@article {1491, title = {The association of antihypertensive agents with MRI white matter findings and with Modified Mini-Mental State Examination in older adults.}, journal = {J Am Geriatr Soc}, volume = {45}, year = {1997}, month = {1997 Dec}, pages = {1423-33}, abstract = {

OBJECTIVES: To examine the association of antihypertensive regimen with magnetic resonance imaging (MRI) white matter hyperintensity and with cognitive impairment in older adults.

DESIGN: Cross-sectional study.

SETTING: The Cardiovascular Health study, an observational prospective cohort study of risk factors for coronary heart disease and stroke in men and women 65 years of age and older.

PARTICIPANTS: 1268 men and women with pharmacologically treated hypertension.

MEASUREMENTS: Information on medication use, medical history, and health habits was collected at clinic examinations. Participants completed the Modified Mini-Mental State Examination (3MS) and underwent MRI examination. Without clinical information, study neuroradiologists assigned an overall grade of white matter signal intensity on MRI on a scale from 0 (no findings) to 9 (extensive findings).

RESULTS: Adjusted mean white matter grade was higher for users of calcium channel blockers (2.59, P = .007) and users of loop diuretics (2.60, P = .015) than for users of beta blockers (2.12). The association was present for both dihydropyridine and non-dihydropyridine calcium channel blockers. Adjusted mean 3MS scores were lower for users of calcium channel blockers (89.6, P < .002), especially dihydropyridines, and users of loop diuretics (89.7, P < .006) than for users of beta blockers (92.3). No statistically significant association could be shown for users of other drug regimens, including thiazides and ACE inhibitors.

CONCLUSION: In this study, users of antihypertensive regimens which included calcium channel blockers or loop diuretics had more severe white matter hyperintensity on MRI and worse performance on 3MS than users of beta blockers.

}, keywords = {Adrenergic beta-Antagonists, Aged, Aged, 80 and over, Antihypertensive Agents, Brain, Calcium Channel Blockers, Cognition, Cohort Studies, Cross-Sectional Studies, Diuretics, Female, Geriatric Assessment, Humans, Magnetic Resonance Imaging, Male, Risk Factors}, issn = {0002-8614}, author = {Heckbert, S R and Longstreth, W T and Psaty, B M and Murros, K E and Smith, N L and Newman, A B and Williamson, J D and Bernick, C and Furberg, C D} } @article {1514, title = {Lacunar infarcts defined by magnetic resonance imaging of 3660 elderly people: the Cardiovascular Health Study.}, journal = {Arch Neurol}, volume = {55}, year = {1998}, month = {1998 Sep}, pages = {1217-25}, abstract = {

OBJECTIVE: To identify risk factors for and functional consequences of lacunar infarct in elderly people.

METHODS: The Cardiovascular Health Study (CHS) is a longitudinal study of people 65 years or older, in which 3660 participants underwent cranial magnetic resonance imaging (MRI). Neuroradiologists read scans in a standard fashion without any clinical information. Lacunes were defined as subcortical areas consistent with infarcts measuring 3 to 20 mm. In cross-sectional analyses, clinical correlates were contrasted among groups defined by MRI findings.

RESULTS: Of the 3660 subjects who underwent MRI, 2529 (69\%) were free of infarcts of any kind and 841 (23\%) had 1 or more lacunes without other types present, totaling 1270 lacunes. For most of these 841 subjects, their lacunes were single (66\%) and silent (89\%), namely without a history of transient ischemic attack or stroke. In multivariate analyses, factors independently associated with lacunes were increased age, diastolic blood pressure, creatinine, and pack-years of smoking (listed in descending order of strength of association; for all, P < .005), as well as maximum internal carotid artery stenosis of more than 50\% (odds ratio [OR], 1.81; P < .005), male sex (OR, 0.74; P < .005), and history of diabetes at entrance into the study (OR, 1.33; P < .05). Models for subgroups of single, multiple, silent, and symptomatic lacunes differed only minimally. Those with silent lacunes had more cognitive, upper extremity, and lower extremity dysfunction not recognized as stroke than those whose MRIs were free of infarcts.

CONCLUSIONS: In this group of older adults, lacunes defined by MRI are common and associated with factors that likely promote or reflect small-vessel disease. Silent lacunes are also associated with neurologic dysfunction.

}, keywords = {Aged, Cerebral Infarction, Female, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Multivariate Analysis, Risk Factors}, issn = {0003-9942}, author = {Longstreth, W T and Bernick, C and Manolio, T A and Bryan, N and Jungreis, C A and Price, T R} } @article {629, title = {Frequency and predictors of stroke death in 5,888 participants in the Cardiovascular Health Study.}, journal = {Neurology}, volume = {56}, year = {2001}, month = {2001 Feb 13}, pages = {368-75}, abstract = {

BACKGROUND: Few population-based studies have examined in detail issues of stroke-related deaths in elderly people.

METHODS: Participants in the Cardiovascular Health Study (CHS) are 65 years of age or older, have had extensive baseline evaluations, and have been followed-up for fatal and nonfatal cardiovascular and cerebrovascular disease outcomes. Investigators adjudicated these outcomes and classified strokes by types and subtypes.

