Biomedical subjects

Alexa Beiser

Publications and source records attributed to Alexa Beiser.

At least 19 recordsLinked to original sources

PubMed2006

Trends in incidence, lifetime risk, severity, and 30-day mortality of stroke over the past 50 years.

CONTEXT: Prior estimates of long-term trends in the incidence and severity of stroke have varied; trends in lifetime risk have not been reported. OBJECTIVE: To determine long-term trends in the incidence, lifetime risk, severity, and 30-day mortality of clinical stroke. DESIGN, SETTING, AND PARTICIPANTS: Prospective evaluation of the community-based Framingham Study original and offspring cohorts. Participants were 9152 men and women free of prevalent stroke and undergoing follow-up for up to 50 years over 3 consecutive periods (1950-1977, 1978-1989, and 1990-2004), with biennial ascertainment of stroke risk factor data and active surveillance for incident clinical stroke and cause-specific mortality. MAIN OUTCOME MEASURES: Incidence (age-adjusted, sex-specific), severity, 30-day mortality, and mortality-adjusted 10-year and lifetime risk of stroke in each of the specified periods. RESULTS: There were 1030 incident clinical strokes (450 [44%] in men, 629 atherothrombotic brain infarctions [61%]) in 9152 persons 55 years or older over 174,917 person-years of follow-up. The age-adjusted incidence of first stroke per 1000 person-years in each of the 3 periods was 7.6, 6.2, and 5.3, respectively, in men (P = .02 for trend) and 6.2, 5.8, and 5.1 in women (P = .01 for trend). The lifetime risk at age 65 years decreased from 19.5% to 14.5% in men (P = .11) and from 18.0% to 16.1% in women (P = .61). Age-adjusted stroke severity did not vary across periods; however, 30-day mortality decreased significantly in men (from 23% to 14%; P = .01) but not significantly in women (from 21% to 20%; P = .32). CONCLUSIONS: In this cohort of men and women free of prevalent clinical stroke at initial examination, incidence of stroke has decreased over the past 50 years but the lifetime risk has not declined to the same degree, perhaps due to improved life expectancy. The results of this study suggest that improved control of risk factors has lowered stroke incidence but emphasize the need for continued primary prevention efforts.

Adult↗

PubMed2006

Depressive symptoms and risk of stroke: the Framingham Study.

BACKGROUND AND PURPOSE: Emerging evidence raises the possibility of an association between depression and stroke risk. This study sought to examine whether depressive symptoms are associated with an increased risk of cerebrovascular events in a community-based sample. METHODS: A prospective study was conducted on 4120 Framingham Heart Study participants aged 29 to 100 years with up to 8 years of follow-up. The Center for Epidemiologic Studies Depression Scale was used to measure depressive symptoms. Incident stroke and transient ischemic attack (TIA) events were assessed by uniform diagnostic criteria. The association between depressive symptoms and risk of stroke/TIA was analyzed with Cox proportional-hazards models, after adjusting for traditional stroke risk factors. RESULTS: In participants <65 years, the risk of developing stroke/TIA was 4.21 times greater (P= <0.001) in those with symptoms of depression. After adjusting for components of the Framingham Stroke Risk Profile (hazard ratio=3.43, 95% CI=1.60 to 7.36, P=0.002) and education (hazard ratio=4.89, 95% CI=2.19 to 10.95), similar results were obtained. In subjects aged 65 and older, depressive symptoms were not associated with an increased risk of stroke/TIA. Taking antidepressant medications did not alter the risk associated with depressive symptoms. CONCLUSIONS: In this community-based study, depressive symptoms were an independent risk factor for incident stroke/TIA in individuals <65 years. These data suggest that identification of depressive symptoms at younger ages may have an impact on the primary prevention of stroke.

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PubMed2006

Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age.

