@article {1438, title = {Magnetic resonance abnormalities and cardiovascular disease in older adults. The Cardiovascular Health Study.}, journal = {Stroke}, volume = {25}, year = {1994}, month = {1994 Feb}, pages = {318-27}, abstract = {

BACKGROUND AND PURPOSE: Cerebral magnetic resonance imaging often detects abnormalities whose significance is unknown. The prevalence and correlates of findings such as ventricular enlargement, sulcal widening, and increased white matter signal intensity were examined in 303 men and women aged 65 to 95 years participating in a multicenter study of cardiovascular disease.

METHODS: Cerebral magnetic resonance imaging was performed and interpreted according to a standard protocol, and findings were correlated with measures of cardiovascular disease and its risk factors.

RESULTS: Measures of cerebral atrophy increased with age and were greater in men than in women (each P < .01). Ventricular enlargement and sulcal widening were associated with prior stroke, hypertension, diabetes, and white race (each P < .03). Extent of white matter hyperintensity was associated with age, prior stroke, hypertension, and use of diuretics (each P < .004). On multivariate analysis, age, male gender, white race, and prior stroke retained strong associations with increased ventricular and sulcal scores. After adjustment for age, prior stroke, and other risk factors, white matter hyperintensity was associated with atherosclerosis as measured by increased internal carotid artery thickness on ultrasound.

CONCLUSIONS: Cerebral atrophy and white matter hyperintensity are common in the elderly and are associated with age, prior stroke, and known cardiovascular risk factors. Though these findings have been suggested to represent normal aging, their wide variability and associations with cardiovascular disease argue against their inevitability with advancing age and support the need to identify modifiable risk factors for these abnormalities.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Analysis of Variance, Atrophy, Brain, Cerebral Ventricles, Cerebrovascular Disorders, Female, Humans, Magnetic Resonance Imaging, Male, Regression Analysis, Risk Factors, Sex Factors}, issn = {0039-2499}, author = {Manolio, T A and Kronmal, R A and Burke, G L and Poirier, V and O{\textquoteright}Leary, D H and Gardin, J M and Fried, L P and Steinberg, E P and Bryan, R N} } @article {1420, title = {A method for using MR to evaluate the effects of cardiovascular disease on the brain: the cardiovascular health study.}, journal = {AJNR Am J Neuroradiol}, volume = {15}, year = {1994}, month = {1994 Oct}, pages = {1625-33}, abstract = {

PURPOSE: To do a pilot study for the Cardiovascular Health Study (a population-based, longitudinal study of coronary heart disease and stroke in adults 65 years of age and older designed to identify risk factors related to cerebrovascular disease, particularly stroke): (a) to determine the feasibility of adding brain MR to the full-scale study; (b) to evaluate the reliability of standardized MR image interpretation in a multicenter study; and (c) to compare the prevalence of stroke determined by MR with that by clinical history.

METHODS: Protocol-defined MR studies were performed in 100 subjects with clinical histories of stroke and 203 subjects without reported histories of stroke. MR scans were independently evaluated by two trained neuroradiologists for the presence of small (< or = 3 mm) and large (> 3 mm) "infarctlike" lesions. The sizes of the cerebral sulci and lateral ventricles and the extent of white matter disease were graded on a scale of 0 to 9.

RESULTS: Eighty percent of the Cardiovascular Health Study participants who were invited to undergo MR studies agreed to do so; 95\% of those agreeing to the procedure successfully completed the exams. Intrareader and interreader reliability of infarctlike lesion identification was high for large lesions (kappa, 0.71 and 0.78, respectively) but not for small lesions (kappa, 0.71 and 0.32, respectively). Relaxed intrareader and interreader kappa scores for sulcal and ventricular sizes and extent of white matter disease were greater than 0.8 MR evidence of infarctlike lesions was present in 77\% of the participants with histories of stroke but was also present in 23\% of the participants without clinical histories of stroke. Seventy-nine percent of the infarctlike lesions were larger than 3 mm.

