@article {1449, title = {Methods of assessing prevalent cardiovascular disease in the Cardiovascular Health Study.}, journal = {Ann Epidemiol}, volume = {5}, year = {1995}, month = {1995 Jul}, pages = {270-7}, abstract = {

The objective of this article is to describe the methods of assessing cardiovascular conditions among older adults recruited to the Cardiovascular Health Study (CHS), a cohort study of risk factors for coronary disease and stroke. Medicare eligibility lists from four US communities were used to obtain a representative sample of 5201 community-dwelling elderly, who answered standardized questionnaires and underwent an extensive clinic examination at baseline. For each cardiovascular condition, self-reports were confirmed by components of the baseline examination or, if necessary, by a validation protocol that included either the review of medical records or surveys of treating physicians. Potential underreporting of a condition was detected either by the review of medical records at baseline for other self-reported conditions or, during prospective follow-up, by the investigation of potential incident events. For myocardial infarction, 75.5\% of the self-reports in men and 60.6\% in women were confirmed. Self-reported congestive heart failure was confirmed in 73.3\% of men and 76.6\% of women; stroke, in 59.6\% of men and 53.8\% of women; and transient ischemic attack, in 41.5\% of men and 37.0\% of women. Underreporting was also common. During prospective follow-up of an average of about 3 years per person, approximately 50\% of men and 38\% of women were hospitalized or investigated for at least one potential incident event; for each cardiovascular condition, about 1 to 4\% of those investigated during prospective follow-up were found to have had the cardiovascular condition prior to entry into the cohort.(ABSTRACT TRUNCATED AT 250 WORDS)

}, keywords = {Aged, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Electrocardiography, Epidemiologic Methods, False Negative Reactions, Female, Humans, Male, Population Surveillance, Prevalence, Prospective Studies, Reproducibility of Results, Risk Factors, Self Disclosure, United States}, issn = {1047-2797}, author = {Psaty, B M and Kuller, L H and Bild, D and Burke, G L and Kittner, S J and Mittelmark, M and Price, T R and Rautaharju, P M and Robbins, J} } @article {1415, title = {Subclinical disease as an independent risk factor for cardiovascular disease.}, journal = {Circulation}, volume = {92}, year = {1995}, month = {1995 Aug 15}, pages = {720-6}, abstract = {

BACKGROUND: The primary aim of the present study was to determine the relation between measures of subclinical cardiovascular disease and the incidence of clinical cardiovascular disease among 5201 adults 65 years of age or older who were participating in the Cardiovascular Health Study.

METHODS AND RESULTS: A new method of classifying subclinical disease at baseline examination in the Cardiovascular Health Study included measures of ankle-brachial blood pressure, carotid artery stenosis and wall thickness, ECG and echocardiographic abnormalities, and positive response to the Rose Angina and Claudication Questionnaire. Participants were followed for an average of 2.39 years (maximum, 3 years). For participants without evidence of clinical cardiovascular disease at baseline, the presence of subclinical disease compared with no subclinical disease was associated with a significant increased risk of incident total coronary heart disease including CHD deaths and nonfatal MI and angina pectoris for both men and women. For individuals with subclinical disease, the increased risk of total coronary heart disease was 2.0 for men and 2.5 for women, and the increased risk of total mortality was 2.9 for men and 1.7 for women. The increased risk changed little after adjustment for other risk factors, including lipoprotein levels, blood pressure, smoking, and diabetes.

CONCLUSIONS: The measurement of subclinical disease provides an approach for identifying high-risk older individuals who may be candidates for more active intervention to prevent clinical disease.

}, keywords = {Aged, Cardiovascular Diseases, Cohort Studies, Coronary Disease, Female, Humans, Incidence, Longitudinal Studies, Male, Myocardial Infarction, Odds Ratio, Reference Values, Risk Factors}, issn = {0009-7322}, author = {Kuller, L H and Shemanski, L and Psaty, B M and Borhani, N O and Gardin, J and Haan, M N and O{\textquoteright}Leary, D H and Savage, P J and Tell, G S and Tracy, R} } @article {1464, title = {Correlates of thrombin markers in an elderly cohort free of clinical cardiovascular disease.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {16}, year = {1996}, month = {1996 Sep}, pages = {1163-9}, abstract = {

