Mark A Espeland

Wake Forest University, Winston-Salem, North Carolina, United States

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Publications (226)1265.08 Total impact

  • [Show abstract] [Hide abstract] ABSTRACT: Importance: Weight gain occurs commonly in young adults and has adverse effects on health. Objective: To compare 2 self-regulation interventions vs control in reducing weight gain in young adults over a mean follow-up of 3 years. Design, setting, and participants: Randomized clinical trial in 2 academic settings of 599 participants aged 18 to 35 years with body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 21.0 to 30.0, recruited via mailings and emails from August 2010 to February 2012. Data were analyzed from January 2015 to January 2016. Interventions: Participants were randomized to control, self-regulation plus small changes, or self-regulation plus large changes. Both interventions focused on frequent self-weighing to cue behavior changes. "Small changes" taught participants to reduce intake and increase activity, both by approximately 100 calories per day. "Large changes" focused on losing 2.3 to 4.5 kg initially to buffer against expected weight gain. Main outcomes and measures: Changes in weight from baseline over mean follow-up of 3 years. Secondary outcomes included proportion gaining at least 0.45 kg from baseline, proportion developing obesity (BMI, ≥30.0), and weight change baseline to 2 years. Results: Among the 599 participants (22% men; 27% minority; mean [SD] age, 27.7 [4.4] years; mean [SD] BMI, 25.4 [2.6]), mean (SE) weight changes over a mean follow-up of 3 years were 0.26 (0.22), -0.56 (0.22), and -2.37 (0.22) kg in the control, small-changes, and large-changes groups, respectively (P < .001). Differences among all 3 groups were significant (large changes vs control, P < .001; small changes vs control, P = .02; large changes vs small changes, P < .001). On secondary outcomes, both interventions significantly reduced incidence of obesity relative to control (mean [SE], 8.6% [2.0%], 7.9% [2.0%], and 16.9% [2.7%] in the large-changes, small-changes, and control groups, respectively; P = .02 for large changes vs control and P = .002 for small changes vs control); a smaller percentage of participants in the large-changes group gained 0.45 kg or more (mean [SE], 23.6% [2.8%], 32.5% [3.8%], and 40.8% [4.4%], respectively; P < .001 vs control and P = .02 vs small changes) and weight change from baseline to 2 years was greater in control than in small or large changes (mean [SE], 0.54 [0.33], -0.77 [0.33], and -1.50 [0.34] kg, respectively; P = .02 vs small changes and P < .001 vs large changes). Conclusions and relevance: Self-regulation with large or small changes both reduced weight gain in young adults over 3 years relative to control, but the large-changes intervention was more effective. Trial registration: Identifier: NCT01183689.
    No preview · Article · May 2016 · JAMA Internal Medicine
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    [Show abstract] [Hide abstract] ABSTRACT: OBJECTIVE: Type 2 diabetes increases the accumulation of brain white matter hyperintensities and loss of brain tissue. Behavioral interventions to promote weight loss through dietary changes and increased physical activity may delay these adverse consequences. We assessed whether participation in a successful 10-year lifestyle intervention was associated with better profiles of brain structure. RESEARCH DESIGN AND METHODS: At enrollment in the Action for Health in Diabetes clinical trial, participants had type 2 diabetes, were overweight or obese, and were aged 45-76 years. They were randomly assigned to receive 10 years of lifestyle intervention, which included group and individual counseling, or to a control group receiving diabetes support and education through group sessions on diet, physical activity, and social support. Following this intervention, 319 participants from three sites underwent standardized structural brain magnetic resonance imaging and tests of cognitive function 10-12 years after randomization. RESULTS: Total brain and hippocampus volumes were similar between intervention groups. The mean (SE) white matter hyperintensity volume was 28% lower among lifestyle intervention participants compared with those receiving diabetes support and education: 1.59 (1.11) vs. 2.21 (1.11) cc (P = 0.02). The mean ventricle volume was 9% lower: 28.93 (1.03) vs. 31.72 (1.03) cc (P = 0.04). Assignment to lifestyle intervention was not associated with consistent differences in cognitive function compared with diabetes support and education. CONCLUSIONS: Long-term weight loss intervention may reduce the adverse impact of diabetes on brain structure. Determining whether this eventually delays cognitive decline and impairment requires further research.
