moderate alcohol consumption is associated with a lower prevalence of white matter abnormalities and infarcts, thought to be of vascular origin, but with a dose-dependent higher prevalence of brain atrophy on MRI among older adults. The extent to which these competing associations influence overall brain function will require further study.
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Polymorphisms of coagulation factor XIII subunit A and risk of nonfatal hemorrhagic stroke in young white women.
BACKGROUND AND PURPOSE: Although family studies have suggested a genetic influence on hemorrhagic stroke, the underlying genetic risk factors remain poorly defined. Coagulation factor XIII, which is involved in hemostasis, fibrinolysis, vascular remodeling, and tissue repair, represents a candidate gene for hemorrhagic stroke. We assessed the potential role of 3 factor XIII subunit A coding-sequence polymorphisms, along with a promoter polymorphism of plasminogen activator inhibitor-1 (PAI-1, which is also involved in fibrin stabilization and vascular remodeling), in young white women with hemorrhagic stroke. METHODS: Genotype analysis for factor XIII subunit A Val34Leu, Tyr204Phe, and Pro564Leu and for PAI-1 -675 4G/5G was performed in a population-based case-control study of 42 white women aged <45 years with nonfatal hemorrhagic stroke and 345 demographically similar control subjects. RESULTS: Compared with the respective homozygous wild-type genotypes, the Tyr204/Phe204 genotypes (age-adjusted odds ratio [OR] 2.9, 95% 95% CI 1.1 to 7.5) and the Leu564/Leu564 genotype (OR 4.3, 95% CI 1.4 to 13.7) were each associated with an increased risk of nonfatal hemorrhagic stroke. The risk estimate associated with the Phe204 variant was highest in women with subarachnoid hemorrhage and in nonsmokers, whereas the risk estimate of the Leu564/Leu564 genotype was highest in women with intracerebral hemorrhage and in smokers. Women who carried either the Phe204 allele or the Leu564/Leu564 genotype in combination with the PAI-1 5G/5G genotype had a nearly 20-fold increased risk of hemorrhagic stroke (OR 18.9, 95% CI 3.8 to 95.1). CONCLUSIONS: Our findings suggest that the Phe204 and Leu564 variants of coagulation factor XIII may be markers for genetic susceptibility to hemorrhagic stroke in women aged <45 years.
Adolescent↗
Aspirin in acute ischemic stroke.
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Ancrod↗
Alcohol consumption and the risk of stroke.
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Alcohol Drinking↗
Somatosensory potentials, CSF creatine kinase BB activity, and awakening after cardiac arrest.
OBJECTIVE: To examine the utility of somatosensory evoked potential (SEP) peaks and CSF creatine kinase BB isoenzyme activity (CKBB) in predicting nonawakening from coma due to cardiac arrest. BACKGROUND: Accurate predictors of neurologic outcome in patients comatose after cardiac arrest are needed to improve medical decision making. METHODS: A total of 72 comatose patients had bilateral median SEPs, and of these, 52 had CSF and CKBB. Awakening was defined as following commands or having comprehensible speech. Both short (N1) and long (N3) latency SEP peaks were analyzed. Nonparametric analyses were used. RESULTS: For patients who had both tests, CKBB > or = 205 U/L predicted nonawakening with a sensitivity of 49% and a specificity of 100%. Bilateral absence of the N1 peak predicted nonawakening with a sensitivity of 53% and a specificity of 100%. Using CKBB > or = 205 U/L, bilaterally absent SEP N1 peaks, or both predicted nonawakening with a sensitivity of 69% and a specificity of 100%. Using CKBB > or = 205 U/L, bilaterally absent N1 peaks, bilateral N3 > or = 176 msec or absent, or some combination predicted nonawakening with a sensitivity of 78% and a specificity of 100%. CONCLUSION: The combination of an absent N1 peak and elevated CKBB performs better than either alone in predicting nonawakening after cardiac arrest. Prolonged or absent N3 latency may increase sensitivity. These results should be interpreted with caution given the small number of patients and the possibility of a self-fulfilling prophecy.
Adolescent↗
Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. I. Cigarette smoking and alcohol consumption.