CONCLUSIONS: This preliminary study indicates that a large, prospective, epidemiologic study of elderly subjects using MR scans of the brain for identification of cerebrovascular disease is feasible and that the interpretative results are reproducible, and suggests that MR evidence of stroke is more prevalent than reported clinical history of stroke.

}, keywords = {Aged, Brain, Cerebral Infarction, Cerebral Ventricles, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Cross-Sectional Studies, Diagnosis, Differential, Feasibility Studies, Female, Humans, Image Interpretation, Computer-Assisted, Incidence, Longitudinal Studies, Magnetic Resonance Imaging, Male, Mass Screening, Observer Variation, Pilot Projects, Prospective Studies, Risk Factors, United States}, issn = {0195-6108}, author = {Bryan, R N and Manolio, T A and Schertz, L D and Jungreis, C and Poirier, V C and Elster, A D and Kronmal, R A} } @article {1471, title = {Infarctlike lesions in the brain: prevalence and anatomic characteristics at MR imaging of the elderly--data from the Cardiovascular Health Study.}, journal = {Radiology}, volume = {202}, year = {1997}, month = {1997 Jan}, pages = {47-54}, abstract = {

PURPOSE: To determine the prevalence and anatomic characteristics of infarctlike lesions seen on cranial magnetic resonance (MR) images.

MATERIALS AND METHODS: The study cohort consisted of 5,888 community-living individuals aged 65 years and older enrolled in a longitudinal, population-based study of cardiovascular disease. MR images were obtained from 3,658 participants and evaluated by trained readers. Lesion size, anatomic location, and signal intensity were recorded. Infarctlike lesion was defined as a nonmass, hyperintense region on spin-density- and T2-weighted images and, in cerebral white matter and brain stem, a hypointense region on T1-weighted images.

RESULTS: Infarctlike lesions were depicted on MR images of 1,323 (36\%) participants. Eighty-five percent (1,128 participants) had lesions 3 mm or larger in maximum dimension, although 70.9\% (1,320 of 1,861) of these lesions were 10 mm or less. Lesion prevalence increased with age, especially with lesions 3 mm or larger, which increased from 22.1\% (86 of 389) in the 65-69-year age group to 42.9\% (88 of 205) in the over-85-year age group (P < .0001). Lesion prevalence was slightly greater in men (497 of 1,527 [32.5\%]) than in women (631 of 2,131 [29.6\%]), but did not differ between blacks and non-blacks. The deep nuclei were the most commonly affected anatomic sites, with 78.2\% (1,451 of 1,856) of lesions. Lesions that involved the cerebrum and posterior fossa accounted for 11.7\% (218 of 1,856) and 10.1\% (187 of 1,856) of lesions, respectively.

CONCLUSION: If the lesions reported in this study indicate cerebrovascular disease, subclinical disease may be more prevalent than clinical disease, and the prevalence of disease may rise with age. Also, infarctlike lesions have a distinctive anatomic profile.

}, keywords = {Aged, Brain, Cardiovascular Diseases, Cerebral Infarction, Cohort Studies, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Prevalence}, issn = {0033-8419}, doi = {10.1148/radiology.202.1.8988191}, author = {Bryan, R N and Wells, S W and Miller, T J and Elster, A D and Jungreis, C A and Poirier, V C and Lind, B K and Manolio, T A} } @article {1469, title = {Sulcal, ventricular, and white matter changes at MR imaging in the aging brain: data from the cardiovascular health study.}, journal = {Radiology}, volume = {202}, year = {1997}, month = {1997 Jan}, pages = {33-9}, abstract = {

PURPOSE: To determine the distribution of changes in sulcal size, ventricular size, and white matter signal intensity depicted on cranial magnetic resonance (MR) images, with stratification according to age, race, and sex.

