Mark A Espeland

Wake Forest School of Medicine, Winston-Salem, North Carolina, United States

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Publications (269)1259.06 Total impact

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    ABSTRACT: Objective Ankle-brachial index (ABI) and interartery systolic blood pressure differences, as markers of vascular disease, are plausible risk factors for deficits in cognitive function among overweight and obese adults with type 2 diabetes.Methods The ABI and maximum interartery differences (MIAD) in systolic blood pressures were assessed annually for five years among 479 participants assigned to the control condition in a randomized clinical trial of a behavioral weight loss intervention. A battery of standardized cognitive function tests was administered 4 to 5 years later. Analyses of covariance were used to assess relationships that ABI, MIAD, and progression of ABI and MIAD had with cognitive function.ResultsThere was a curvilinear relationship between ABI and a composite index of cognitive function (p = 0.03), with lower ABI being associated with poorer function. In graded fashions, both greater MIAD and increases in MIAD over time also had modest relationships with poorer verbal memory (both p ≤ 0.05), processing speed (both p ≤ 0.05), and composite cognitive function (both p < 0.04). These relationships were independent of each other and remained evident after extensive covariate adjustment.Conclusions In overweight and obese adults with type 2 diabetes, lower ABI and larger interartery systolic blood pressure differences have modest, independent, graded relationships with poorer cognitive function 4–5 years later. Copyright © 2014 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 12/2014; · 3.09 Impact Factor
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    ABSTRACT: We investigated (a) cross-sectional associations between cognitive activity, cognitive performance, and MRI measures and (b) longitudinal associations between cognitive activity and change in cognitive performance, using structural equation modeling (SEM).
    The Journals of Gerontology Series B Psychological Sciences and Social Sciences 09/2014; · 3.01 Impact Factor
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    ABSTRACT: To assess the relative impact of an intensive lifestyle intervention (ILI) on use and costs of health care within the Look AHEAD trial.
    Diabetes care. 09/2014; 37(9):2548-56.
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    ABSTRACT: Young adulthood (age 18 to 35) is a high-risk period for unhealthy weight gain. Few studies have recruited for prevention of weight gain, particularly in young adults. This paper describes the recruitment protocol used in the Study of Novel Approaches to Prevention (SNAP).
    Trials 08/2014; 15(1):326. · 2.12 Impact Factor
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    ABSTRACT: The purpose of this study is to determine if the cumulative effects of head impacts from a season of high school football produce magnetic resonance imaging (MRI) measureable changes in the brain in the absence of clinically diagnosed concussion. Players from a local high school football team were instrumented with the Head Impact Telemetry System (HITs) during all practices and games. All players received pre- and post-season MRI, including diffusion tensor imaging (DTI). Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) was also conducted. Total impacts and Risk Weighted cumulative Exposure (RWE), including linear (RWELinear), rotational (RWERotational), and combined components (RWECP) were computed from the sensor data. Fractional, linear, planar and spherical anisotropies (FA, CL, CP, CS, respectively), as well as mean diffusivity (MD), were used to determine total number of abnormal white matter voxels defined as 2 standard deviations above or below the group mean. Delta (post-pre season) ImPACT scores for each individual were computed and compared to the DTI measures using the Spearman's rank correlation coefficient. None of the players analyzed experienced clinical concussion (N = 24). Regression analysis revealed a statistically significant linear relationship between RWECP and FA. Secondary analyses demonstrated additional statistically significant linear associations between RWE (RWECP and RWELinear) and all DTI measures. There was also a strong correlation between DTI measures and change in Verbal Memory subscore of the ImPACT. We demonstrate that a single season of football can produce brain MRI changes in the absence of clinical concussion. Similar brain MRI changes have been previously associated with mild traumatic brain injury.