Studies suggest that thrombosis is important in the progression of atherosclerotic lesions. The biochemical markers prothrombin fragment 1-2 and fibrinopeptide A reflect in vivo thrombin generation and activity, respectively. As such, they are markers that might be associated with cardiovascular risk. From the Cardiovascular Health Study, a cohort study of 5201 persons over 65 years of age, 399 persons free of clinical cardiovascular disease (CVD) at the baseline examination were selected for study of specialized markers of hemostasis. We report the cross-sectional relationships of the thrombin markers to CVD risk factors and measures of subclinical CVD. The range of fragment 1-2 2 was 0.12 to 0.85 nmol/L. The range of fibrinopeptide A was 0.9 to 44.1 micrograms/L. High levels of fragment 1-2 and fibrinopeptide A were associated with age, with levels higher in women than men. Fragment 1-2 was associated with smoking; high levels of triglyceride, creatinine, and C-reactive protein; and low levels of glucose. Fibrinopeptide A was associated with high C-reactive protein and apolipoprotein(a) and lower ankle-brachial index. There were no significant associations of the thrombin markers with race, fibrinogen, alcohol consumption, diabetes, or most measures of subclinical CVD. Study findings support a hypothesis that there are physiological interrelationships between cardiac risk factors, hemostasis, inflammation, and progression of atherosclerosis.

}, keywords = {Aged, Biomarkers, Cardiovascular Diseases, Cohort Studies, Female, Hemostasis, Humans, Male, Risk Factors, Thrombin}, issn = {1079-5642}, author = {Cushman, M and Psaty, B M and Macy, E and Bovill, E G and Cornell, E S and Kuller, L H and Tracy, R P} } @article {1459, title = {Risk factors for abdominal aortic aneurysms in older adults enrolled in The Cardiovascular Health Study.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {16}, year = {1996}, month = {1996 Aug}, pages = {963-70}, abstract = {

B-mode ultrasound examinations of the abdominal aorta were performed from 1990 to 1992 to evaluate the prevalence of abdominal aortic aneurysm (AAA) in a subgroup of the Pittsburgh cohort (656 participants, aged 65 to 90 years) of the Cardiovascular Health Study (CHS). In this pilot study, we evaluated various definitions of aneurysm and the reproducibility of the measurements. In year 5 (1992 to 1993) of the CHS, the entire cohort (4741 participants) was examined. AAA was defined as an infrarenal aortic diameter of > or= 3.0 cm, or a ratio of infrarenal to suprarenal diameter of > or= 1.2, or a history of AAA repair. For the entire CHS cohort, prevalence of aneurysms was 9.5\% (451/4741) overall, with a prevalence among men of 14.2\% (278/1956) and prevalence among women of 6.2\% (173/2785). Variables significantly related to AAA were older age; male sex; history of angina, coronary heart disease, and myocardial infarction; lower ankle-arm blood pressure ratio; higher maximum carotid stenosis; greater intima-media thickness of the internal carotid artery; higher creatinine; lower HDL levels and higher LDL levels; and cigarette smoking. The study has documented the strong association of cardiovascular risk factors and measures of clinical and subclinical atherosclerosis and cardiovascular disease and prevalence of aneurysms. We used a definition that is more sensitive than previously reported (diameter or ratio), which allowed the detection of smaller aneurysms and possibly those at an earlier stage of development. Follow-up of this cohort may lead to new criteria for determining the risk factors for progression of aneurysms.

}, keywords = {Aged, Anthropometry, Aortic Aneurysm, Abdominal, Blood Pressure, Cardiovascular Diseases, Cohort Studies, Comorbidity, Female, Humans, Male, Middle Aged, Pilot Projects, Prevalence, Reproducibility of Results, Risk Factors, Smoking, Ultrasonography, United States}, issn = {1079-5642}, author = {Alcorn, H G and Wolfson, S K and Sutton-Tyrrell, K and Kuller, L H and O{\textquoteright}Leary, D} } @article {1488, title = {Incidence of and risk factors for atrial fibrillation in older adults.}, journal = {Circulation}, volume = {96}, year = {1997}, month = {1997 Oct 07}, pages = {2455-61}, abstract = {

BACKGROUND: This study aimed to describe the incidence of atrial fibrillation (AF) among older adults during 3 years of follow-up.