The associations of cigarette smoking and alcohol consumption with the risk of amyotrophic lateral sclerosis (ALS) were investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and were matched to population controls (n = 321) identified through random digit dialing and Medicare enrollment files. Conditional logistic regression analysis was used to compute odds ratios adjusted for age, gender, respondent type, and education. The authors found that alcohol consumption was not associated with the risk of ALS. Ever having smoked cigarettes was associated with a twofold increase in risk (alcohol-adjusted odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.2). A greater than threefold increased risk was observed for current smokers (alcohol-adjusted OR = 3.5, 95% CI: 1.9, 6.4), with only a modestly increased risk for former smokers (alcohol-adjusted OR = 1.5, 95% CI: 0.9, 2.4). Significant trends in the risk of ALS were observed with duration of smoking (p for trend = 0.001) and number of cigarette pack-years (p for trend = 0.001). The finding that cigarette smoking is a risk factor for ALS is consistent with current etiologic theories that implicate environmental chemicals and oxidative stress in the pathogenesis of ALS.
Adult↗
Population-based case-control study of amyotrophic lateral sclerosis in western Washington State. II. Diet.
The association of nutrient intake with the risk of amyotrophic lateral sclerosis (ALS) was investigated in a population-based case-control study conducted in three counties of western Washington State from 1990 to 1994. Incident ALS cases (n = 161) were identified and individually matched on age and gender to population controls (n = 321). A self-administered food frequency questionnaire was used to assess nutrient intake. Conditional logistic regression analysis was used to compute odds ratios adjusted for education, smoking, and total energy intake. The authors found that dietary fat intake was associated with an increased risk of ALS (highest vs. lowest quartile, fiber-adjusted odds ratio (OR) = 2.7, 95% confidence interval (CI): 0.9, 8.0; p for trend = 0.06), while dietary fiber intake was associated with a decreased risk of ALS (highest vs. lowest quartile, fat-adjusted OR = 0.3, 95% CI: 0.1, 0.7; p for trend = 0.02). Glutamate intake was associated with an increased risk of ALS (adjusted OR for highest vs. lowest quartile = 3.2, 95% CI: 1.2, 8.0; p for trend < 0.02). Consumption of antioxidant vitamins from diet or supplement sources did not alter the risk. The positive association with glutamate intake is consistent with the etiologic theory that implicates glutamate excitotoxicity in the pathogenesis of ALS, whereas the associations with fat and fiber intake warrant further study and biologic explanation.
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Physical activity and subarachnoid haemorrhage: a population based case-control study.
OBJECTIVE: To evaluate physical activity as a risk factor for subarachnoid haemorrhage. METHODS: A population based case-control study in King County, Washington. A standardised, personal interview was used to determine physical activity during the past year and at the onset of the bleed for case patients and a similar reference time for control subjects. Conditional logistic regression and a case cross over analysis were performed in which each case patient served as his or her own control. Subjects were 149 men and women with incident, spontaneous subarachnoid haemorrhage and two control subjects per case patient. Control subjects were identified through random digit dialing and matched on age, sex, and respondent type. RESULTS: Four of the 149 (2.7%) case patients were engaged in vigorous physical activity at the time of their subarachnoid haemorrhage. With those who were engaged in non-vigorous or no physical activity serving as the reference group, the relative risk of sustaining a subarachnoid haemorrhage for those engaged in vigorous physical activity was 11.6 (95% confidence interval (95% CI) 1.2-113.2). In the case cross over analysis, the relative risk was 15.0 (95% CI 4.3-52.2). Higher levels of long term regular physical activity over the past year were associated with a lower, but not statistically significant, risk of subarachnoid haemorrhage (test for trend, p=0.3). CONCLUSION: The risk of subarachnoid haemorrhage is increased during vigorous physical activity, although only a few result from this mechanism.
Adult↗
Control of blood pressure and risk of stroke among pharmacologically treated hypertensive patients.