BACKGROUND: Lifetime risk for atherosclerotic cardiovascular disease (CVD) has not previously been estimated, and the effect of risk factor burden on lifetime risk is unknown. METHODS AND RESULTS: We included all Framingham Heart Study participants who were free of CVD (myocardial infarction, coronary insufficiency, angina, stroke, claudication) at 50 years of age. Lifetime risks to 95 years of age were estimated for men and women, with death free of CVD as a competing event. We followed up 3564 men and 4362 women for 111,777 person-years; 1757 had CVD events and 1641 died free of CVD. At 50 years of age, lifetime risks were 51.7% (95% CI, 49.3 to 54.2) for men and 39.2% (95% CI, 37.0 to 41.4) for women, with median survivals of 30 and 36 years, respectively. With more adverse levels of single risk factors, lifetime risks increased and median survivals decreased. Compared with participants with > or =2 major risk factors, those with optimal levels had substantially lower lifetime risks (5.2% versus 68.9% in men, 8.2% versus 50.2% in women) and markedly longer median survivals (>39 versus 28 years in men, >39 versus 31 years in women). CONCLUSIONS: The absence of established risk factors at 50 years of age is associated with very low lifetime risk for CVD and markedly longer survival. These results should promote efforts aimed at preventing development of risk factors in young individuals. Given the high lifetime risks and lower survival in those with intermediate or high risk factor burden at 50 years of age, these data may be useful in communicating risks and supporting intensive preventive therapy.

Age Factors↗

PubMed2006

The lifetime risk of stroke: estimates from the Framingham Study.

BACKGROUND AND PURPOSE: The lifetime risk (LTR) of stroke has not been reported for the United States population; such data would assist public education and health planning. METHODS: Framingham Original cohort participants (n=4897) who were stroke- and dementia-free at 55 years of age were followed biennially for up to 51 years (115 146 person years). We estimated the sex-specific 10-, 20-, and 30-year risks and LTR of developing a stroke by baseline age and blood pressure (BP) and compared it with the risk of developing Alzheimer disease (AD). RESULTS: A total of 875 participants (522 women) developed a first-ever stroke; 749 (448 women) had an ischemic stroke. LTR of stroke was high and remained similar at ages 55, 65, and 75 years, approximating 1 in 5 for women and 1 in 6 for men. Participants with a normal BP (<120/80 mm Hg) had approximately half the LTR of stroke compared with those with high BP (> or =140/90 mm Hg). The LTR of AD at age 65 (292 participants; 211 women) approximated 1 in 5 for women and 1 in 10 for men. The LTR of developing either stroke or dementia approximated 1 in 3 in both sexes. CONCLUSIONS: The LTR of stroke in middle-aged adults is 1 in 6 or more, which is equal to or greater than the LTR of AD. Women had a higher risk because of longer life expectancy. BP is a significant determinant of the LTR of stroke, and promotion of normal BP levels in the community might be expected to substantially reduce this risk.

Age Factors↗

PubMed2006

Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study.

BACKGROUND: Diabetes mellitus (DM) could increase the risk of Alzheimer disease (AD) through several biologically plausible pathways, but the relationship between DM and the development of AD remains uncertain. OBJECTIVE: To compare the risk of developing AD in subjects with and without DM. DESIGN: Prospective community-based cohort study. PARTICIPANTS: Framingham Study Original cohort participants who were dementia free and attended the 16th biennial examination (n = 2210 persons, 1325 women; mean age, 70 years). MAIN OUTCOME MEASURES: Relative risk of incident AD (criteria from the National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) associated with baseline DM (casual plasma glucose >or=200 mg/dL [>or=11.1 mmol/L] or use of insulin or a hypoglycemic drug) in overall group and within subgroups defined by apolipoprotein E genotype and plasma homocysteine levels; models were adjusted for age, sex, and cardiovascular risk factors. RESULTS: At baseline, 202 participants (9.1%) had DM. During the follow-up period (mean, 12.7 years; range, 1-20 years), 17 of 202 persons with DM (8.4%) and 220 of 2008 persons without DM (11.0%) developed AD, yielding a relative risk of 1.15 (95% confidence interval, 0.65-2.05). Among subjects without an apolipoprotein E epsilon4 allele or elevated plasma homocysteine levels, 44 of 684 persons (6.4%) developed AD; relative risk for AD comparing diabetic patients with nondiabetic patients was 2.98 (95% confidence interval, 1.06-8.39; P = .03). The effect was strongest in persons aged 75 years or older with a relative risk of 4.77 (95% confidence interval, 1.28-17.72; P = .02). CONCLUSION: Diabetes mellitus did not increase the risk of incident AD in the Framingham cohort overall; however, DM may be a risk factor for AD in the absence of other known major AD risk factors.