METHODS AND RESULTS: In this cohort study, 5201 adults > or = 65 years old were examined annually on four occasions between June 1989 and May 1993. At baseline, participants answered questionnaires and underwent a detailed examination that included carotid ultrasound, pulmonary function tests, ECG, and echocardiography. Subjects with a pacemaker or AF at baseline (n=357) were excluded. New cases of AF were identified from three sources: (1) annual self-reports, (2) annual ECGs, and (3) hospital discharge diagnoses. Cox proportional-hazards models were used to assess baseline risk factors as predictors of incident AF. Among 4844 participants, 304 developed a first episode of AF during an average follow-up of 3.28 years, for an incidence of 19.2 per 1000 person-years. The onset was strongly associated with age, male sex, and the presence of clinical cardiovascular disease. For men 65 to 74 and 75 to 84 years old, the incidences were 17.6 and 42.7, respectively, and for women, 10.1 and 21.6 events per 1000 person-years. In stepwise models, the use of diuretics, a history of valvular heart disease, coronary disease, advancing age, higher levels of systolic blood pressure, height, glucose, and left atrial size were all associated with an increased risk of AF. The use of beta-blockers and high levels of alcohol use, cholesterol, and forced expiratory volume in 1 second were associated with a reduced risk of AF.

CONCLUSIONS: The incidence of AF in older adults may be higher than estimated by previous population studies. Left atrial size appears to be an important risk factor, and the control of blood pressure and glucose may be important in preventing the development of AF.

}, keywords = {Adult, Aged, Atrial Fibrillation, Blood Glucose, Blood Pressure, Cerebrovascular Disorders, Cohort Studies, Coronary Disease, Electrocardiography, Female, Follow-Up Studies, Hospital Records, Humans, Incidence, Male, Prospective Studies, Risk Factors, United States}, issn = {0009-7322}, author = {Psaty, B M and Manolio, T A and Kuller, L H and Kronmal, R A and Cushman, M and Fried, L P and White, R and Furberg, C D and Rautaharju, P M} } @article {585, title = {Relationship of plasmin generation to cardiovascular disease risk factors in elderly men and women.}, journal = {Arterioscler Thromb Vasc Biol}, volume = {19}, year = {1999}, month = {1999 Mar}, pages = {499-504}, abstract = {

Plasmin-alpha2-antiplasmin complex (PAP) marks plasmin generation and fibrinolytic balance. We recently observed that elevated levels of PAP predict acute myocardial infarction in the elderly, yet little is known about the correlates of PAP. We measured PAP in 800 elderly subjects who were free of clinical cardiovascular disease in 2 cohort studies: the Cardiovascular Health Study and the Honolulu Heart Program. Median PAP levels did not differ between the Cardiovascular Health Study (6.05+/-1.46 nmol/L) and the Honolulu Heart Program (6.11+/-1.44 nmol/L), and correlates of PAP were similar in both cohorts. In CHS, PAP levels increased with age (r=0. 30), procoagulant factors (eg, factor VIIc, r=0.15), thrombin activity (prothrombin fragment F1+2, r=0.29), and inflammation-sensitive proteins (eg, fibrinogen, r=0.44; factor VIIIc, r=0.37). PAP was associated with increased atherosclerosis as measured by the ankle-arm index (AAI) (P for trend, }, keywords = {Aged, Aged, 80 and over, alpha-2-Antiplasmin, Antifibrinolytic Agents, Asian Continental Ancestry Group, Cohort Studies, Coronary Disease, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Fibrinolysin, Fibrinolysis, Humans, Insulin Resistance, Male, Multivariate Analysis, Myocardial Infarction, Plasminogen Activator Inhibitor 1, Risk Factors}, issn = {1079-5642}, doi = {10.1161/01.atv.19.3.499}, author = {Sakkinen, P A and Cushman, M and Psaty, B M and Rodriguez, B and Boineau, R and Kuller, L H and Tracy, R P} } @article {667, title = {Coronary artery calcification in older adults to age 99: prevalence and risk factors.}, journal = {Circulation}, volume = {104}, year = {2001}, month = {2001 Nov 27}, pages = {2679-84}, abstract = {

BACKGROUND: Coronary artery calcification has been proposed as a noninvasive method to assess cardiovascular disease (CVD) risk. However, the prevalence and risk factors for coronary artery calcification in populations >65 years have not been well studied.