    Journal of neurotrauma 05/2014; · 4.25 Impact Factor
  • R.R. Wing, T. Leahey, M. Espeland
    Obesity 05/2014; · 4.39 Impact Factor
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    ABSTRACT: It is unknown whether intentional weight loss provides long-term benefits for cognitive function. An ancillary study to a randomized controlled clinical trial was conducted in overweight and obese individuals (N = 978), aged 45-76 years at enrollment, with type 2 diabetes. An intensive behavioral intervention designed to promote and maintain weight loss through caloric restriction and increased physical activity was compared with diabetes support and education. Standardized assessments of cognitive function were collected an average of 8.1 years after trial enrollment. Participants assigned to intensive lifestyle intervention lost a mean (SE) 11.1% (0.4%) and 7.2% (0.5%) of weight at Years 1 and 8, respectively, compared with 1.0% (0.2%) and 3.3% (0.5%) in the control group (p < .001). Covariate-adjusted mean composite cognitive function test scores were similar for the two groups (p = .69), and no significant differences were found for any individual cognitive test. There was some evidence of a differential effect (nominal interaction p = .008) for a prespecified comparison: Intensive lifestyle intervention was associated with a relative mean benefit for composite cognitive function of 0.276 (95% confidence interval: 0.033, 0.520) SDs among individuals with body mass index less than 30kg/m(2) at baseline compared with a relative mean deficit of 0.086 (-0.021, 0.194) SDs among individuals with body mass more than or equal to 30kg/m(2). Eight years of intensive lifestyle intervention did not alter cognitive function in obese adults with type 2 diabetes; however, there was evidence for benefit among overweight but not obese individuals. Changes in cognition were not assessed in this cross-sectional study.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2014; · 4.31 Impact Factor
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    ABSTRACT: Objective Weight loss programs are often conducted in a group format, but it is unclear whether weight losses or adherence cluster within treatment group and whether characteristics of the group (e.g., size or homogeneity) affect outcomes. We examined these questions within Look AHEAD, a multicenter study of the effects of an intensive lifestyle intervention (ILI) in overweight/obese individuals with type 2 diabetes. Methods Weight losses and adherence (attendance, use of meal replacement products, and minutes of activity) were examined over one year of intervention in 2329 ILI participants in 209 treatment groups, which all received the same weight loss program. ResultsWeight losses did not cluster among members of a treatment group (intra-class correlation [ICC] of 0.007), whereas measures of adherence had small/moderate clustering (ICCs of 0.05-0.11). The 209 groups varied in weight losses, with a mean of 8.64% (SD = 2.35%, interquartile range = 6.82%, 10.32%), but neither size nor baseline homogeneity of members affected the outcome. Conclusions Although these findings suggest that it may not be necessary to control for clustering in behavioral weight loss studies, they also indicate that merely treating individuals in groups is not sufficient to harness social influences on weight loss.
    Obesity 03/2014; 22(3). · 4.39 Impact Factor
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    ABSTRACT: 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 = 204) and without (N = 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 Geriatric Psychiatry and Neurology 02/2014; · 1.63 Impact Factor
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    ABSTRACT: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88). Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.
    Neurology 02/2014; 82(5):427-34. · 8.30 Impact Factor
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    ABSTRACT: To test whether red blood cell (RBC) levels of marine omega-3 fatty acids measured in the Women's Health Initiative Memory Study were related to MRI brain volumes measured 8 years later. RBC eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and MRI brain volumes were assessed in 1,111 postmenopausal women from the Women's Health Initiative Memory Study. The endpoints were total brain volume and anatomical regions. Linear mixed models included multiple imputations of fatty acids and were adjusted for hormone therapy, time since randomization, demographics, intracranial volume, and cardiovascular disease risk factors. In fully adjusted models, a 1 SD greater RBC EPA + DHA (omega-3 index) level was correlated with 2.1 cm(3) larger brain volume (p = 0.048). DHA was marginally correlated (p = 0.063) with total brain volume while EPA was less so (p = 0.11). There were no correlations between ischemic lesion volumes and EPA, DHA, or EPA + DHA. A 1 SD greater omega-3 index was correlated with greater hippocampal volume (50 mm(3), p = 0.036) in fully adjusted models. Comparing the fourth quartile vs the first quartile of the omega-3 index confirmed greater hippocampal volume (159 mm(3), p = 0.034). A higher omega-3 index was correlated with larger total normal brain volume and hippocampal volume in postmenopausal women measured 8 years later. While normal aging results in overall brain atrophy, lower omega-3 index may signal increased risk of hippocampal atrophy. Future studies should examine whether maintaining higher RBC EPA + DHA levels slows the rate of hippocampal or overall brain atrophy.