RESULTS: Over 7 years, 1,310 (22.2\%) of 5,888 participants died, and 455 (7.7\%) experienced incident stroke. For the 5,888, stroke mortality was 3.2 per 1,000 person-years. For the 455, it was 36.1 per 1,000 person-years, with the most lethal type being hemorrhagic and the ischemic subtype being cardioembolic. After controlling for age and stroke type, the only other independent predictor of death after any stroke was poor performance on a timed walk measured before the incident stroke. Considering only ischemic stroke, the independent predictors of death were African American race and poor performance on timed walk.

CONCLUSION: In CHS, death attributable to stroke is common. As in other studies, the most lethal stroke type was hemorrhagic, and ischemic stroke subtype, cardioembolic. Slow walking, possibly a measure of frailty, was associated with an increased risk of death of stroke. Finally, African Americans faced a greater risk of death than others after an ischemic stroke.

}, keywords = {Aged, Aged, 80 and over, Clinical Trials as Topic, Female, Humans, Longitudinal Studies, Male, Predictive Value of Tests, Stroke, Survival Analysis, United States}, issn = {0028-3878}, doi = {10.1212/wnl.56.3.368}, author = {Longstreth, W T and Bernick, C and Fitzpatrick, A and Cushman, M and Knepper, L and Lima, J and Furberg, C D} } @article {663, title = {Silent MRI infarcts and the risk of future stroke: the cardiovascular health study.}, journal = {Neurology}, volume = {57}, year = {2001}, month = {2001 Oct 09}, pages = {1222-9}, abstract = {

BACKGROUND: Silent infarcts are commonly discovered on cranial MRI in the elderly.

OBJECTIVE: To examine the association between risk of stroke and presence of silent infarcts, alone and in combination with other stroke risk factors.

METHODS: Participants (3,324) in the Cardiovascular Health Study (CHS) without a history of stroke underwent cranial MRI scans between 1992 and 1994. Silent infarcts were defined as focal lesions greater than 3 mm that were hyperintense on T2 images and, if subcortical, hypointense on T1 images. Incident strokes were identified and classified over an average follow-up of 4 years. The authors evaluated the risk of subsequent symptomatic stroke and how it was modified by other potential stroke risk factors among those with silent infarcts.

RESULTS: Approximately 28\% of CHS participants had evidence of silent infarcts (n = 923). The incidence of stroke was 18.7 per 1,000 person-years in those with silent infarcts (n = 67) compared with 9.5 per 1,000 person-years in the absence of silent infarcts. The adjusted relative risk of incident stroke increased with multiple (more than one) silent infarcts (hazard ratio 1.9 [1.2 to 2.8]). Higher values of diastolic and systolic blood pressure, common and internal carotid wall thickness, and the presence of atrial fibrillation were associated with an increased risk of strokes in those with silent infarcts (n = 53 strokes).

CONCLUSION: The presence of silent cerebral infarcts on MRI is an independent predictor of the risk of symptomatic stroke over a 4-year follow- up in older individuals without a clinical history of stroke.

}, keywords = {Aged, Cerebral Infarction, Cohort Studies, Female, Follow-Up Studies, Humans, Incidence, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Risk Factors, Stroke}, issn = {0028-3878}, doi = {10.1212/wnl.57.7.1222}, author = {Bernick, C and Kuller, L and Dulberg, C and Longstreth, W T and Manolio, T and Beauchamp, N and Price, T} } @article {869, title = {Statins and cognitive function in the elderly: the Cardiovascular Health Study.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1388-94}, abstract = {

OBJECTIVE: To examine the association of statin drug use on cognitive and MRI change in older adults.

METHODS: Participants in the Cardiovascular Health Study, a longitudinal study of people age 65 or older, were classified into three groups determined by whether they were taking statin drugs on a continuous basis, intermittently, or not at all. The untreated group was further divided into categories based on National Cholesterol Education Program recommendations for lipid-lowering treatment. Participants with prevalent or incident clinical TIA or stroke or with baseline Modified Mini-Mental State Examination (3MS) scores at or below 80 were excluded. Outcomes examined included rate of change on the 3MS over an average observational period of 7 years, along with changes in MRI white matter grade and measures of atrophy.

RESULTS: Three thousand three hundred thirty-four participants had adequate data for analysis. At baseline, the untreated group in which lipid-lowering drug treatment was recommended were slightly older, less likely to be on estrogen replacement, and had higher serum cholesterol and lower 3MS scores than the statin-treated group. The rate of decline on the 3MS was 0.48 point/year less in those taking statins compared with the untreated group for which treatment was recommended (p = 0.069) and 0.49 point/year less in statin users compared with the group in which lipid-lowering treatment was not recommended (p = 0.009). This effect remained after controlling for serum cholesterol levels. One thousand seven hundred thirty participants with baseline 3MS scores of > 80 underwent cranial MRI scans on two occasions separated by 5 years. There was no significant difference in white matter grade change or atrophy measures between groups.

CONCLUSION: Statin drug use was associated with a slight reduction in cognitive decline in an elderly population. This relationship could not be completely explained by the effect of statins on lowering of serum cholesterol.

}, keywords = {Aged, Aged, 80 and over, Aging, Anticholesteremic Agents, Atrophy, Brain, Cholesterol, Cognition Disorders, Cohort Studies, Dementia, Female, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Longitudinal Studies, Male, Memory Disorders, Nootropic Agents, Treatment Outcome}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000182897.18229.ec}, author = {Bernick, C and Katz, R and Smith, N L and Rapp, S and Bhadelia, R and Carlson, M and Kuller, L} }