METHODS AND RESULTS: Electron beam tomography was performed to assess coronary artery calcium (CAC) in 614 older adults aged, on average, 80 years (range, 67 to 99 years); 367 (60\%) were women, and 143 (23\%) were black. Calcium scores ranged from 0 to 5459. Median scores were 622 for men and 205 for women. Scores increased by age and were lower in blacks than in whites. Nine percent of subjects (n=57) had no CAC, and 31\% (n=190) had a score lower than 100. A history of CVD was associated with calcium score. Age, male sex, white race, CVD, triglyceride level, pack-years of smoking, and asthma, emphysema, or bronchitis (chronic obstructive pulmonary disease) were independently associated with CAC score in the fourth quartile.

CONCLUSIONS: A wide range of CAC scores was observed, suggesting adaptation with aging. CAC may have potential to predict CVD in older adults, but this remains to be determined.

}, keywords = {Age Distribution, Age Factors, Aged, Aged, 80 and over, Black People, Calcinosis, Calcium, Cohort Studies, Comorbidity, Coronary Angiography, Coronary Artery Disease, Coronary Vessels, Demography, Female, Humans, Logistic Models, Male, Predictive Value of Tests, Prevalence, Risk Factors, Sex Distribution, Sex Factors, Tomography, X-Ray Computed, White People}, issn = {1524-4539}, doi = {10.1161/hc4601.099464}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Feldman, A and Edmundowicz, D and Kuller, L H} } @article {652, title = {Prevalence of clinical and isolated subclinical cardiovascular disease in older adults with glucose disorders: the Cardiovascular Health Study.}, journal = {Diabetes Care}, volume = {24}, year = {2001}, month = {2001 Jul}, pages = {1233-9}, abstract = {

OBJECTIVE: Clinical cardiovascular disease (CVD) is highly prevalent among people with diabetes. However, there is little information regarding the prevalence of subclinical CVD and its relation to clinical CVD in diabetes and in the glucose disorders that precede diabetes.

RESEARCH DESIGN AND METHODS: Participants in the Cardiovascular Health Study, aged > or = 65 years (n = 5,888), underwent vascular and metabolic testing. Individuals with known disease in the coronary, cerebral, or peripheral circulations were considered to have clinical disease. Those without any clinical disease in whom CVD was detected by ultrasonography, electrocardiography, or ankle arm index in any of the three vascular beds were considered to have isolated subclinical disease.

RESULTS: Approximately 30\% of the cohort had clinical disease, and approximately 60\% of the remainder had isolated subclinical disease. In those with normal glucose status, isolated subclinical disease made up most of the total CVD. With increasing glucose severity, the proportion of total CVD that was clinical disease increased; 75\% of men and 66\% of women with normal fasting glucose status had either clinical or subclinical CVD. Among those with known diabetes, the prevalence was approximately 88\% (odds ratio [OR] 2.46 for men and 4.22 for women, P < 0.0001). There were intermediate prevalences and ORs for those with impaired fasting glucose status and newly diagnosed diabetes.

CONCLUSIONS: Isolated subclinical CVD is common among older adults. Glucose disorders are associated with an increased prevalence of total CVD and an increased proportion of clinical disease relative to subclinical disease.

}, keywords = {Aged, Angina Pectoris, Cardiovascular Diseases, Cerebrovascular Disorders, Cohort Studies, Diabetes Mellitus, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Electrocardiography, Female, Glucose Intolerance, Heart Diseases, Humans, Male, Peripheral Vascular Diseases, Prevalence, United States}, issn = {0149-5992}, doi = {10.2337/diacare.24.7.1233}, author = {Barzilay, J I and Spiekerman, C F and Kuller, L H and Burke, G L and Bittner, V and Gottdiener, J S and Brancati, F L and Orchard, T J and O{\textquoteright}Leary, D H and Savage, P J} } @article {661, title = {The relation of markers of inflammation to the development of glucose disorders in the elderly: the Cardiovascular Health Study.}, journal = {Diabetes}, volume = {50}, year = {2001}, month = {2001 Oct}, pages = {2384-9}, abstract = {

