Mark Espeland - Academia.edu (original) (raw)

Papers by Mark Espeland

Alzheimers & Dementia, Jul 1, 2014

Background: Spatial gradients in cortical thinning are a hallmark of dementias, and are shown to ... more Background: Spatial gradients in cortical thinning are a hallmark of dementias, and are shown to follow stereotypical patterns specific to each dementia. The signature of the disease is muchmore clearly visible in cortical thickness gradients taken between different brain regions, for example anterior-posterior gradients in AD as AD is known to affect the posterior cortices such as the medial temporal lobes, the precuneus etc. preferentially and early in the course of the disease. Keeping this idea of preferential gradient is mind, We reformulate our previously developed novel imaging cortical biomarker based on graph-theoretic analysis of inter-regional covariance of cortical thickness, called ThickNet features [1] to develop novel covariance features based on dissimilarity in thickness. These features capture the spatial thickness gradients within each subject. We call them Dissimilarity based Extraction of Covariance LInked NEtwork (DECLINE) features.We show that they outperform ThickNet features for the early detection of Alzheimer’s disease. DECLINE features are first of its kind and show promise in detecting the cognitive decline predictive of AD.Methods: Cortical thickness is extracted from the MRI scan using the method [2] for each patient and the features are registered to a common atlas surface to establish vertex-wise correspondence. Then the cortex of each patient is partitioned into large number (e.g. K1⁄4300 vertices per patch) of small areas by k-means clustering of vertices spatially on the atlas surface (Figure 1). A graph is then constructed by establishing a link between two such patches if dissimilarity (abs. difference inmean-thickness) in thickness is above a given threshold (e.g. 0.5mm). From this binary undirected graph, we compute several graph-theoretic properties called DECLINE features to represent each patient (See Figure 2), namely nodal degree, betweenness centrality and clustering coefficient. Using the same ADNI dataset on which we demonstrated the diagnostic utility of ThickNet features, we show that DECLINE features outperform ThickNet features, and show potential for the early detection of Alzheimer’s disease. Results: Using our Repeated Holdout, Stratified Training set (RHsT) cross-validation method proposed in [1] (See Figure 3), DECLINE features produced an area under ROC (AUC) of 0.93 in discriminating AD from healthy controls (CN), and an AUC of 0.87 in discriminating MCI converters (MCIc) from CN. The results presented in Figure 4 show DECLINE features significantly outperform ThickNet features in all the experiments. Conclusions: We present novel DECLINE measures based on inter-regional covariance of cortical thickness from structural MRI and demonstrate their performance on a benchmark ADNI dataset for early detection of Alzheimer’s disease.

Journal of the American Heart Association, Jan 2, 2017

Data are sparse regarding the value of physical activity (PA) surveillance among older adults-par... more Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). A...

Ageing Research Reviews, 2018

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying... more Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta

Stroke, 1999

Background and Purpose-It is generally assumed that risk factors affect extracranial carotid inti... more Background and Purpose-It is generally assumed that risk factors affect extracranial carotid intimal-medial thickness similarly among all arterial segments. This assumption underlies use of single segments or walls of segments as outcome variables for risk factor studies and clinical trials. However, if the impact of risk factors was unequal for various segments or circumferentially asymmetrical within segments, then inferences drawn from a single segment or wall might not be generalizable; furthermore, since individual segments and walls have unique histological characteristics and are differentially exposed to turbulent flow, risk factor relationships with a particular segment or wall may provide inferences regarding pathogenesis of atherosclerosis. Methods-We evaluated associations of risk factors with intimal-medial thickness at the near and far walls of the common carotid artery, bifurcation, and internal carotid artery in 280 individuals older than 45 years equally divided between coronary artery disease cases and controls and between men and women. Results-The patterns of differences in mean intimal-medial thickness among segments vary, depending on age, history of hypertension, body mass index in women, and coronary (case-control) status. The asymmetry of disease depended on blood glucose concentrations, prior history of diabetes, smoking, and coronary status. Sex, postmenopausal status, LDL cholesterol, systolic blood pressure, and history of myocardial infarction all had statistically significant relationships with intimal-medial thickness that were fairly homogeneous among arterial sites.