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PubMed2006

Association of white matter hyperintensity volume with decreased cognitive functioning: the Framingham Heart Study.

OBJECTIVE: To examine the relationship between white matter hyperintensity (WMH) volume on magnetic resonance images and cognitive tests in a large, population-based sample. METHODS: Quantitative magnetic resonance imaging and neuropsychological evaluations were performed in 1820 dementia- and stroke-free participants from the Framingham Offspring Cohort. The WMH volume relative to total cranial volume was computed; WMH volumes more than 1 SD above the age-predicted mean were defined as large. Adjusting for age, sex, education, height, and Framingham Stroke Risk Profile, we examined the relationship between WMH and 3 cognitive factors derived from a neuropsychological test battery (verbal memory, visuospatial memory and organization, and visual scanning and motor speed) and 3 individual measures of new learning, abstract reasoning, and naming. RESULTS: Compared with those with no or little WMH volume, participants with large WMH volume performed worse on the cognitive factors of visuospatial memory and organization (P = .04) and visual scanning and motor speed (P = .01), as well as on new learning (P = .04), but not on verbal memory (P = .52). CONCLUSIONS: In this younger community-based population of nondemented individuals, those with large WMH volume, as compared with those with less or no WMH volumes, performed significantly worse in cognitive domains generally associated with frontal lobe systems and, to a lesser extent, the medial temporal area. Further study will clarify whether large WMH volume and associated cognitive impairment lead to future risk of stroke or dementia.

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PubMed2005

Genome-wide scan for white matter hyperintensity: the Framingham Heart Study.

BACKGROUND AND PURPOSE: White matter hyperintensity (WMH) volume is associated with aging and cerebrovascular disease and has been demonstrated to have a high heritability in the Framingham Heart Study as well as in other studies. We performed a genome-wide linkage analysis to identify chromosomal regions that may harbor genes influencing WMH in a family-based sample of the Framingham Heart Study. METHODS: Brain magnetic resonance scans were performed, and WMH and total cranial volume (TCV) were quantified as previously described on 2259 cohort and offspring participants. The outcome used for linkage analysis was an age specific (within 10-year age groups) z-score for the natural logarithm of the ratio of WMH to TCV. This z-score was based on 2230 individuals after excluding 26 participants with neurological conditions other than stroke and 3 individuals whose ages were out of range. Variance component linkage analysis included 747 individuals (mean age=62.16+/-12.43 years) with both magnetic resonance measure and genotype information in 237 families. Mean percent WMH to TCV was 0.098+/-0.175 with a range of 0.00025% to 1.37% in the linkage analysis subjects. RESULTS: A maximum multipoint logarithm of the odds (LOD) score=3.69, which indicates significant evidence of linkage, was observed at 4 cM on chromosome 4. A suggestive peak with LOD=1.78 was observed at 95 cM on chromosome 17. CONCLUSIONS: We have significant evidence that a gene influencing WMH volume is located on chromosome 4 of the human genome.

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PubMed2005

Homocysteine and cognitive performance in the Framingham offspring study: age is important.

