Mark A Espeland

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

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Publications (242)1054.83 Total impact

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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). · 3.92 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; · 3.53 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; · 8.25 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; · 2.98 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: 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; · 8.25 Impact Factor
  • JAMA Intern Med. 08/2013; 173(15):1429-1436.
  • New England Journal of Medicine 06/2013; · 51.66 Impact Factor
  • Journal of the American Geriatrics Society 06/2013; 61(6):1050-1. · 3.98 Impact Factor
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    ABSTRACT: The aim of this study was to determine the effects of estrogen therapy (ET) on carotid artery inflammation when initiated early and late relative to surgical menopause. Female cynomolgus macaques consuming atherogenic diets were ovariectomized and randomized to control or oral estradiol (E2; human equivalent dose of 1 mg/d micronized E2) initiated at 1 month (early menopause, n = 24) or 54 months (late menopause, n = 40) after ovariectomy. The treatment period was 8 months. Carotid artery expression of the markers of monocyte/macrophages (CD68 and CD163), dendritic cells (CD83), natural killer cells (neural cell adhesion molecule-1), and interferon-γ was significantly lower in E2-treated animals in the early menopause group but not in the late menopause group (P < 0.05). In contrast, carotid artery transcripts for T-cell markers (CD3, CD4, CD8, and CD25), interleukin-10, type I collagen, monocyte chemoattractant protein-1, matrix metalloproteinase-9, and tumor necrosis factor-α were lower in E2-treated monkeys regardless of menopausal stage (P < 0.05). ET initiated soon after menopause inhibits macrophage accumulation in the carotid artery, an effect that is not observed when E2 is administered after several years of estrogen deficiency. No evidence for pro-inflammatory effects of late ET is observed. The results provide support for the timing hypothesis of postmenopausal ET with implications for the interpretation of outcomes in the Women's Health Initiative.
    Menopause (New York, N.Y.) 05/2013; 20(5):540-7. · 3.08 Impact Factor
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    ABSTRACT: The liver is an insulin-responsive organ that contributes significantly to both whole body insulin sensitivity and availability of sex steroids through the production of sex hormone binding globulin (SHBG). Our objective was to explore whether lower SHBG was associated with ectopic liver fat and mediated its effect on insulin resistance in The Study of Women's Health Across the Nation (SWAN). A subset of midlife African American and Caucasian women from SWAN (n = 208; 50.9 ± 0.18 yrs; 71% Caucasian) had computed tomography scans to quantify visceral, subcutaneous and liver fat. Blood samples were collected and assayed for hormonal and metabolic markers. The cohort, while overweight, was generally healthy, and both liver fat and SHBG were unaffected by menopausal stage or race. Both higher liver fat and lower SHBG levels were significantly associated with higher insulin concentrations after adjustment for adiposity (r = -0.25, P < 0.001 and r = -0.18, P = 0.01). SHBG and liver fat had additive effects on insulin concentrations such that women with the lowest SHBG and the highest fat levels had the highest values (interaction P = 0.09). The association between SHBG and insulin was more apparent among women with fattier livers. SHBG and liver fat appear to have independent effects on insulin levels as adjustment for each other did not diminish the strength of either association (P = 0.023 and 0.001 respectively). These results confirmed the strong independent associations between increased liver fat and decreased SHBG with increased metabolic risk in midlife women. Further these data underscore the need for additional research into the role of liver fat in modifying SHBG's influence on insulin levels.