New England Journal of Medicine, 1997

Transvaginal ultrasonography is a noninvasive procedure that may be used to detect endometrial di... more Transvaginal ultrasonography is a noninvasive procedure that may be used to detect endometrial disease. However, its usefulness in screening for asymptomatic disease in postmenopausal women before or during treatment with estrogen or estrogen-progesterone replacement is not known. We compared the sensitivity and specificity of transvaginal ultrasonography and endometrial biopsy for the detection of endometrial disease in 448 postmenopausal women who received estrogen alone, cyclic or continuous estrogen-progesterone, or placebo for three years. Concurrent ultrasonographic and biopsy results were available for 577 examinations in the 448 women, 99 percent of whom were undergoing routine annual follow-up. Endometrial thickness was less than 5 mm in 45 percent of the examinations, 5 to 10 mm in 41 percent, more than 10 mm in 12 percent, and not measured in 2 percent, and it was higher in the women receiving estrogen alone than in the other groups. Biopsy detected 11 cases of serious disease: 1 case of adenocarcinoma, 2 cases of atypical simple hyperplasia, and 8 cases of complex hyperplasia. Biopsy also detected simple hyperplasia in 20 cases. At a threshold value of 5 mm for endometrial thickness, transvaginal ultrasonography had a positive predictive value of 9 percent for detecting any abnormality, with 90 percent sensitivity, 48 percent specificity, and a negative predictive value of 99 percent. With this threshold, a biopsy would be indicated in more than half the women, only 4 percent of whom had serious disease. Transvaginal ultrasonography has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease in asymptomatic postmenopausal women.

Journal of the American Geriatrics Society, 2010

OBJECTIVES-To determine if body weight (BMI) is independently associated with cognitive function ... more OBJECTIVES-To determine if body weight (BMI) is independently associated with cognitive function in postmenopausal women and the relationship between body fat distribution as estimated by waist-hip-ratio (WHR) and cognitive function.

Journal of the American Geriatrics Society, 2010

Objectives-Conjugated equine estrogen (CEE) therapies when initiated among older women have been ... more Objectives-Conjugated equine estrogen (CEE) therapies when initiated among older women have been shown to produce small decrements in global cognitive function. We are interested whether these persist after cessation and extend to specific cognitive domains.

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2011

Background. Muscle weakness and obesity are two significant threats to mobility facing the increa... more Background. Muscle weakness and obesity are two significant threats to mobility facing the increasing number of older adults. To date, there are no studies that have examined the association of strength and body mass index (BMI) on event rates on a widely used performance measure of major mobility disability.

Journal of Geriatric Psychiatry and Neurology, 2014

Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and prob... more Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N ¼ 204) and without (N ¼ 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline.

Journal of Dental Research, 1988

Recent evidence has suggested that the cariostatic effects of topical fluoride (F) are related to... more Recent evidence has suggested that the cariostatic effects of topical fluoride (F) are related to the presence of low concentrations of ionic F in the oral environment. The purpose of this study was to compare the retention of F in the oral environment over 24-hour periods after the use of a F dentifrice or a F rinse. Groups of ten consenting adult subjects (age 18-52 years) brushed and/or rinsed (B/R) in a standardized manner twice per day in the morning (AM) and before bed (PM) with either a placebo dentifrice (8 ppm F), NaF dentifrice (1100 ppm F), or NaF rinse (225 ppm F). Experiments were performed with placebo dentifrice only (PD); F dentifrice only (FD); F dentifrice followed by F rinse (FD/FR); placebo dentifrice followed by F rinse (PD/FR); and F rinse followed by placebo dentifrice (FR/PD). Unstimulated whole saliva samples were collected at baseline and then at 0, 15, 30, and 45 min, 1, 2, and 8 hr after B/R in the AM, after B/R in the PM and upon rising the following morning. Salivary flow rate and F were determined for each sampling interval. The results of this study suggest that: (1) F rinse may be a more effective way of delivering topical F than F dentifrice; (2) based on F retention, the combination of FD/FR was not more effective than FR only (PD/FR); (3) older individuals with gingival recession retained higher F levels; and (4) bedtime F application resulted in longer F retention than did daytime application, which may have important implications for enamel remineralization.

Journal of Affective Disorders, 2011

Objective-Late-life depressive symptoms (DS) increase the risk of incident mild cognitive impairm... more Objective-Late-life depressive symptoms (DS) increase the risk of incident mild cognitive impairment and probable dementia in the elderly. Our objectives were to examine the relationship between elevated DS and regional brain volumes including frontal lobe subregions, hippocampus and amygdala, and to determine whether elevated DS were associated with increased subclinical cerebrovascular disease in postmenopausal women.