Several studies suggest that inflammation plays a role in the pathogenesis of some glucose disorders in adults. We tested this hypothesis in a longitudinal cohort study of older individuals who had normal fasting glucose (FG) values at baseline. We compared the baseline levels of six inflammatory markers in participants who had developed glucose disorders at follow-up with those of participants whose FG remained normal at follow-up. Participants were members of the Cardiovascular Health Study, a prospective study of risk factors for cardiovascular disease in adults > or =65 years. All 5,888 participants had baseline testing, including FG and markers of inflammation: white blood cell and platelet counts and albumin, fibrinogen, C-reactive protein (CRP), and factor VIIIc levels. At 3-4 years of follow-up, 4,481 (84.5\%) of those who were alive had FG levels retested. Participants who developed diabetes (n = 45) had higher median levels of CRP at baseline than those who remained normoglycemic. On multivariate analysis, those with elevated CRP levels (75th percentile [2.86 mg/l] vs. 25th percentile [0.82 mg/l]) were 2.03 times (95\% confidence intervals, 1.44-2.86) more likely to have diabetes on follow-up. Adjustment for confounders and other inflammatory markers did not appreciably change this finding. There was no relationship between the development of diabetes and other markers of inflammation. Inflammation, as measured by CRP levels, is associated with the development of diabetes in the elderly. Understanding the role of inflammation in the pathogenesis of glucose disorders in this age-group may lead to better classification and treatment of glucose disorders among them.

}, keywords = {Aged, Biomarkers, Blood Glucose, C-Reactive Protein, Cardiovascular Diseases, Cohort Studies, Diabetes Mellitus, Female, Humans, Hypoglycemia, Inflammation, Longitudinal Studies, Male, Reference Values, Risk Factors}, issn = {0012-1797}, doi = {10.2337/diabetes.50.10.2384}, author = {Barzilay, J I and Abraham, L and Heckbert, S R and Cushman, M and Kuller, L H and Resnick, H E and Tracy, R P} } @article {638, title = {The role of comorbidity in the assessment of intermittent claudication in older adults.}, journal = {J Clin Epidemiol}, volume = {54}, year = {2001}, month = {2001 Mar}, pages = {294-300}, abstract = {

The prevalence of intermittent claudication (IC) in older adults by questionnaire is less than 5\% while the prevalence of peripheral arterial disease (PAD) by non-invasive testing is 2-4-fold higher. Comorbid conditions may result in under-reporting intermittent claudication (IC) as assessed by the Rose Questionnaire. We examined characteristics of those who report leg pain in relationship to other comorbid conditions and disability in 5888 participants of the Cardiovascular Health Study (CHS). Older adults with exertional leg pain, not meeting criteria for IC, had a higher prevalence of PAD on non-invasive testing with the ankle-arm index than those without pain, as well as a higher prevalence of arthritis. The pattern of responses suggested that pain for both conditions was reported together. The Rose Questionnaire for IC is specific for PAD, but a negative questionnaire does not indicate a lack of symptoms, rather the presence of PAD along with other conditions that can cause pain.

}, keywords = {Aged, Angina Pectoris, Arterial Occlusive Diseases, Cerebrovascular Disorders, Cohort Studies, Comorbidity, Diabetes Mellitus, Female, Humans, Intermittent Claudication, Leg, Male, Prevalence, Sensitivity and Specificity, Surveys and Questionnaires}, issn = {0895-4356}, doi = {10.1016/s0895-4356(00)00308-5}, author = {Newman, A B and Naydeck, B L and Sutton-Tyrrell, K and Polak, J F and Kuller, L H} } @article {745, title = {Lack of association of the plasminogen activator inhibitor-1 4G/5G promoter polymorphism with cardiovascular disease in the elderly.}, journal = {J Thromb Haemost}, volume = {1}, year = {2003}, month = {2003 Aug}, pages = {1799-804}, abstract = {