    Obesity 05/2013; 21(5):1031-8. · 3.92 Impact Factor
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    ABSTRACT: BACKGROUND: Weight gain during young adulthood is common and is associated with increased cardiovascular risk. Preventing this weight gain from occurring may be critical to improving long-term health. Few studies have focused on weight gain prevention, and these studies have had limited success. SNAP (Study of Novel Approaches to Weight Gain Prevention) is an NIH-funded randomized clinical trial examining the efficacy of two novel self-regulation approaches to weight gain prevention in young adults compared to a minimal treatment control. The interventions focus on either small, consistent changes in eating and exercise behaviors, or larger, periodic changes to buffer against expected weight gains. METHODS: SNAP targets recruitment of six hundred young adults (18--35 years) with a body mass index between 23.0-30.0 kg/m2, who will be randomly assigned with equal probability to: (1) minimal intervention control; (2) self-regulation with Small Changes; or (3) self-regulation with Large Changes. Both interventions receive 8 weekly face-to-face group sessions, followed by 2 monthly sessions, with two 4-week refresher courses in subsequent years. Participants are instructed to report weight via web at least monthly thereafter, and receive monthly e-mail feedback. Participants in Small Changes are taught to make small daily changes (~100 calorie changes) in how much or what they eat and to accumulate 2000 additional steps per day. Participants in Large Changes are taught to create a weight loss buffer of 5--10 pounds once per year to protect against anticipated weight gains. Both groups are encouraged to self-weigh daily and taught a self-regulation color zone system that specifies action depending on weight gain prevention success. Individualized treatment contact is offered to participants who report weight gains. Participants are assessed at baseline, 4 months, and then annually. The primary outcome is weight gain over an average of 3 years of follow-up; secondary outcomes include diet and physical activity behaviors, psychosocial measures, and cardiovascular disease risk factors. DISCUSSION: SNAP is unique in its focus on weight gain prevention in young adulthood. The trial will provide important information about whether either or both of these novel interventions are effective in preventing weight gain. ( NCT 01183689)Trial registration: NCT 01183689.
    BMC Public Health 04/2013; 13(1):300. · 2.08 Impact Factor
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    ABSTRACT: BACKGROUND: After clinical trials end, continued follow-up of the assembled cohort often is desirable for additional research. Factors influencing participants' decisions to consent to additional follow-up and how these shape posttrial cohorts have not been broadly studied. PURPOSE: We examined how two re-enrollment campaigns and the passage of time altered features of the posttrial cohorts compared with the original Women's Health Initiative (WHI) Hormone Therapy clinical trials. METHODS: We examined associations that markers of sociodemography, health, lifestyle, and on-trial experiences had with re-enrollment and contrasted the characteristics of successive posttrial cohorts with those of the original enrollees. RESULTS: The posttrial enrollment campaigns re-enrolled 81.1% and 82.5% of available women, respectively. Women who re-enrolled tended to have better health characteristics than those not re-enrolled. Compared to women of comparable age in the original cohort, women retained for the second posttrial follow-up less often had a history of cardiovascular disease (odds ratio (OR) = 0.36), hypertension (OR = 0.57), diabetes (OR = 0.59), or measured cognitive deficit (OR = 0.40). These women more often had graduated from high school (OR = 1.72) and had participated in other WHI trials (OR = 1.76). LIMITATIONS: We have examined experience with creating follow-up cohorts from participants in a single study. Thus, our findings may not apply to other cohorts and protocols. CONCLUSIONS: Posttrial enrollment in follow-up studies can be successful; however, the characteristics of the resulting cohort may differ substantially from the originally assembled group of trial participants. Collection during the original trial of potential predictors of differential re-enrollment may strengthen interpretation of findings.
    Clinical Trials 03/2013; · 2.20 Impact Factor
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    ABSTRACT: Salt sensitivity, the heterogeneity in the response of blood pressure (BP) to alterations in sodium intake, has been studied extensively, whereas weight sensitivity, the heterogeneity in BP response to weight change, has received scant attention. We examined the relationship of 21 gene polymorphisms previously found to be associated with hypertension, diabetes mellitus, or obesity, with weight sensitivity in the Trial of Nonpharmacologic Interventions in the Elderly, where participants with hypertension were randomized to receive intensive dietary intervention of sodium reduction, weight loss, both, or attention control, whereas pharmacological therapy was kept constant. After correcting for multiplicity, we identified significant associations of 3 polymorphisms with weight sensitivity of systolic BP (rs4646994, rs2820037, and rs1800629) and 3 polymorphisms for diastolic BP (rs4646994, rs2820037, and rs5744292). A recursive partitioning algorithm selected the combination of rs4646994, rs1800629, rs1982073, and rs1800896 as the set associated with the highest weight sensitivity. Polymorphisms related to hypertension, obesity, and diabetes mellitus are associated with weight sensitivity of BP.