JAMA, 2003

for the WHIMS Investigators D ECLINING COGNITIVE FUNCtion is a growing public health concern for ... more for the WHIMS Investigators D ECLINING COGNITIVE FUNCtion is a growing public health concern for older adults, given the welldocumented pattern of age-associated decrements in many areas of cognitive performance 1 and the increasing proportion of elderly individuals in the US population. The prevalence of ageassociated memory impairment in the general older population is estimated to be between 17% and 34%. 2-4 In postmenopausal women, the effect of reduced sex hormones, especially estrogen and progesterone, on cognitive decline is of particular interest because of their modulating effects on Context Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women.

International Journal of Gynecology & Obstetrics, 1996

International Journal of Geriatric Psychiatry, 2013

Computer-administered assessment of cognitive function is being increasingly incorporated in clin... more Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials; however, its performance in these settings has not been systematically evaluated. The Seniors Health and Activity Research Program pilot trial (N = 73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Elders investigators incorporated this battery in a full-scale multicenter clinical trial (N = 1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intraclass correlations [ICC]). Computer-based assessments of cognitive function had consistent relationships across the pilot and full-scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the Lifestyle Interventions and Independence for Elders cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (>83%) were achieved on all computer-based measures; however, rates of missing data were higher among older participants (odds ratio = 1.06 for each additional year; p < 0.001) and those who reported no current computer use (odds ratio = 2.71; p < 0.001). ICCs among clinics were at least as low (ICC < 0.013) as for interviewer measures (ICC < 0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance. Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals.

Diabetes Care, 2009

OBJECTIVE -To determine the prevalence and risk factors for urinary incontinence among different ... more OBJECTIVE -To determine the prevalence and risk factors for urinary incontinence among different racial/ethnic groups of overweight and obese women with type 2 diabetes. RESEARCH DESIGN AND METHODS -Cross-sectional analysis of baseline data from the Action for Health in Diabetes (Look AHEAD) study, a randomized clinical trial with 2,994 overweight/obese women with type 2 diabetes. RESULTS -Weekly incontinence (27%) was reported more often than other diabetesassociated complications, including retinopathy (7.5%), microalbuminuria (2.2%), and neuropathy (1.5%). The prevalence of weekly incontinence was highest among non-Hispanic whites (32%) and lowest among African Americans (18%), and Asians (12%) (P Ͻ 0.001). Asian and African American women had lower odds of weekly incontinence compared with non-Hispanic whites (75 and 55% lower, respectively; P Ͻ 0.001). Women with a BMI of Ն35 kg/m 2 had a higher odds of overall and stress incontinence (55-85% higher; P Ͻ 0.03) compared with that for nonobese women. Risk factors for overall incontinence, as well as for stress and urgency incontinence, included prior hysterectomy (40 -80% increased risk; P Ͻ 0.01) and urinary tract infection in the prior year (55-90% increased risk; P Ͻ 0.001). CONCLUSIONS -Among overweight and obese women with type 2 diabetes, urinary incontinence is highly prevalent and far exceeds the prevalence of other diabetes complications. Racial/ethnic differences in incontinence prevalence are similar to those in women without diabetes, affecting non-Hispanic whites more than Asians and African Americans. Increasing obesity (BMI Ն35 kg/m 2 ) was the strongest modifiable risk factor for overall incontinence and stress incontinence in this diverse cohort.

Controlled Clinical Trials, 1998

Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that ... more Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Women’s Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65

Atherosclerosis, 2003

Purpose: To characterize the intercorrelation of changes in intimal-medial thickness (IMT) among ... more Purpose: To characterize the intercorrelation of changes in intimal-medial thickness (IMT) among carotid artery sites and examine the influence of diabetes and sex on these correlations. Methods: Ultrasonographic IMT measurements from the near and far walls of common and internal segments in the arteries of 1207 participants of the Insulin Resistance Atherosclerosis Study (IRAS) were analyzed to estimate the underlying correlations of IMT changes (average of 5.2 years) among artery sites after correction for measurement error. Results: Differences in IMT progression associated with diabetes and sex were evident at all sites. IMT changes were strongly correlated between left and right arteries (r = 0.32-0.73) and near and far walls (r = 0.42-0.87). Correlations of IMT changes at corresponding sites of internal versus common segments were reduced from r = 0.32 among normal individuals to r = 0.09 among those with diabetes, but were similar for women and men. Conclusions: IMT progression is a diffuse process involving all carotid artery sites. Diabetes does not influence the bilateral and radial nature of progression, but reduces the correlation between distal sites within an artery. Pooling measurements across arteries and walls often yields the most efficient analyses.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2003