Elevated circulating plasminogen activator inhibitor-1 (PAI-1) may increase risk of cardiovascular disease (CVD). The 4G allele of the 4G/5G PAI-1 promoter polymorphism is associated with higher levels of PAI-1. We examined the association of PAI-1 4G/5G genotype and CVD events in the elderly participants of the Cardiovascular Health Study (CHS). We measured 4G/5G genotype in a nested case-control study within the CHS. Cases included incident angina, myocardial infarction (MI), and stroke. 4G/5G genotype was not found to be associated with markers of fibrinolysis or CVD risk in the selected elderly cohort. There were no differences in genotype frequencies by case-control status (5G/5G frequency 16-22\%; chi2P= 0.07). The 5G allele was not associated with incident CVD events when individuals with at least one 5G allele were compared to 4G/4G homozygotes. The presence of at least one 4G allele was likewise not associated with incident CVD when those with 4G/4G and 4G/5G genotypes were compared to 5G/5G homozygotes. Our results suggest that the PAI-1 4G/5G promoter polymorphism is not associated CVD risk factors or incident CVD events in the elderly.

}, keywords = {African Continental Ancestry Group, Aged, Alleles, Cardiovascular Diseases, Case-Control Studies, Cohort Studies, European Continental Ancestry Group, Female, Genotype, Homozygote, Humans, Male, Myocardial Infarction, Plasminogen Activator Inhibitor 1, Polymorphism, Genetic, Promoter Regions, Genetic, Risk}, issn = {1538-7933}, doi = {10.1046/j.1538-7836.2003.00255.x}, author = {Crainich, P and Jenny, N S and Tang, Z and Arnold, A M and Kuller, L H and Manolio, T and Sharrett, A R and Tracy, R P} } @article {870, title = {Benefits of fatty fish on dementia risk are stronger for those without APOE epsilon4.}, journal = {Neurology}, volume = {65}, year = {2005}, month = {2005 Nov 08}, pages = {1409-14}, abstract = {

OBJECTIVE: To compare associations of lean fish vs fatty fish (tuna or other fish) intake with dementia, Alzheimer disease (AD), and vascular dementia (VaD) and in relation to APOE epsilon4 status in the Cardiovascular Health Cognition Study (CHCS).

METHODS: Fish intake was assessed by food frequency questionnaires. Incident dementia, AD, and VaD were determined through a series of cognitive tests, physician{\textquoteright}s assessment, and committee consensus. We used Cox proportional hazards regression to calculate hazard ratios of dementia, AD, and VaD with lean fried fish, fatty fish, or total fish intake, which were then stratified by the presence of APOE epsilon4.

RESULTS: Although consumption of lean fried fish had no protective effect, consumption of fatty fish more than twice per week was associated with a reduction in risk of dementia by 28\% (95\% CI: 0.51 to 1.02), and AD by 41\% (95\% CI: 0.36 to 0.95) in comparison to those who ate fish less than once per month. Stratification by APOE epsilon4 showed this effect to be selective to those without the epsilon4 allele. Adjustment by education and income attenuated the effect.

CONCLUSION: In the Cardiovascular Health Cognition Study, consumption of fatty fish was associated with a reduced risk of dementia and Alzheimer disease for those without the APOE epsilon4 allele.

}, keywords = {Aged, Alzheimer Disease, Apolipoprotein E4, Apolipoproteins E, Cohort Studies, Dementia, Dietary Fats, Unsaturated, Fatty Acids, Omega-3, Feeding Behavior, Female, Fish Oils, Fish Products, Food, Formulated, Genetic Predisposition to Disease, Humans, Incidence, Male, Risk Factors, Socioeconomic Factors, Surveys and Questionnaires}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000183148.34197.2e}, author = {Huang, T L and Zandi, P P and Tucker, K L and Fitzpatrick, A L and Kuller, L H and Fried, L P and Burke, G L and Carlson, M C} } @article {837, title = {Classification of vascular dementia in the Cardiovascular Health Study Cognition Study.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {2005 May 10}, pages = {1539-47}, abstract = {

OBJECTIVE: To describe the diagnostic classification of subjects with incident vascular dementia (VaD) participating in the Cardiovascular Health Study (CHS) Cognition Study.

METHODS: The CHS classified 480 incident cases between 1994 and 1999 among 3,608 CHS participants who had brain MRI in 1992 through 1994 and in 1997 through 1998. The patients were diagnosed before and after reviewing the brain MRI.