    Neurology 01/2014; · 8.30 Impact Factor
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    ABSTRACT: Research has shown that several types of erythrocyte fatty acids (i.e., omega-3, omega-6, and trans) are associated with risk for cardiovascular diseases. However, there are complex metabolic and dietary relations among fatty acids, which induce correlations that are typically ignored when using them as risk predictors. A latent variable approach could summarize these complex relations into a few latent variable scores for use in statistical models. Twenty-two red blood cell (RBC) fatty acids were measured in Framingham (N = 3196). The correlation matrix of the fatty acids was modeled using structural equation modeling; the model was tested for goodness-of-fit and gender invariance. Thirteen fatty acids were summarized by three latent variables, and gender invariance was rejected so separate models were developed for men and women. A score was developed for the polyunsaturated fatty acid (PUFA) latent variable, which explained about 30% of the variance in the data. The PUFA score included loadings in opposing directions among three omega-3 and three omega-6 fatty acids, and incorporated the biosynthetic and dietary relations among them. Whether the PUFA factor score can improve the performance of risk prediction in cardiovascular diseases remains to be tested.
    Computational and Mathematical Methods in Medicine 01/2014; 2014:160520. · 1.02 Impact Factor
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    ABSTRACT: Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate-high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey-Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7) had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P<0.001). The LIFE Study will contribute important information on the effects of a structured physical activity program on cognitive outcomes in sedentary older adults at particular risk for mobility impairment. In addition to its importance in the area of prevention of cognitive decline, the LIFE Study will also likely serve as a model for exercise and other behavioral intervention trials in older adults.
    Clinical Interventions in Aging 01/2014; 9:1425-36. · 2.65 Impact Factor
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    ABSTRACT: We sought to determine the relationship between the omega-3 fatty acid content of red blood cell membranes (RBC), in particular docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), and baseline and new-onset depressive symptoms in post-menopausal women. We secondarily sought to characterize the association between dietary omega-3 fatty acid intake and depressive symptomatology. Study participants included 7086 members of the Women's Health Initiative Memory Study (aged 63-81 years) who had an assessment of RBC omega-3 fatty acid concentrations at the baseline screening visit. Depressive symptoms at baseline and follow-up were characterized using the Burnam eight-item scale for depressive disorders (Center for Epidemiologic Studies Depression Scale/Diagnostic Interview Schedule short form) and secondarily additionally inferred by antidepressant medication use. In multivariable-adjusted models, our primary exposure, RBC DHA + EPA, was not related to depressive symptoms by any measure at baseline or follow-up, nor were RBC total omega-3, DHA, or EPA (all p > 0.2). In contrast, dietary intake of omega-3 was positively associated with depressive symptoms at baseline (adjusted odds ratio 1.082, 95% confidence interval 1.004-1.166; p = 0.04 for dietary DHA + EPA and Burnam score ≥0.06), although this generally did not persist at follow-up. No relationship between RBC omega-3 levels and subsequent depressive symptoms was evident, and associations between dietary omega-3 and depressive symptoms were variable. Biomarkers of omega-3 status do not appear to be related to risk of new depression in post-menopausal women. Copyright © 2013 John Wiley & Sons, Ltd.