Plasma total homocysteine (tHcy) concentrations are associated with deficits in cognitive performance in persons free from dementia. The extent to which age modifies these associations is in need of further investigation in large, community-based, prospective studies combining the following elements: 1) multiple cognitive tests; 2) statistical adjustment for the role of the vitamin cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence of risk factors for cardiovascular disease and stroke. Using data collected between 1991 and 2002, the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study, who were stratified into three age groups (40-49 years, 50-59 years, 60-82 years), after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures. Regardless of statistical adjustment for age, sex, gender, the vitamin cofactors, and cardiovascular risk factors, statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years; no such associations were observed for participants aged less than 60 years. Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age.

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PubMed2005

Bone mineral density and the risk of Alzheimer disease.

BACKGROUND: Some, but not all, studies have suggested that estrogen replacement therapy has a beneficial effect on cognition in postmenopausal women. Bone mineral density (BMD) is a potential surrogate marker for cumulative estrogen exposure and has been associated with cognitive performance and risk of cognitive deterioration. OBJECTIVE: To examine whether low BMD in elderly individuals is associated with an increased risk of developing Alzheimer disease (AD). DESIGN, SETTING, AND PARTICIPANTS: Community-based prospective cohort study of 987 subjects (610 women) who were cognitively intact and had baseline BMD measured at the femoral neck, the trochanter, and the radial shaft between 1988 and 1989. MAIN OUTCOME MEASURES: Incidence of AD and all-cause dementia during an 8-year follow-up period. RESULTS: Women in the lowest quartile of femoral neck BMD had more than twice the incidence of AD (hazard ratio, 2.04; 95% confidence interval, 1.11-3.75) and all-cause dementia (hazard ratio, 2.01; 95% confidence interval, 1.16-3.49) compared with those in higher quartiles after adjusting for age, sex, apolipoprotein E epsilon4, baseline homocysteine level, education, estrogen use, smoking, and stroke. A similar but statistically nonsignificant relationship was observed between BMD of the femoral trochanter and AD, while no such relationship was seen between radial BMD and AD or all-cause dementia. In men, there was a trend toward an inverse relationship between BMD and the risk of AD, but the relationship was not statistically significant at any of the 3 sites. CONCLUSIONS: Low femoral neck BMD was associated with approximately 2 times the risk of AD and all-cause dementia in women but not men, suggesting the possibility that cumulative estrogen exposure may influence the risk of developing AD. Additional studies are needed to confirm this correlation.

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PubMed2005

Measures of brain morphology and infarction in the framingham heart study: establishing what is normal.

Numerous anatomical and brain imaging studies find substantial differences in brain structure between men and women across the span of human aging. The ability to extend the results of many of these studies to the general population is limited, however, due to the generally small sample size and restrictive health criteria of these studies. Moreover, little attention has been paid to the possible impact of brain infarction on age-related differences in regional brain volumes. Given the current lack of normative data on gender and aging related differences in regional brain morphology, particularly with regard to the impact of brain infarctions, we chose to quantify brain MRIs from more than 2200 male and female participants of the Framingham Heart Study who ranged in age from 34 to 97 years. We believe that MRI analysis of the Framingham Heart Study more closely represents the general population enabling more accurate estimates of regional brain changes that occur as the consequence of normal aging. As predicted, men had significantly larger brain volumes than women, but these differences were generally not significant after correcting for gender related differences in head size. Age explained approximately 50% of total cerebral brain volume differences, but age-related differences were generally small prior to age 50, declining substantially thereafter. Frontal lobe volumes showed the greatest decline with age (approximately 12%), whereas smaller differences were found for the temporal lobes (approximately 9%). Age-related differences in occipital and parietal lobe were modest. Age-related gender differences were generally small, except for the frontal lobe where men had significantly smaller lobar brain volumes throughout the age range studied. The prevalence of MRI infarction was common after age 50, increased linearly with age and was associated with significantly larger white matter hyperintensity (WMH) volumes beyond that associated with age-related differences in these measures. Amongst men, the presence of MRI infarction was associated with significant age-related reductions in total brain volume. Finally, statistically significant associations were found between the volume of MRI infarcts in cubic centimeters and all brain measures with the exception of parietal lobe volume for individuals where the volume of MRI infarctions was measured. These data serve to define age and gender differences in brain morphology for the Framingham Heart Study. To the degree participants of the Framingham Heart Study are representative the general population, these data can serve as norms for comparison with morphological brain changes associated with aging and disease. In this regard, these cross-sectional quantitative estimates suggest that age-related tissue loss differs quantitatively and qualitatively across brain regions with only minor differences between men and women. In addition, MRI evidence of cerebrovascular disease is common to the aging process and associated with smaller regional brain volumes for a given age, particularly for men. We believe quantitative MRI studies of the Framingham community enables exploration of numerous issues ranging from understanding normal neurobiology of brain aging to assessing the impact of various health factors, particularly those related to cerebrovascular disease, that appear important to maintaining brain health for the general population.