MATERIALS AND METHODS: Ventricular size, sulcal size, and white matter signal intensity changes were graded on cranial MR images of 3,660 community-living, elderly participants in the Cardiovascular Health Study. A healthier subgroup was also defined. Summary statistics for both groups were generated for age, race, and sex.

RESULTS: Regression models of the entire imaged cohort showed higher grades of all variables with increasing age, and higher ventricular and sulcal grades in men and in nonblack individuals. White matter grade was greater in women and in black individuals. Regression models of the healthier subgroup showed similar associations, except for a lack of association of sulcal and ventricular size with race.

CONCLUSION: Sulcal width, ventricular size, and white matter signal intensity change with age, sex, and race. Knowledge of these changes is important in appropriate interpretation of MR images of the elderly.

}, keywords = {Aged, Aged, 80 and over, Aging, Brain, Cardiovascular Diseases, Cerebral Ventricles, Cohort Studies, Continental Population Groups, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Reproducibility of Results, Sex Factors}, issn = {0033-8419}, doi = {10.1148/radiology.202.1.8988189}, author = {Yue, N C and Arnold, A M and Longstreth, W T and Elster, A D and Jungreis, C A and O{\textquoteright}Leary, D H and Poirier, V C and Bryan, R N} } @article {1519, title = {A brain image database for structure/function analysis.}, journal = {AJNR Am J Neuroradiol}, volume = {19}, year = {1998}, month = {1998 Nov-Dec}, pages = {1869-77}, abstract = {

BACKGROUND AND PURPOSE: Lesion-deficit-based structure-function analysis has traditionally been empirical and nonquantitative. Our purpose was to establish a new brain image database (BRAID) that allows the statistical correlation of brain functional measures with anatomic lesions revealed by clinical brain images.

METHODS: Data on 303 participants in the MR Feasibility Study of the Cardiovascular Health Study were tested for lesion/deficit correlations. Functional data were derived from a limited neurologic examination performed at the time of the MR examination. Image data included 3D lesion descriptions derived from the MR examinations by hand segmentation. MR images were normalized in-plane using local, linear Talairach normalization. A database was implemented to support spatial data structures and associated geometric and statistical operations. The database stored the segmented lesions, patient functional scores, and several anatomic atlases. Lesion-deficit association was sought by contingency testing (chi2-test) for every possible combination of each neurologic variable and each labeled atlas structure. Significant associations that confirmed accepted lesion-deficit relationships were sought.

RESULTS: Two-hundred thirty-five infarctlike lesions in 117 subjects were viewed collectively after mapping into Talairach cartesian coordinates. Anatomic structures most strongly correlated with neurologic deficits tended to be situated in anatomically appropriate areas. For example, infarctlike lesions associated with visual field defects were correlated with structures in contralateral occipital structures, including the optic radiations and occipital gyri.

CONCLUSION: Known lesion-deficit correlations can be established by a database using a standard coordinate system for representing spatial data and incorporating functional and structural data together with appropriate query mechanisms. Improvements and further applications of this methodology may provide a powerful technique for uncovering new structure-function relationships.

}, keywords = {Brain, Brain Mapping, Cerebral Infarction, Databases as Topic, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Neurologic Examination}, issn = {0195-6108}, author = {Letovsky, S I and Whitehead, S H and Paik, C H and Miller, G A and Gerber, J and Herskovits, E H and Fulton, T K and Bryan, R N} } @article {1495, title = {Sex differences in brain aging: a quantitative magnetic resonance imaging study.}, journal = {Arch Neurol}, volume = {55}, year = {1998}, month = {1998 Feb}, pages = {169-79}, abstract = {

BACKGROUND: Little is known about the effect of sex on age-related changes in brain structure.

METHODS: Quantitative magnetic resonance imaging of the brain was performed in 330 elderly (age range, 66-96 years) volunteers living independently in the community, all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images by means of computer-assisted edge detection and trace methods. High measurement reliabilities were obtained.