Objective-We sought to determine the rate of progression of carotid atherosclerosis in persons wi... more Objective-We sought to determine the rate of progression of carotid atherosclerosis in persons with normal glucose tolerance, impaired glucose tolerance, and undiagnosed and diagnosed type 2 diabetes. Methods and Results-The Insulin Resistance Atherosclerosis Study (IRAS) is an observational cohort study in which 1192 men and women were examined at a 5-year interval. Participants of 3 ethnic groups (non-Hispanic white, African American, and Hispanic) were selected from the general population to represent a range of glucose tolerance. Baseline and follow-up ultrasound studies were obtained to estimate progression of common carotid artery (CCA) and internal carotid artery (ICA) intimal-medial thickness (IMT). Baseline glucose tolerance status was defined by an oral glucose tolerance test and World Health Organization criteria. In persons with normal glucose tolerance, progression of CCA IMT was 3.8 m/y, and ICA IMT, 17.7 m/y. In both CCA and ICA, progression of IMT, unadjusted for cardiovascular disease (CVD) risk factors, was approximately twice the rate in persons with diabetes than in those with normal or impaired glucose tolerance. Adjustment for CVD risk factors attenuated these differences somewhat in both sites of the carotid artery. Persons with undiagnosed diabetes had a greater ICA IMT progression rate than did persons with diagnosed diabetes (33.9 m/y vs 26.6 m/y, PϭNS). Progression rates did not differ between persons with normal and impaired glucose tolerance.

Annals of Epidemiology, 2007

PURPOSE: Our study aim was to identify factors that may contribute to the racial disparity in pre... more PURPOSE: Our study aim was to identify factors that may contribute to the racial disparity in pregnancyrelated mortality. METHODS: We examined differences in severity of disease, comorbidities, and receipt of care among 608 (304 African-American and 304 white) consecutive patients of non-Hispanic ethnicity with one of three pregnancy-related morbidities (pregnancy-related hypertension, puerperal infection, and hemorrhage) from hospitals selected at random from a statewide region. RESULTS: African-American women had more severe hypertension, lower hemoglobin concentrations preceding hemorrhage, more antepartum hospital admissions, and a higher rate of obesity. The rate of surgical intervention for hemorrhage was lower among African-Americans, although the severity of hemorrhage did not differ between the two racial groups. More African-American women received eclampsia prophylaxis. After stratifying by severity of hypertension, we found that more African-Americans received antihypertensive therapy. The rate of enrollment for prenatal care was lower in the African-American group. Among women receiving prenatal care, African-American women enrolled significantly later in their pregnancies. CONCLUSIONS: We have identified racial differences in severity of disease, comorbidities, and care status among women with pregnancy-related complications that would place African-Americans at disadvantage to survive pregnancy. These differences are potentially modifiable.