RESULTS: The pre-MRI classification showed that 52 participants had VaD and 76 had both Alzheimer disease (AD) and VaD. The post-MRI classification showed that the Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) criteria classified 61 subjects as having VaD, the National Institute of Neurological Disorders and Stroke-Association Internationale pour la Recherche et l{\textquoteright}Enseignement en Neurosciences (NINDS-AIREN) criteria classified 43 subjects as having probable VaD and 10 as possible VaD, and the State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Center (ADDTC) criteria classified 117 as having probable VaD and 96 as possible. The combination of the ADDTC and National Institute of Neurological and Communication Disorders and Stroke-Alzheimer{\textquoteright}s Disease and Related Disorders Association criteria was used to examine the spectrum of vascular disease in dementia. The dementia was attributable to only vascular factors in 56 cases (probable VaD); VaD coexisted with AD in 61 cases, although the VaD component was the leading cause of dementia (probable VaD with AD); AD was the leading cause of dementia in 61 cases (possible VaD and probable AD); and in 29 cases, it was not clear that either AD or VaD was the primary diagnosis (possible AD and possible VaD).

CONCLUSIONS: None of the clinical criteria for VaD identified the same group of subjects. The diagnosis of vascular dementia is difficult in epidemiologic studies because poststroke dementia can be due to Alzheimer disease (AD) and evidence of vascular disease can be found in the MRI of dementia cases without clinical strokes. Whether the clinical progression is related to AD pathology or vascular disease is difficult to establish.

}, keywords = {Aged, Aged, 80 and over, Alzheimer Disease, Brain, Cerebral Arteries, Cohort Studies, Dementia, Vascular, Diagnosis, Differential, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Predictive Value of Tests, Stroke, United States}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000159860.19413.C4}, author = {Lopez, O L and Kuller, L H and Becker, J T and Jagust, W J and DeKosky, S T and Fitzpatrick, A and Breitner, J and Lyketsos, C and Kawas, C and Carlson, M} } @article {838, title = {Determinants of vascular dementia in the Cardiovascular Health Cognition Study.}, journal = {Neurology}, volume = {64}, year = {2005}, month = {2005 May 10}, pages = {1548-52}, abstract = {

OBJECTIVE: The authors evaluated 3,375 participants without dementia at the time of MRI in 1991 to 1994 over 5.7 years for incident dementia and type of dementia.

METHODS: Incidence of and risk factors for vascular dementia (VaD) were measured using both pre-MRI and modified State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Centers (ADDTC) post-MRI review and further classified Alzheimer disease (AD) by the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer{\textquoteright}s Disease and Related Disorders Association (NINCDS-ADRDA) criteria.

RESULTS: Approximately 44\% (213) of 480 incident dementia cases were classified as possible or probable VaD by ADDTC. The incidence of VaD increased with age and was greater in blacks than whites. Risk factors for VaD included age, Modified Mini-Mental State Examination, high white matter grade, number of MRI infarcts, ventricular size, and history of stroke.

CONCLUSIONS: Vascular disease in the brain is prevalent among incident dementia cases. There is a substantial overlap between cases classified as Alzheimer disease by Neurological and Communicative Disorders and Stroke and the Alzheimer{\textquoteright}s Disease and Related Disorders Association and vascular dementia (VaD) by modified State of California Alzheimer{\textquoteright}s Disease Diagnostic and Treatment Centers criteria. The substantial contribution of vascular disease would be missed without inclusion of MRI. Treatment of risk factors for VaD could have an important impact on incidence of dementia.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Atrophy, Brain, Cardiovascular Diseases, Cerebral Arteries, Cerebral Infarction, Cohort Studies, Comorbidity, Continental Population Groups, Dementia, Vascular, Female, Humans, Lateral Ventricles, Magnetic Resonance Imaging, Male, Nerve Fibers, Myelinated, Neuropsychological Tests, Risk Factors, Sex Factors}, issn = {1526-632X}, doi = {10.1212/01.WNL.0000160115.55756.DE}, author = {Kuller, L H and Lopez, O L and Jagust, W J and Becker, J T and DeKosky, S T and Lyketsos, C and Kawas, C and Breitner, J C S and Fitzpatrick, A and Dulberg, C} } @article {954, title = {Physical activity and white matter lesion progression: assessment using MRI.}, journal = {Neurology}, volume = {68}, year = {2007}, month = {2007 Apr 10}, pages = {1223-6}, abstract = {

We evaluated the association between physical activity and changes in white matter lesions (WMLs) on MRI in a sample of 179 older adults comprising 59 incident cases of Alzheimer disease, 60 persons with mild cognitive impairment, and 60 persons who remained cognitively stable over a median 5-year follow-up. Physical activity was not significantly associated with a decreased rate of periventricular or deep WML progression.