RESULTS: Age-specific changes in brain size were significantly greater in men than women for the peripheral (sulcal) cerebrospinal fluid volume, the lateral (sylvian) fissure cerebrospinal fluid volume, and the parieto-occipital region area. Main effects of age were observed for all the remaining brain regions examined (cerebral hemisphere volume, frontal region area, temporoparietal region area, lateral ventricular volume, and third ventricle volume), but these effects were similar in men and women. Asymmetries in brain structures were not affected by aging in either sex.

CONCLUSIONS: Our results are generally consistent with the few published studies on sex differences in brain aging and suggest that, for at least some structures, aging effects may be more apparent in men than women. The neurobiological bases and functional correlates of these sex differences require further investigation.

}, keywords = {Age Distribution, Aged, Aged, 80 and over, Aging, Atrophy, Brain, Cerebrospinal Fluid, Diagnosis, Computer-Assisted, Female, Health Status, Humans, Magnetic Resonance Imaging, Male, Regression Analysis, Sex Characteristics, Sex Distribution}, issn = {0003-9942}, author = {Coffey, C E and Lucke, J F and Saxton, J A and Ratcliff, G and Unitas, L J and Billig, B and Bryan, R N} } @article {604, title = {Neuroanatomic and functional correlates of depressed mood: the Cardiovascular Health Study.}, journal = {Am J Epidemiol}, volume = {150}, year = {1999}, month = {1999 Nov 01}, pages = {919-29}, abstract = {

Although a number of studies suggest an association between stroke and depression, few have examined the relation between magnetic resonance imaging (MRI)-identified lesions and depression among community-dwelling older adults. This cross-sectional study sought to assess the association between MRI infarcts in the basal ganglia and non-basal-ganglia areas, potential functional consequences of these lesions, and depressive symptomatology in 3,371 US men and women aged 65 years or older who participated in the Cardiovascular Health Study between 1992 and 1994. By using multiple linear regression models, the authors found that after adjustment for age, gender, and stroke history, Center for Epidemiologic Studies Depression Scale scores were independently associated with non-basal-ganglia lesions (p = 0.04) but were not independently associated with basal ganglia lesions (p = 0.11). When measures of physical disability and cognitive impairment were added to the models, these measures displaced MRI-identified infarcts in their association with depressive symptoms. In additional models, hemispheric location and size of the basal ganglia lesion were found to have no relation to depression levels. These results suggest that the functional consequences of cerebrovascular disease may be the causal pathway by which basal ganglia and non-basal-ganglia lesions are associated with depressive symptomatology.

}, keywords = {Activities of Daily Living, Aged, Aged, 80 and over, Basal Ganglia, Cerebral Infarction, Cognition, Cross-Sectional Studies, Depression, Female, Geriatric Assessment, Humans, Linear Models, Magnetic Resonance Imaging, Male, Psychiatric Status Rating Scales, Risk Factors, United States}, issn = {0002-9262}, doi = {10.1093/oxfordjournals.aje.a010100}, author = {Sato, R and Bryan, R N and Fried, L P} } @article {598, title = {Relation of education to brain size in normal aging: implications for the reserve hypothesis.}, journal = {Neurology}, volume = {53}, year = {1999}, month = {1999 Jul 13}, pages = {189-96}, abstract = {

OBJECTIVE: To examine the relations between education and age-related changes in brain structure in a nonclinical sample of elderly adults.

BACKGROUND: Education may protect against cognitive decline in late life--an observation that has led to the "reserve" hypothesis of brain aging. Little is known, however, about the effect of education on age-related changes in brain structure.

METHODS: Quantitative MRI of the brain was performed in 320 elderly volunteers (age range, 66 to 90 years) living independently in the community (Mini-Mental State Examination scores > or =24), all of whom were participants in the Cardiovascular Health Study. Blinded measurements of global and regional brain size were made from T1-weighted axial images using computer-assisted edge detection and trace methodology. High measurement reliabilities were obtained.