Alzheimers & Dementia, Jul 1, 2014

Background: Spatial gradients in cortical thinning are a hallmark of dementias, and are shown to ... more Background: Spatial gradients in cortical thinning are a hallmark of dementias, and are shown to follow stereotypical patterns specific to each dementia. The signature of the disease is muchmore clearly visible in cortical thickness gradients taken between different brain regions, for example anterior-posterior gradients in AD as AD is known to affect the posterior cortices such as the medial temporal lobes, the precuneus etc. preferentially and early in the course of the disease. Keeping this idea of preferential gradient is mind, We reformulate our previously developed novel imaging cortical biomarker based on graph-theoretic analysis of inter-regional covariance of cortical thickness, called ThickNet features [1] to develop novel covariance features based on dissimilarity in thickness. These features capture the spatial thickness gradients within each subject. We call them Dissimilarity based Extraction of Covariance LInked NEtwork (DECLINE) features.We show that they outperform ThickNet features for the early detection of Alzheimer’s disease. DECLINE features are first of its kind and show promise in detecting the cognitive decline predictive of AD.Methods: Cortical thickness is extracted from the MRI scan using the method [2] for each patient and the features are registered to a common atlas surface to establish vertex-wise correspondence. Then the cortex of each patient is partitioned into large number (e.g. K1⁄4300 vertices per patch) of small areas by k-means clustering of vertices spatially on the atlas surface (Figure 1). A graph is then constructed by establishing a link between two such patches if dissimilarity (abs. difference inmean-thickness) in thickness is above a given threshold (e.g. 0.5mm). From this binary undirected graph, we compute several graph-theoretic properties called DECLINE features to represent each patient (See Figure 2), namely nodal degree, betweenness centrality and clustering coefficient. Using the same ADNI dataset on which we demonstrated the diagnostic utility of ThickNet features, we show that DECLINE features outperform ThickNet features, and show potential for the early detection of Alzheimer’s disease. Results: Using our Repeated Holdout, Stratified Training set (RHsT) cross-validation method proposed in [1] (See Figure 3), DECLINE features produced an area under ROC (AUC) of 0.93 in discriminating AD from healthy controls (CN), and an AUC of 0.87 in discriminating MCI converters (MCIc) from CN. The results presented in Figure 4 show DECLINE features significantly outperform ThickNet features in all the experiments. Conclusions: We present novel DECLINE measures based on inter-regional covariance of cortical thickness from structural MRI and demonstrate their performance on a benchmark ADNI dataset for early detection of Alzheimer’s disease.

Journal of the American Heart Association, Jan 2, 2017

Data are sparse regarding the value of physical activity (PA) surveillance among older adults-par... more Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). A...

Ageing Research Reviews, 2018

Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying... more Growing evidence suggests chronic low-grade inflammation (LGI) as a possible mechanism underlying the aging process. Some biological and pharmaceutical compounds may reduce systemic inflammation and potentially avert functional decline occurring with aging. The aim of the present meta-analysis was to examine the association of pre-selected interventions on two established biomarkers of inflammation, interleukin-6 (IL-6), and C-reactive protein (CRP) in middle-age and older adults with chronic LGI. We reviewed the literature on potential anti-inflammatory compounds, selecting them based on safety, tolerability, acceptability, innovation, affordability, and evidence from randomized controlled trials. Six compounds met all five inclusion criteria for our systematic review and meta

Stroke, 1999

Background and Purpose-It is generally assumed that risk factors affect extracranial carotid inti... more Background and Purpose-It is generally assumed that risk factors affect extracranial carotid intimal-medial thickness similarly among all arterial segments. This assumption underlies use of single segments or walls of segments as outcome variables for risk factor studies and clinical trials. However, if the impact of risk factors was unequal for various segments or circumferentially asymmetrical within segments, then inferences drawn from a single segment or wall might not be generalizable; furthermore, since individual segments and walls have unique histological characteristics and are differentially exposed to turbulent flow, risk factor relationships with a particular segment or wall may provide inferences regarding pathogenesis of atherosclerosis. Methods-We evaluated associations of risk factors with intimal-medial thickness at the near and far walls of the common carotid artery, bifurcation, and internal carotid artery in 280 individuals older than 45 years equally divided between coronary artery disease cases and controls and between men and women. Results-The patterns of differences in mean intimal-medial thickness among segments vary, depending on age, history of hypertension, body mass index in women, and coronary (case-control) status. The asymmetry of disease depended on blood glucose concentrations, prior history of diabetes, smoking, and coronary status. Sex, postmenopausal status, LDL cholesterol, systolic blood pressure, and history of myocardial infarction all had statistically significant relationships with intimal-medial thickness that were fairly homogeneous among arterial sites.