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PubMed2004

Lifetime risk for development of atrial fibrillation: the Framingham Heart Study.

BACKGROUND: Atrial fibrillation (AF) is the most common cardiac dysrhythmia and a source of considerable morbidity and mortality, but lifetime risk for AF has not been estimated. METHODS AND RESULTS: We included all participants in the Framingham Heart Study who were free of AF at index ages of 40 years and older. We estimated lifetime risks for AF (including atrial flutter) to age 95 years, with death free of AF as a competing event. We followed 3999 men and 4726 women from 1968 to 1999 (176 166 person-years); 936 participants had development of AF and 2621 died without prior AF. At age 40 years, lifetime risks for AF were 26.0% (95% CI, 24.0% to 27.0%) for men and 23.0% (21.0% to 24.0%) for women. Lifetime risks did not change substantially with increasing index age despite decreasing remaining years of life because AF incidence rose rapidly with advancing age. At age 80 years, lifetime risks for AF were 22.7% (20.1% to 24.1%) in men and 21.6% (19.3% to 22.7%) in women. In further analyses, counting only those who had development of AF without prior or concurrent congestive heart failure or myocardial infarction, lifetime risks for AF were approximately 16%. CONCLUSIONS: Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. Lifetime risks for AF are high (1 in 6), even in the absence of antecedent congestive heart failure or myocardial infarction. These substantial lifetime risks underscore the major public health burden posed by AF and the need for further investigation into predisposing conditions, preventive strategies, and more effective therapies.

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PubMed2004

Framingham risk score and prediction of lifetime risk for coronary heart disease.

We investigated whether the Framingham risk score, which was designed to estimate the 10-year risk of coronary heart disease (CHD), differentiates lifetime risk for CHD. All subjects in the Framingham Heart Study examined from 1971 to 1996 who were free of CHD were included. Subjects were stratified into age- and gender-specific tertiles of Framingham risk score, and lifetime risk for CHD was estimated. We followed 2,716 men and 3,500 women; 939 developed CHD and 1,363 died free of CHD. At age 40 years, in risk score tertiles 1, 2, and 3, respectively, the lifetime risks for CHD were 38.4%, 41.7%, and 50.7% for men and 12.2%, 25.4%, and 33.2% for women. At age 80 years, risks were 16.4%, 17.4%, and 38.8% for men and 12.8%, 22.4%, and 27.4% for women. The Framingham risk score stratified lifetime risk well for women at all ages. It performed less well in younger men but improved at older ages as remaining life expectancy approached 10 years. Lifetime risks contrasted sharply with shorter term risks: at age 40 years, the 10-year risks of CHD in tertiles 1, 2, and 3, respectively, were 0%, 2.2%, and 11.6% for men and 0%, 0.7%, and 2.3% for women. The Framingham 10-year CHD risk prediction model discriminated short-term risk well for men and women. However, it may not identify subjects with low short-term but high lifetime risk for CHD, likely due to changes in risk factor status over time. Further work is needed to generate multivariate risk models that can reliably predict lifetime risk for CHD.

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PubMed2004

Stroke risk profile predicts white matter hyperintensity volume: the Framingham Study.