RESULTS: Regression analyses (adjusting for the effects of intracranial size, sex, age, age-by-sex interactions, and potential confounders) revealed significant main effects of education on peripheral (sulcal) CSF volume-a marker of cortical atrophy. Each year of education was associated with an increase in peripheral CSF volume of 1.77 mL (p<0.03). As reported previously, main effects of age (but not education) were observed for all of the remaining brain regions examined, including cerebral hemisphere volume, frontal region area, temporoparietal region area, parieto-occipital region area, lateral (Sylvian) fissure volume, lateral ventricular volume, and third ventricle volume.

CONCLUSIONS: The authors{\textquoteright} findings demonstrate a relation between education and age-related cortical atrophy in a nonclinical sample of elderly persons, and are consistent with the reserve hypothesis as well as with a small number of brain imaging studies in patients with dementia. The neurobiological basis and functional correlates of this education effect require additional investigation.

}, keywords = {Aged, Aged, 80 and over, Atrophy, Brain, Cerebral Cortex, Cerebrospinal Fluid, Educational Status, Female, Functional Laterality, Health Status, Humans, Magnetic Resonance Imaging, Male, Mental Status Schedule, Regression Analysis, Sex Characteristics}, issn = {0028-3878}, doi = {10.1212/wnl.53.1.189}, author = {Coffey, C E and Saxton, J A and Ratcliff, G and Bryan, R N and Lucke, J F} } @article {647, title = {Association between blood pressure level and the risk of myocardial infarction, stroke, and total mortality: the cardiovascular health study.}, journal = {Arch Intern Med}, volume = {161}, year = {2001}, month = {2001 May 14}, pages = {1183-92}, abstract = {

BACKGROUND: Recent reports have drawn attention to the importance of pulse pressure as a predictor of cardiovascular events. Pulse pressure is used neither by clinicians nor by guidelines to define treatable levels of blood pressure.

METHODS: In the Cardiovascular Health Study, 5888 adults 65 years and older were recruited from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination, and all subsequent cardiovascular events were ascertained and classified.

RESULTS: At baseline, 1961 men and 2941 women were at risk for an incident myocardial infarction or stroke. During follow-up that averaged 6.7 years, 572 subjects had a coronary event, 385 had a stroke, and 896 died. After adjustment for potential confounders, systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse pressure were directly associated with the risk of incident myocardial infarction and stroke. Only SBP was associated with total mortality. Importantly, SBP was a better predictor of cardiovascular events than DBP or pulse pressure. In the adjusted model for myocardial infarction, a 1-SD change in SBP, DBP, and pulse pressure was associated with hazard ratios (95\% confidence intervals) of 1.24 (1.15-1.35), 1.13 (1.04-1.22), and 1.21 (1.12-1.31), respectively; and adding pulse pressure or DBP to the model did not improve the fit. For stroke, the hazard ratios (95\% confidence intervals) were 1.34 (1.21-1.47) with SBP, 1.29 (1.17-1.42) with DBP, and 1.21 (1.10-1.34) with pulse pressure. The association between blood pressure level and cardiovascular disease risk was generally linear; specifically, there was no evidence of a J-shaped relationship. In those with treated hypertension, the hazard ratios for the association of SBP with the risks for myocardial infarction and stroke were less pronounced than in those without treated hypertension.

CONCLUSION: In this population-based study of older adults, although all measures of blood pressure were strongly and directly related to the risk of coronary and cerebrovascular events, SBP was the best single predictor of cardiovascular events.

}, keywords = {Aged, Blood Pressure, Female, Humans, Male, Myocardial Infarction, Prognosis, Proportional Hazards Models, Prospective Studies, Risk Factors, Stroke, Survival Rate, United States}, issn = {0003-9926}, doi = {10.1001/archinte.161.9.1183}, author = {Psaty, B M and Furberg, C D and Kuller, L H and Cushman, M and Savage, P J and Levine, D and O{\textquoteright}Leary, D H and Bryan, R N and Anderson, M and Lumley, T} }