New England Journal of Medicine, 1997

Transvaginal ultrasonography is a noninvasive procedure that may be used to detect endometrial di... more Transvaginal ultrasonography is a noninvasive procedure that may be used to detect endometrial disease. However, its usefulness in screening for asymptomatic disease in postmenopausal women before or during treatment with estrogen or estrogen-progesterone replacement is not known. We compared the sensitivity and specificity of transvaginal ultrasonography and endometrial biopsy for the detection of endometrial disease in 448 postmenopausal women who received estrogen alone, cyclic or continuous estrogen-progesterone, or placebo for three years. Concurrent ultrasonographic and biopsy results were available for 577 examinations in the 448 women, 99 percent of whom were undergoing routine annual follow-up. Endometrial thickness was less than 5 mm in 45 percent of the examinations, 5 to 10 mm in 41 percent, more than 10 mm in 12 percent, and not measured in 2 percent, and it was higher in the women receiving estrogen alone than in the other groups. Biopsy detected 11 cases of serious disease: 1 case of adenocarcinoma, 2 cases of atypical simple hyperplasia, and 8 cases of complex hyperplasia. Biopsy also detected simple hyperplasia in 20 cases. At a threshold value of 5 mm for endometrial thickness, transvaginal ultrasonography had a positive predictive value of 9 percent for detecting any abnormality, with 90 percent sensitivity, 48 percent specificity, and a negative predictive value of 99 percent. With this threshold, a biopsy would be indicated in more than half the women, only 4 percent of whom had serious disease. Transvaginal ultrasonography has a poor positive predictive value but a high negative predictive value for detecting serious endometrial disease in asymptomatic postmenopausal women.

Journal of the American Geriatrics Society, 2010

OBJECTIVES-To determine if body weight (BMI) is independently associated with cognitive function ... more OBJECTIVES-To determine if body weight (BMI) is independently associated with cognitive function in postmenopausal women and the relationship between body fat distribution as estimated by waist-hip-ratio (WHR) and cognitive function.

Journal of the American Geriatrics Society, 2010

Objectives-Conjugated equine estrogen (CEE) therapies when initiated among older women have been ... more Objectives-Conjugated equine estrogen (CEE) therapies when initiated among older women have been shown to produce small decrements in global cognitive function. We are interested whether these persist after cessation and extend to specific cognitive domains.

The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2011

Background. Muscle weakness and obesity are two significant threats to mobility facing the increa... more Background. Muscle weakness and obesity are two significant threats to mobility facing the increasing number of older adults. To date, there are no studies that have examined the association of strength and body mass index (BMI) on event rates on a widely used performance measure of major mobility disability.

Journal of Geriatric Psychiatry and Neurology, 2014

Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and prob... more Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N ¼ 204) and without (N ¼ 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline.

Journal of Dental Research, 1988

Recent evidence has suggested that the cariostatic effects of topical fluoride (F) are related to... more Recent evidence has suggested that the cariostatic effects of topical fluoride (F) are related to the presence of low concentrations of ionic F in the oral environment. The purpose of this study was to compare the retention of F in the oral environment over 24-hour periods after the use of a F dentifrice or a F rinse. Groups of ten consenting adult subjects (age 18-52 years) brushed and/or rinsed (B/R) in a standardized manner twice per day in the morning (AM) and before bed (PM) with either a placebo dentifrice (8 ppm F), NaF dentifrice (1100 ppm F), or NaF rinse (225 ppm F). Experiments were performed with placebo dentifrice only (PD); F dentifrice only (FD); F dentifrice followed by F rinse (FD/FR); placebo dentifrice followed by F rinse (PD/FR); and F rinse followed by placebo dentifrice (FR/PD). Unstimulated whole saliva samples were collected at baseline and then at 0, 15, 30, and 45 min, 1, 2, and 8 hr after B/R in the AM, after B/R in the PM and upon rising the following morning. Salivary flow rate and F were determined for each sampling interval. The results of this study suggest that: (1) F rinse may be a more effective way of delivering topical F than F dentifrice; (2) based on F retention, the combination of FD/FR was not more effective than FR only (PD/FR); (3) older individuals with gingival recession retained higher F levels; and (4) bedtime F application resulted in longer F retention than did daytime application, which may have important implications for enamel remineralization.

Journal of Affective Disorders, 2011

Objective-Late-life depressive symptoms (DS) increase the risk of incident mild cognitive impairm... more Objective-Late-life depressive symptoms (DS) increase the risk of incident mild cognitive impairment and probable dementia in the elderly. Our objectives were to examine the relationship between elevated DS and regional brain volumes including frontal lobe subregions, hippocampus and amygdala, and to determine whether elevated DS were associated with increased subclinical cerebrovascular disease in postmenopausal women.