}, keywords = {Activities of Daily Living, Aged, Alzheimer Disease, Cognition Disorders, Cohort Studies, Demyelinating Diseases, Disease Progression, Female, Humans, Magnetic Resonance Imaging, Male, Motor Activity, United States}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000259063.50219.3e}, author = {Podewils, L J and Guallar, E and Beauchamp, N and Lyketsos, C G and Kuller, L H and Scheltens, P} } @article {1034, title = {No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.}, journal = {Neurology}, volume = {70}, year = {2008}, month = {2008 Jun 10}, pages = {2291-8}, abstract = {

INTRODUCTION: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk.

METHODS: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs.

RESULTS: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6\%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95\% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5\%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7\% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13).

CONCLUSIONS: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.

}, keywords = {Acetaminophen, Adolescent, Adult, Aged, Aged, 80 and over, Alzheimer Disease, Amyloid beta-Peptides, Analgesics, Non-Narcotic, Anti-Inflammatory Agents, Non-Steroidal, Aspirin, Cohort Studies, Female, Humans, Male, Middle Aged, Neuroprotective Agents, Peptide Fragments, Proportional Hazards Models, Prospective Studies, Risk Factors}, issn = {1526-632X}, doi = {10.1212/01.wnl.0000313933.17796.f6}, author = {Szekely, C A and Green, R C and Breitner, J C S and {\O}stbye, T and Beiser, A S and Corrada, M M and Dodge, H H and Ganguli, M and Kawas, C H and Kuller, L H and Psaty, B M and Resnick, S M and Wolf, P A and Zonderman, A B and Welsh-Bohmer, K A and Zandi, P P} } @article {1101, title = {Predicting risk of dementia in older adults: The late-life dementia risk index.}, journal = {Neurology}, volume = {73}, year = {2009}, month = {2009 Jul 21}, pages = {173-9}, abstract = {

OBJECTIVE: To develop a late-life dementia risk index that can accurately stratify older adults into those with a low, moderate, or high risk of developing dementia within 6 years.

METHODS: Subjects were 3,375 participants in the Cardiovascular Health Cognition Study without evidence of dementia at baseline. We used logistic regression to identify those factors most predictive of developing incident dementia within 6 years and developed a point system based on the logistic regression coefficients.

RESULTS: Subjects had a mean age of 76 years at baseline; 59\% were women and 15\% were African American. Fourteen percent (n = 480) developed dementia within 6 years. The final late-life dementia risk index included older age (1-2 points), poor cognitive test performance (2-4 points), body mass index <18.5 (2 points), > or =1 apolipoprotein E epsilon4 alleles (1 point), cerebral MRI findings of white matter disease (1 point) or ventricular enlargement (1 point), internal carotid artery thickening on ultrasound (1 point), history of bypass surgery (1 point), slow physical performance (1 point), and lack of alcohol consumption (1 point) (c statistic, 0.81; 95\% confidence interval, 0.79-0.83). Four percent of subjects with low scores developed dementia over 6 years compared with 23\% of subjects with moderate scores and 56\% of subjects with high scores.

CONCLUSIONS: The late-life dementia risk index accurately stratified older adults into those with low, moderate, and high risk of developing dementia. This tool could be used in clinical or research settings to target prevention and intervention strategies toward high-risk individuals.

}, keywords = {Age Factors, Aged, Aged, 80 and over, Alcohol Drinking, Apolipoprotein E4, Body Mass Index, Carotid Stenosis, Cerebrum, Cognition Disorders, Cohort Studies, Coronary Artery Bypass, Dementia, Female, Genetic Markers, Health Status Indicators, Humans, Logistic Models, Male, Predictive Value of Tests, Risk Assessment, Risk Factors, Risk Reduction Behavior}, issn = {1526-632X}, doi = {10.1212/WNL.0b013e3181a81636}, author = {Barnes, D E and Covinsky, K E and Whitmer, R A and Kuller, L H and Lopez, O L and Yaffe, K} }