BACKGROUND AND PURPOSE: Previous studies of cardiovascular risk factors and white matter hyperintensity (WMH) on brain MRI have been limited by the failure to exclude symptomatic cerebrovascular disease and dementia or by the use of semiquantitative rather than quantitative methods to measure WMH volume (WMHV). We examined the relationship between Framingham Stroke Risk Profile (FSRP) and WMHV measured quantitatively in a stroke and dementia-free subset of the Framingham Offspring Cohort. METHODS: Brain MRI was performed in 1814 members of the Framingham Offspring Cohort. Pixel-based quantitative measures of WMHV corrected for head size were obtained using a semiautomated algorithm. WMHV was not normally distributed and therefore was log-transformed (LWMHV). The FSRP and its component risk factors measured a mean of 7.5 years before MRI were related to both continuous measures of LWMHV and to the presence of large volumes of LWMHV (LWMHV-large). All analyses were adjusted for age and sex. RESULTS: FSRP was strongly associated with LWMHV and LWMHV-large. Age, smoking, history of cardiovascular disease, hypertension, and left ventricular hypertrophy by electrocardiogram were all significantly related to LWMHV or LWMHV-large. CONCLUSIONS: FSRP and several cardiovascular risk factors were related to both WMHV measured continuously and to a categorical designation of large volumes of WMH. These findings provide strong evidence of a vascular basis for WMH.

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PubMed2004

Cerebral microbleeds: prevalence and associations with cardiovascular risk factors in the Framingham Study.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are areas of low signal intensity on gradient echo T2*-weighted magnetic resonance imaging (T2*MRI) corresponding to hemosiderin deposits in the perivascular space. Microangiopathy from atherosclerosis or amyloid angiopathy might lead to the formation of these lesions; therefore, there may be associations between CMBs and cardiovascular risk factors, APOE allele status, and brain morphology. We examined these relationships in the Framingham Study (FHS). METHODS: In 472 subjects from the FHS Offspring and Cohort, we related CMB status to age, sex, systolic blood pressure, total cholesterol and high-density lipoprotein cholesterol (HDL-C) levels, smoking, diabetes, total hemispheric brain volume, white matter hyperintensity volume (WMHV), and APOE allele status. RESULTS: Overall prevalence of CMBs was 4.7%, but CMBs were more prevalent with advanced age and male sex. Blood pressure, brain volume, and WMHV were related to CMBs in crude analysis but not after adjustment for age and sex. There were no significant relationships demonstrated between CMBs and APOE allele status, cholesterol, smoking, or diabetes. CONCLUSIONS: There is a low prevalence of CMBs in the community and a strong relationship with increasing age and male sex. We found no independent relationships with cardiovascular risk factors, APOE status, brain volumes, or WMH.

Age Factors↗

PubMed2004

Genetic variation in white matter hyperintensity volume in the Framingham Study.

BACKGROUND AND PURPOSE: In a previous study of normal elderly male twins, the heritability of quantitative white matter hyperintensity (WMH) volume has been estimated to be high (0.73). We investigated heritability of WMH in a family-based sample of the Framingham Heart Study for sex differences and the impact of age. METHODS: Brain magnetic resonance scans were performed on 2012 individuals in the cohort and offspring of the Framingham study. This report was limited to 1330 stroke-free and dementia-free members (mean age 61.0 years) of the Framingham offspring. Individuals with a history of multiple sclerosis, stroke, dementia, or other neurological condition including traumatic brain injury were excluded from this analysis. WMH volume and total cranial volume (TCV) were quantified using a previously published algorithm. Because of extreme skewing, measures of WMH were log-transformed before analysis. Variance components methods were used to estimate heritability of WMH after adjusting for sex, age, age2, and TCV. RESULTS: In the full dataset, WMH heritability was 0.55 (P<0.0001). Heritability among women was 0.78 (P<0.0001) whereas heritability among men was 0.52 (P<0.0003). Heritability varied as average age increased, with a peak of 0.68 (P<0.0001) in individuals aged 55 or older. CONCLUSIONS: Using a family-based study design comprising generally healthy individuals, this study found high heritability of WMH overall and similar heritability for both men and women. In addition, the heritability of WMH remained high among individuals in whom the prevalence of cerebrovascular brain injury was generally low, suggesting that WMH is also likely to be an excellent genetic marker of brain aging.