JAMA, 2003

for the WHIMS Investigators D ECLINING COGNITIVE FUNCtion is a growing public health concern for ... more for the WHIMS Investigators D ECLINING COGNITIVE FUNCtion is a growing public health concern for older adults, given the welldocumented pattern of age-associated decrements in many areas of cognitive performance 1 and the increasing proportion of elderly individuals in the US population. The prevalence of ageassociated memory impairment in the general older population is estimated to be between 17% and 34%. 2-4 In postmenopausal women, the effect of reduced sex hormones, especially estrogen and progesterone, on cognitive decline is of particular interest because of their modulating effects on Context Observational studies have suggested that postmenopausal hormone treatment may improve cognitive function, but data from randomized clinical trials have been sparse and inconclusive. The Women's Health Initiative Memory Study (WHIMS) is an ancillary study of the Women's Health Initiative (WHI) hormone therapy trials. On July 8, 2002, the estrogen plus progestin therapy in the WHI trial was discontinued because of certain increased health risks for women.

International Journal of Gynecology & Obstetrics, 1996

International Journal of Geriatric Psychiatry, 2013

Computer-administered assessment of cognitive function is being increasingly incorporated in clin... more Computer-administered assessment of cognitive function is being increasingly incorporated in clinical trials; however, its performance in these settings has not been systematically evaluated. The Seniors Health and Activity Research Program pilot trial (N = 73) developed a computer-based tool for assessing memory performance and executive functioning. The Lifestyle Interventions and Independence for Elders investigators incorporated this battery in a full-scale multicenter clinical trial (N = 1635). We describe relationships that test scores have with those from interviewer-administered cognitive function tests and risk factors for cognitive deficits and describe performance measures (completeness, intraclass correlations [ICC]). Computer-based assessments of cognitive function had consistent relationships across the pilot and full-scale trial cohorts with interviewer-administered assessments of cognitive function, age, and a measure of physical function. In the Lifestyle Interventions and Independence for Elders cohort, their external validity was further demonstrated by associations with other risk factors for cognitive dysfunction: education, hypertension, diabetes, and physical function. Acceptable levels of data completeness (>83%) were achieved on all computer-based measures; however, rates of missing data were higher among older participants (odds ratio = 1.06 for each additional year; p < 0.001) and those who reported no current computer use (odds ratio = 2.71; p < 0.001). ICCs among clinics were at least as low (ICC < 0.013) as for interviewer measures (ICC < 0.023), reflecting good standardization. All cognitive measures loaded onto the first principal component (global cognitive function), which accounted for 40% of the overall variance. Our results support the use of computer-based tools for assessing cognitive function in multicenter clinical trials of older individuals.

Diabetes Care, 2009

OBJECTIVE -To determine the prevalence and risk factors for urinary incontinence among different ... more OBJECTIVE -To determine the prevalence and risk factors for urinary incontinence among different racial/ethnic groups of overweight and obese women with type 2 diabetes. RESEARCH DESIGN AND METHODS -Cross-sectional analysis of baseline data from the Action for Health in Diabetes (Look AHEAD) study, a randomized clinical trial with 2,994 overweight/obese women with type 2 diabetes. RESULTS -Weekly incontinence (27%) was reported more often than other diabetesassociated complications, including retinopathy (7.5%), microalbuminuria (2.2%), and neuropathy (1.5%). The prevalence of weekly incontinence was highest among non-Hispanic whites (32%) and lowest among African Americans (18%), and Asians (12%) (P Ͻ 0.001). Asian and African American women had lower odds of weekly incontinence compared with non-Hispanic whites (75 and 55% lower, respectively; P Ͻ 0.001). Women with a BMI of Ն35 kg/m 2 had a higher odds of overall and stress incontinence (55-85% higher; P Ͻ 0.03) compared with that for nonobese women. Risk factors for overall incontinence, as well as for stress and urgency incontinence, included prior hysterectomy (40 -80% increased risk; P Ͻ 0.01) and urinary tract infection in the prior year (55-90% increased risk; P Ͻ 0.001). CONCLUSIONS -Among overweight and obese women with type 2 diabetes, urinary incontinence is highly prevalent and far exceeds the prevalence of other diabetes complications. Racial/ethnic differences in incontinence prevalence are similar to those in women without diabetes, affecting non-Hispanic whites more than Asians and African Americans. Increasing obesity (BMI Ն35 kg/m 2 ) was the strongest modifiable risk factor for overall incontinence and stress incontinence in this diverse cohort.