    Hypertension 02/2013; · 6.87 Impact Factor
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    ABSTRACT: OBJECTIVE To study the association of depressive symptoms or antidepressant medicine (ADM) use with subsequent cardiovascular disease (CVD) risk factor status in the Look AHEAD (Action for Health in Diabetes) trial of weight loss in type 2 diabetes.RESEARCH DESIGN AND METHODS Participants (n = 5,145; age [mean ± SD] 58.7 ± 6.8 years; BMI 35.8 ± 5.8 kg/m(2)) in two study arms (intensive lifestyle [ILI], diabetes support and education [DSE]) completed the Beck Depression Inventory (BDI), reported ADM use, and were assessed for CVD risk factors at baseline and annually for 4 years. Risk factor-positive status was defined as current smoking, obesity, HbA(1c) >7.0% or insulin use, and blood pressure or cholesterol not at levels recommended by expert consensus panel or medicine to achieve recommended levels. Generalized estimating equations assessed within-study arm relationships of elevated BDI score (≥11) or ADM use with subsequent year CVD risk status, controlled for demographic variables, CVD history, diabetes duration, and prior CVD risk status.RESULTSPrior year elevated BDI was associated (odds ratio [95% CI]) with subsequent CVD risk factor-positive status for the DSE arm (A1C [1.30 (1.09-1.56)]; total cholesterol [0.80 (0.65-1.00)]; i.e., protective from high total cholesterol) and the ILI arm (HDL [1.40 (1.12-1.75)], triglyceride [1.28 (1.00-1.64)]). Prior year ADM use predicted subsequent elevated CVD risk status for the DSE arm (HDL [1.24 (1.03-1.50)], total cholesterol [1.28 (1.05-1.57)], current smoking [1.73 (1.04-2.88)]) and for the ILI arm (A1C [1.25 (1.08-1.46)], HDL [1.32 (1.11-1.58)], triglycerides [1.75 (1.43-2.14)], systolic blood pressure [1.39 (1.11-1.74)]), obesity [1.46 (1.22-2.18)]).CONCLUSIONS Aggressive monitoring of CVD risk in diabetic patients with depressive symptoms or who are treated with ADM may be warranted.
    Diabetes care 01/2013; · 7.74 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. Unique identifier: NCT01072500.
    Journal of the American Heart Association. 01/2013; 2(6):e000257.
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    ABSTRACT: Intraindividual variability among cognitive domains may predict dementia independently of interindividual differences in cognition. A multidomain cognitive battery was administered to 2305 older adult women (mean age 74 years) enrolled in an ancillary study of the Women's Health Initiative. Women were evaluated annually for probable dementia and mild cognitive impairment (MCI) for an average of 5.3 years using a standardized protocol. Proportional hazards regression showed that lower baseline domain-specific cognitive scores significantly predicted MCI (N = 74), probable dementia (N = 45), and MCI or probable dementia combined (N = 101) and that verbal and figural memory predicted each outcome independently of all other cognitive domains. The baseline intraindividual standard deviation across test scores (IAV Cognitive Domains) significantly predicted probable dementia and this effect was attenuated by interindividual differences in verbal episodic memory. Slope increases in IAV Cognitive Domains across measurement occasions (IAV Time) explained additional risk for MCI and MCI or probable dementia, beyond that accounted for by interindividual differences in multiple cognitive measures, but risk for probable dementia was attenuated by mean decreases in verbal episodic memory slope. These findings demonstrate that within-person variability across cognitive domains both at baseline and longitudinally independently accounts for risk of cognitive impairment and dementia in support of the predictive utility of within-person variability.
    Current Gerontology and Geriatrics Research 01/2013; 2013:495793.
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    ABSTRACT: OBJECTIVES: To examine the effects of vitamin D and calcium on cognitive outcomes in elderly women. DESIGN: Post hoc analysis of a randomized double-blind placebo-controlled trial. SETTING: Forty Women's Health Initiative (WHI) clinical centers across the United States. PARTICIPANTS: Four thousand one hundred forty-three women aged 65 and older without probable dementia at baseline who participated in the WHI Calcium and Vitamin D Trial and the WHI Memory Study. INTERVENTION: Two thousand thirty-four women were randomized to receive 1,000 mg of calcium carbonate combined with 400 IU of vitamin D(3) (treatment) and 2,109 to placebo. MEASUREMENTS: Primary: classifications of probable dementia or mild cognitive impairment (MCI) based on a four-phase protocol that included central adjudication. Secondary: global cognitive function and individual cognitive subtests. RESULTS: Mean age of participants was 71. During a mean follow-up of 7.8 years, 39 participants in the treatment group and 37 in the placebo group developed incident dementia (hazard ratio (HR) = 1.11, 95% confidence interval (CI) = 0.71-1.74, P = .64). Likewise, 98 treatment participants and 108 placebo participants developed incident MCI (HR = 0.95, 95% CI = 0.72-1.25, P = .72). There were no significant differences in incident dementia or MCI or in global or domain-specific cognitive function between groups. CONCLUSION: There was no association between treatment assignment and incident cognitive impairment. Further studies are needed to investigate the effects of vitamin D and calcium separately, on men, in other age and ethnic groups, and with other doses.