Adult↗

PubMed2004

Dementia after stroke: the Framingham Study.

BACKGROUND AND PURPOSE: Identification of risk factors for dementia after stroke is best performed in comparison with stroke-free controls, because older subjects at high risk for stroke also have a substantial risk of dementia in the absence of stroke. Previous case-control studies were hospital-based. We used a nested case-control design to prospectively evaluate these risk factors in the community-based Framingham Study cohort. METHODS: We compared 212 subjects who were free of dementia in January 1982 and sustained a first stroke after this date, with 1060 age- and sex-matched, stroke- and dementia-free controls. We calculated 10-year risks of dementia (by Diagnostic and Statistical Manual of Mental Disorders, Volume IV criteria) developing in cases and controls and also estimated the hazard ratios within subgroups defined by exposure to various demographic factors (age, gender, education), stroke-related features (right or left hemisphere, stroke type, second stroke), stroke risk factors (hypertension, diabetes, atrial fibrillation, smoking) and apolipoprotein E genotype. RESULTS: Dementia developed in 19.3% of cases and 11.0% of controls. Baseline stroke doubled the risk of dementia (hazard ratio [HR]: 2.0; 95% confidence interval [CI]: 1.5 to 3.1) and adjustment for age, sex, education, and exposure to individual stroke risk factors did not diminish the risk (HR: 2.4; 95% CI: 1.6 to 3.7). The HR was higher in younger subjects (age younger than 80 years [HR: 2.6; 95% CI: 1.5 to 4.5]), apolipoprotein E 3/3 homozygotes (HR: 3.4; 95% CI: 2.0 to 5.8), and high school graduates (HR: 2.4; 95% CI: 1.5 to 3.9). CONCLUSIONS: Stroke increases a subject's risk of dementia as compared with age- and sex-matched controls. Primary and secondary prevention of stroke should significantly decrease the risk of all dementia.

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PubMed2004

Managing and analysing data from a large-scale study on Framingham Offspring relating brain structure to cognitive function.

At the Framingham Heart Study under separate research grant funding from the National Institute of Aging, NIH, we are gathering brain structure and cognitive information on the Framingham Offspring, creating one of the largest known data sets to assess changes in brain structure associated with normative ageing and cognitive decline. Subject recruitment, data collection, data management and statistical analysis require a collaborative integrated effort on the part of the Framingham project team. Here we describe this effort, as well as the various brain structure and cognitive function parameters we are now collecting. We are currently performing analyses of data collected through 2002, and we discuss the statistical issues arising relating brain structure parameters to cognitive function.

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PubMed2004

Framingham stroke risk profile and lowered cognitive performance.

BACKGROUND AND PURPOSE: The primary objective of this work was to describe the relationships between 10-year risk for stroke and multiple measures of cognitive performance for a large community-based sample of individuals who were free of clinical stroke and dementia at the time of risk assessment. METHODS: Participants were 1011 men and 1164 women from the Framingham Offspring Study. The Framingham Stroke Risk Profile was used to assess 10-year risk of stroke. Using a cross-sectional design, we assessed 10-year risk of stroke, the predictor variable, and cognitive performance, the outcome variable, at examination 7 of the Framingham Offspring Study. Multivariable linear regression models were used to relate 10-year risk of stroke to cognitive tests measuring multiple domains of cognitive functioning. RESULTS: With statistical adjustment for age, education, sex, and other correlates of both stroke and cognitive ability, an inverse association between increments in 10-year risk of stroke and cognitive performance level was observed for tests indexing visual-spatial memory, attention, organization, scanning, and abstract reasoning. CONCLUSIONS: In stroke- and dementia-free individuals, higher 10-year risk for stroke is associated with performance decrements in multiple cognitive domains.

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