    International Journal of Geriatric Psychiatry 12/2013; · 3.09 Impact Factor
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    ABSTRACT: Little is known about the cognitive factors associated with adherence to anti-estrogen therapy. Our objective was to investigate the association between domain-specific cognitive function and adherence among women in a clinical prevention trial of oral anti-estrogen therapies. We performed a secondary analysis of Co-STAR, an ancillary study of the STAR breast cancer prevention trial in which postmenopausal women at increased breast cancer risk were randomized to tamoxifen or raloxifene. Co-STAR enrolled non-demented participants ≥65 years old to compare treatment effects on cognition. The cognitive battery assessed global cognitive function (Modified Mini-Mental State Exam), and specific cognitive domains of verbal knowledge, verbal fluency, figural memory, verbal memory, attention and working memory, spatial ability, and fine motor speed. Adherence was defined by a ratio of actual time taking therapy per protocol ≥80% of expected time. Logistic regression was used to evaluate the association between cognitive test scores and adherence to therapy. The mean age of the 1,331 Co-STAR participants was 67.2±4.3 years. Mean 3MS score was 95.1 (4.7) and 14% were non-adherent. In adjusted analyses, the odds of non-adherence were lower for those with better scores on verbal memory [OR (95% CI): 0.75 (0.62, 0.92)]. Larger relative deficits in verbal memory compared to verbal fluency were also associated with non-adherence [1.28(1.08, 1.51)]. Among non-demented older women, subtle differences in memory performance were associated with medication adherence. Differential performance across cognitive domains may help identify persons at greater risk for poor adherence.
    Cancer Prevention Research 11/2013; · 4.89 Impact Factor
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    ABSTRACT: The goal of this work is to introduce new metrics to assess risk of Alzheimer's disease (AD) which we call AD Pattern Similarity (AD-PS) scores. These metrics are the conditional probabilities modeled by large-scale regularized logistic regression. The AD-PS scores derived from structural MRI and cognitive test data were tested across different situations using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. The scores were computed across groups of participants stratified by cognitive status, age and functional status. Cox proportional hazards regression was used to evaluate associations with the distribution of conversion times from mild cognitive impairment to AD. The performances of classifiers developed using data from different types of brain tissue were systematically characterized across cognitive status groups. We also explored the performance of anatomical and cognitive-anatomical composite scores generated by combining the outputs of classifiers developed using different types of data. In addition, we provide the AD-PS scores performance relative to other metrics used in the field including the Spatial Pattern of Abnormalities for Recognition of Early AD (SPARE-AD) index and total hippocampal volume for the variables examined.
    PLoS ONE 11/2013; 8(11):e77949. · 3.53 Impact Factor
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    ABSTRACT: Objective: To assess whether weight loss improves markers of peripheral artery disease and vascular stenosis. Design and Methods: The Action for Health in Diabetes randomized clinical trial compared intensive lifestyle intervention (ILI) for weight loss to a control condition of diabetes support and education (DSE) in overweight or obese adults with type 2 diabetes. Annual ankle and brachial blood pressures over four years were used compute ankle-brachial indices (ABIs) and to assess inter-artery blood pressure differences in 5018 participants. Results: ILI, compared to DSE, produced 7.8% (Year 1) to 3.6% (Year 4) greater weight losses. These did not affect prevalence of low (<0.90) ABI (3.60% in DSE versus 3.14% in ILI; p=0.20) or elevated (>1.40) ABI (7.52% in DSE versus 7.59% in ILI: p=0.90), but produced smaller mean (SE) maximum inter-artery systolic blood pressure differences among ankle sites [19.7 (0.2) mmHg for ILI versus 20.6 (0.2) mmHg for DSE (p<0.001)] and between arms [5.8 (0.1) mmHg for ILI versus 6.1 (0.1) mmHg for DSE (p=0.01)]. Conclusions: Four years of intensive behavioral weight loss intervention did not significantly alter prevalence of abnormal ABI, however it did reduce differences in systolic blood pressures among arterial sites.