Controlled Clinical Trials, 1998

Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that ... more Evidence from animal, human cross-sectional, case-control, and prospective studies indicate that hormone replacement therapy (HRT) is a promising treatment to delay the onset of symptoms of dementia. The Women’s Health Initiative Memory Study (WHIMS) is the first double-masked, randomized, placebo-controlled, long-term clinical trial designed to test the hypothesis that HRT reduces the incidence of all-cause dementia in women aged 65

Atherosclerosis, 2003

Purpose: To characterize the intercorrelation of changes in intimal-medial thickness (IMT) among ... more Purpose: To characterize the intercorrelation of changes in intimal-medial thickness (IMT) among carotid artery sites and examine the influence of diabetes and sex on these correlations. Methods: Ultrasonographic IMT measurements from the near and far walls of common and internal segments in the arteries of 1207 participants of the Insulin Resistance Atherosclerosis Study (IRAS) were analyzed to estimate the underlying correlations of IMT changes (average of 5.2 years) among artery sites after correction for measurement error. Results: Differences in IMT progression associated with diabetes and sex were evident at all sites. IMT changes were strongly correlated between left and right arteries (r = 0.32-0.73) and near and far walls (r = 0.42-0.87). Correlations of IMT changes at corresponding sites of internal versus common segments were reduced from r = 0.32 among normal individuals to r = 0.09 among those with diabetes, but were similar for women and men. Conclusions: IMT progression is a diffuse process involving all carotid artery sites. Diabetes does not influence the bilateral and radial nature of progression, but reduces the correlation between distal sites within an artery. Pooling measurements across arteries and walls often yields the most efficient analyses.

Arteriosclerosis, Thrombosis, and Vascular Biology, 2003

Objective-We sought to determine the rate of progression of carotid atherosclerosis in persons wi... more Objective-We sought to determine the rate of progression of carotid atherosclerosis in persons with normal glucose tolerance, impaired glucose tolerance, and undiagnosed and diagnosed type 2 diabetes. Methods and Results-The Insulin Resistance Atherosclerosis Study (IRAS) is an observational cohort study in which 1192 men and women were examined at a 5-year interval. Participants of 3 ethnic groups (non-Hispanic white, African American, and Hispanic) were selected from the general population to represent a range of glucose tolerance. Baseline and follow-up ultrasound studies were obtained to estimate progression of common carotid artery (CCA) and internal carotid artery (ICA) intimal-medial thickness (IMT). Baseline glucose tolerance status was defined by an oral glucose tolerance test and World Health Organization criteria. In persons with normal glucose tolerance, progression of CCA IMT was 3.8 m/y, and ICA IMT, 17.7 m/y. In both CCA and ICA, progression of IMT, unadjusted for cardiovascular disease (CVD) risk factors, was approximately twice the rate in persons with diabetes than in those with normal or impaired glucose tolerance. Adjustment for CVD risk factors attenuated these differences somewhat in both sites of the carotid artery. Persons with undiagnosed diabetes had a greater ICA IMT progression rate than did persons with diagnosed diabetes (33.9 m/y vs 26.6 m/y, PϭNS). Progression rates did not differ between persons with normal and impaired glucose tolerance.

Annals of Epidemiology, 2007

PURPOSE: Our study aim was to identify factors that may contribute to the racial disparity in pre... more PURPOSE: Our study aim was to identify factors that may contribute to the racial disparity in pregnancyrelated mortality. METHODS: We examined differences in severity of disease, comorbidities, and receipt of care among 608 (304 African-American and 304 white) consecutive patients of non-Hispanic ethnicity with one of three pregnancy-related morbidities (pregnancy-related hypertension, puerperal infection, and hemorrhage) from hospitals selected at random from a statewide region. RESULTS: African-American women had more severe hypertension, lower hemoglobin concentrations preceding hemorrhage, more antepartum hospital admissions, and a higher rate of obesity. The rate of surgical intervention for hemorrhage was lower among African-Americans, although the severity of hemorrhage did not differ between the two racial groups. More African-American women received eclampsia prophylaxis. After stratifying by severity of hypertension, we found that more African-Americans received antihypertensive therapy. The rate of enrollment for prenatal care was lower in the African-American group. Among women receiving prenatal care, African-American women enrolled significantly later in their pregnancies. CONCLUSIONS: We have identified racial differences in severity of disease, comorbidities, and care status among women with pregnancy-related complications that would place African-Americans at disadvantage to survive pregnancy. These differences are potentially modifiable.