BACKGROUND AND PURPOSE: Despite improved control of blood pressure during the last decades in the United States, a considerable proportion of treated hypertensives have not achieved target blood pressure levels. We estimated the proportion of strokes occurring among treated hypertensive patients that may be attributable to uncontrolled blood pressure. METHODS: A population-based case-control study was conducted among treated hypertensive members of Group Health Cooperative of Puget Sound. Cases were treated hypertensive patients who sustained a first fatal or nonfatal, ischemic (n=460) or hemorrhagic (n=95) stroke during 1989-1996. Controls were a random sample of stroke-free, treated hypertensive Group Health Cooperative enrollees (n=2966), similar in age to the stroke cases. Multiple measurements of blood pressure and other cardiovascular risk factors were collected from medical records. Logistic regression was used to estimate the risk of ischemic stroke and hemorrhagic stroke associated with uncontrolled blood pressure, defined as diastolic blood pressure >90 mm Hg or systolic blood pressure >140 mm Hg. The fraction of strokes attributable to uncontrolled blood pressure among treated hypertensives was calculated. RESULTS: Blood pressure was uncontrolled in 78% of ischemic stroke cases, 85% of hemorrhagic stroke cases, and 65% of controls. After adjustment for potential confounders, uncontrolled blood pressure among treated hypertensive patients was moderately associated with ischemic stroke (risk ratio=1.5 [95% CI, 1.2 to 1. 9]) and strongly related to hemorrhagic stroke (risk ratio=3.0 [95% CI, 1.7 to 5.4]). We estimated that 27% (95% CI, 11% to 39%) of the ischemic strokes and 57% (95% CI, 26% to 75%) of the hemorrhagic strokes among treated hypertensive patients were attributable to uncontrolled blood pressure. Overall, 32% (95% CI, 14% to 45%) of all strokes were attributable to uncontrolled blood pressure. CONCLUSIONS: A considerable proportion of incident strokes among treated hypertensive patients may be prevented by achieving control of blood pressure.
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Cerebral venous thrombosis and the G20210A mutation of factor II.
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Adult↗
Genetic variants of platelet glycoprotein receptors and risk of stroke in young women.
BACKGROUND AND PURPOSE: A number of studies have examined the relationship between genetic platelet glycoprotein variants and early-onset atherothrombotic disease, particularly acute myocardial infarction. Data on the association of these genetic susceptibility markers with ischemic stroke are more limited, and their role in hemorrhagic stroke has not been previously examined. METHODS: We performed genotype analysis for 5 common diallelic platelet glycoprotein polymorphisms in a population-based study of 78 white women aged <45 years with arterial stroke (36 ischemic cases and 42 hemorrhagic cases) and 346 demographically similar control subjects. RESULTS: The 807T variant of glycoprotein Ia was associated with a 2-fold increased risk of ischemic stroke (age-adjusted odds ratio [OR]=2.24; 95% CI=0.99 to 5.06). The Met(145) allele of glycoprotein Ibalpha was associated with a trend toward an increased risk of ischemic stroke that was more pronounced in the homozygous state (OR=10.36), but the CI is extremely wide because of the small numbers of subjects (95% CI=1.43 to 79.34). Homozygosity for the Ser(843) allele of the glycoprotein IIb was associated with an approximately 5-fold increased risk of ischemic stroke among subgroups of women who carried a diagnosis of hypertension or diabetes (OR=4.51; 95% CI=1.01 to 20.13) or had elevated plasma homocysteine levels (OR=5.94; 95% CI=1.53 to 23.05). The genotype distributions for all 5 platelet glycoprotein polymorphisms were similar among hemorrhagic stroke cases and controls. CONCLUSIONS: Several inherited platelet glycoprotein variants may be associated with an increased risk of ischemic stroke in young women. These associations seemed to be confined to women with other cardiovascular risk factors. Additional studies involving larger numbers of subjects are needed to confirm these preliminary findings.
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Quantitative assessment of subclinical spasticity in human T-cell lymphotropic virus type I infection.
OBJECTIVE: To compare human T-cell lymphotrophic virus type I (HTLV-I) seropositive and seronegative women for symptoms and signs of spasticity. BACKGROUND: 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. METHODS: 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. 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. CONCLUSIONS: 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.
Adult↗
Cerebral hypoxia after cardiopulmonary resuscitation.
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Cardiopulmonary Resuscitation↗