    Obesity 10/2013; · 4.39 Impact Factor
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    ABSTRACT: The prevalence and significance of low normal and abnormal ankle brachial index (ABI) values in a community-dwelling population of sedentary, older individuals is unknown. We describe the prevalence of categories of definite peripheral artery disease (PAD), borderline ABI, low normal ABI, and no PAD and their association with lower-extremity functional performance in the LIFE Study population. Participants age 70 to 89 in the LIFE Study underwent baseline measurement of the ABI, 400-m walk, and 4-m walking velocity. Participants were classified as follows: definite PAD (ABI <0.90), borderline PAD (ABI 0.90 to 0.99), low normal ABI (ABI 1.00 to 1.09), and no PAD (ABI 1.10 to 1.40). Of 1566 participants, 220 (14%) had definite PAD, 250 (16%) had borderline PAD, 509 (33%) had low normal ABI, and 587 (37%) had no PAD. Among those with definite PAD, 65% were asymptomatic. Adjusting for age, sex, race, body mass index, smoking, and comorbidities, lower ABI was associated with longer mean 400-m walk time: (definite PAD=533 seconds; borderline PAD=514 seconds; low normal ABI=503 seconds; and no PAD=498 seconds [P<0.001]). Among asymptomatic participants with and without PAD, lower ABI values were also associated with longer 400-m walk time (P<0.001) and slower walking velocity (P=0.042). Among older community-dwelling men and women, 14% had PAD and 49% had borderline or low normal ABI values. Lower ABI values were associated with greater functional impairment, suggesting that lower extremity atherosclerosis may be a common preventable cause of functional limitations in older people. http://clinicaltrials.gov/ Unique identifier: NCT01072500.
    Journal of the American Heart Association. 10/2013; 2(6):e000257.
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    ABSTRACT: To test the hypothesis that higher levels of red blood cell (RBC) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) have a protective association with domain-specific cognitive function in women aged 65 years and older. A total of 2,157 women with normal cognition enrolled in a clinical trial of postmenopausal hormone therapy were followed with annual cognitive testing for a median of 5.9 years. In this retrospective cohort study, we assessed the relationship between prerandomization RBC DHA + EPA levels and a) cognitive measures at baseline, and b) cognitive change over time. Endpoints were composite cognitive function and performance in 7 cognitive domains: fine motor speed, verbal memory, visual memory, spatial ability, verbal knowledge, verbal fluency, and working memory. After adjustment for demographic, clinical, and behavioral characteristics, no significant (p < 0.01) cross-sectional cognitive differences were found between women in the high and low DHA + EPA tertiles at the time of the first annual cognitive battery. In addition, no significant (p < 0.01) differences were found between the high and low DHA + EPA tertiles in the rate of cognitive change over time. We did not find an association between RBC DHA + EPA levels and age-associated cognitive decline in a cohort of older, dementia-free women.
    Neurology 09/2013; · 8.30 Impact Factor
  • JAMA Intern Med. 08/2013; 173(15):1429-1436.

Publication Stats

8k Citations
1,259.06 Total Impact Points

Institutions

  • 1994–2014
    • Wake Forest School of Medicine
      • • Department of Biostatistical Sciences
      • • Division of Public Health Sciences
      • • Department of Internal Medicine
      Winston-Salem, North Carolina, United States
  • 2013
    • Brown University
      Providence, Rhode Island, United States
  • 1991–2013
    • Wake Forest University
      • • Department of Biostatistical Sciences
      • • Department of Health and Exercise Science
      • • Department of Public Health Sciences
      • • School of Medicine
      Winston-Salem, North Carolina, United States
  • 2012
    • Sioux Falls Seminary
      Sioux Falls, South Dakota, United States
    • Medical College of Wisconsin
      • Department of Psychiatry and Behavioral Medicine
      Milwaukee, WI, United States
  • 2011
    • Tufts University
      Georgia, United States
    • Northwestern University
      • Department of Medicine
      Evanston, IL, United States
    • RAND Corporation
      Santa Monica, California, United States
  • 2004–2011
    • National Institute on Aging
      • Laboratory of Personality and Cognition (LPC)
      Baltimore, Maryland, United States
  • 2010
    • The National Institute of Diabetes and Digestive and Kidney Diseases
      Maryland, United States
  • 2008
    • The University of Tennessee Health Science Center
      • Department of Preventive Medicine
      Memphis, TN, United States
    • University of Washington Seattle
      • Department of Radiology
      Seattle, WA, United States
  • 2003
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 2002
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
  • 2000
    • London School of Hygiene and Tropical Medicine
      Londinium, England, United Kingdom
  • 1993
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1987–1991
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 1990
    • University of Leeds
      Leeds, England, United Kingdom
  • 1987–1990
    • University of Rochester
      Rochester, New York, United States
  • 1989
    • University Center Rochester
      • Department of Biostatistics
      Rochester, Minnesota, United States