    Journal of the American Geriatrics Society 11/2012; · 3.98 Impact Factor
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    ABSTRACT: OBJECTIVES: To evaluate the validity and reliability of a cognitive test battery and questionnaires administered by telephone. DESIGN: Observational study; 110 participants randomly assigned to receive two administrations of the same cognitive test battery 6 months apart in one of four combinations (Time 1 administration/Time 2 administration): telephone/telephone, telephone/face to face, face to face/telephone, face to face/face to face. SETTING: Academic medical center. PARTICIPANTS: One hundred ten women aged 65 to 90 without dementia. MEASUREMENTS: The battery included tests of attention; verbal learning and memory; verbal fluency; executive function; working memory; global cognitive functioning; and self-reported measures of perceived memory problems, depressive symptoms, sleep disturbance, and health-related quality of life. Test-retest reliability, concurrent validity, relative bias associated with telephone administration, and change scores were evaluated. RESULTS: There were no statistically significant differences in scores on any of the cognitive tests or questionnaires between participants randomly assigned to telephone or face-to-face administration at the Time 1 assessment, indicating equivalence across administration modes. There was no significant bias for tests or questionnaires administered by telephone (P's > .01), nor was there a difference in mean change scores between administration modes except for Category Fluency (P = .01) and California Verbal Learning Test long-delay free recall (P = .004). Mean test-retest coefficients for the battery were not significantly different between groups, although individual test-retest correlation coefficients were generally higher within modes than between modes. CONCLUSION: Telephone administration of cognitive tests and questionnaires to older women is reliable and valid. Use of telephone batteries can substantially reduce the cost and burden of cognitive assessments and increase enrollment, retention, and data completeness, thereby improving study validity.
    Journal of the American Geriatrics Society 09/2012; 60(9):1616-1623. · 3.98 Impact Factor
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    ABSTRACT: OBJECTIVE To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function.RESEARCH DESIGN AND METHODS Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 72-89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined.RESULTSThe 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01), but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits.CONCLUSIONS Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.
    Diabetes care 08/2012; · 7.74 Impact Factor

Publication Stats

7k Citations
1,054.83 Total Impact Points


  • 1994–2014
    • Wake Forest School of Medicine
      • • Department of Biostatistical Sciences
      • • Division of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 2013
    • Brown University
      Providence, Rhode Island, United States
  • 2012
    • Medical College of Wisconsin
      • Department of Psychiatry and Behavioral Medicine
      Milwaukee, WI, United States
  • 1995–2012
    • Wake Forest University
      • • Department of Health and Exercise Science
      • • Department of Public Health Sciences
      Winston-Salem, North Carolina, United States
    • Fred Hutchinson Cancer Research Center
      Seattle, Washington, United States
  • 2011
    • RAND Corporation
      Santa Monica, California, United States
    • Tufts University
      Georgia, United States
    • Northwestern University
      • Department of Medicine
      Evanston, IL, 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
    • University of Washington Seattle
      • Department of Radiology
      Seattle, WA, United States
    • The University of Tennessee Health Science Center
      • Department of Preventive Medicine
      Memphis, TN, United States
  • 2003
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 2002
    • Robert Wood Johnson University Hospital
      New Brunswick, New Jersey, United States
  • 1999
    • University of Maryland, Baltimore
      • Department of Medicine
      Baltimore, Maryland, United States
  • 1993
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1987–1991
    • UCL Eastman Dental Institute
      Londinium, England, United Kingdom
  • 1987–1990
    • University of Rochester
      Rochester, New York, United States
  • 1989
    • University Center Rochester
      • Department of Biostatistics
      Rochester, Minnesota, United States