    Preview · Article · May 2016 · Diabetes Care
  • [Show abstract] [Hide abstract] ABSTRACT: The purpose of this study is to determine if the effects of cumulative head impacts during a season of high school football produce changes in diffusional kurtosis imaging (DKI) metrics in the absence of clinically diagnosed concussion. Subjects were recruited from a high school football team and were outfitted with the Head Impact Telemetry System (HITs) during all practices and games. Biomechanical head impact exposure metrics were calculated including: total impacts, summed acceleration, and Risk Weighted cumulative Exposure (RWE). Twenty-four players completed pre- and post-season MRI, including DKI; players who experienced clinical concussion were excluded. Fourteen subjects completed pre- and post-season Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT). DKI-derived metrics included mean kurtosis (MK), axial kurtosis (K axial), and radial kurtosis (K radial), and white matter modeling (WMM) parameters included axonal water fraction (AWF), tortuosity of the extra-axonal space, extra-axonal diffusivity (D<sub>e</sub> axial and radial), and intra-axonal diffusivity. These metrics were used to determine the total number of abnormal voxels, defined as 2 standard deviations above or below the group mean. Linear regression analysis revealed a statistically significant relationship between RWE<sub>CP</sub> and MK. Secondary analysis of other DKI-derived and WMM metrics demonstrated statistically significant linear relationships with RWE<sub>CP</sub> after covariate adjustment. These results were compared with the results of DTI-derived metrics from the same imaging sessions in this exact same cohort. Several of the DKI-derived scalars (D<sub>a</sub>, MK, K axial, and K radial) explained more variance when compared to RWE<sub>CP</sub>, suggesting that DKI may be more sensitive to subconcussive head impacts. No significant relationships between DKI-derived metrics and ImPACT measures were found. It is important to note, the pathological implications of these metrics are not well understood. In summary, we demonstrate a single season of high school football can produce DKI measurable changes in the absence of clinically diagnosed concussion.
    No preview · Article · Apr 2016 · Journal of Neurotrauma
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    [Show abstract] [Hide abstract] ABSTRACT: Backgrounds: The Women's Health Initiative Memory Study Magnetic Resonance Imaging (WHIMS-MRI) provides an opportunity to evaluate how menopausal hormone therapy (HT) affects the structure of older women's brains. Our earlier work based on region of interest (ROI) analysis demonstrated potential structural changes underlying adverse effects of HT on cognition. However, the ROI-based analysis is limited in statistical power and precision, and cannot provide fine-grained mapping of whole-brain changes. Methods: We aimed to identify local structural differences between HT and placebo groups from WHIMS-MRI in a whole-brain refined level, by using a novel method, named Optimally-Discriminative Voxel-Based Analysis (ODVBA). ODVBA is a recently proposed imaging pattern analysis approach for group comparisons utilizing a spatially adaptive analysis scheme to accurately locate areas of group differences, thereby providing superior sensitivity and specificity to detect the structural brain changes over conventional methods. Results: Women assigned to HT treatments had significant Gray Matter (GM) losses compared to the placebo groups in the anterior cingulate and the adjacent medial frontal gyrus, and the orbitofrontal cortex, which persisted after multiple comparison corrections. There were no regions where HT was significantly associated with larger volumes compared to placebo, although a trend of marginal significance was found in the posterior cingulate cortical area. The CEE-Alone and CEE+MPA groups, although compared with different placebo controls, demonstrated similar effects according to the spatial patterns of structural changes. Conclusions: HT had adverse effects on GM volumes and risk for cognitive impairment and dementia in older women. These findings advanced our understanding of the neurobiological underpinnings of HT effects.
    Full-text · Article · Mar 2016 · PLoS ONE
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Midlife obesity has been linked to age-related brain atrophy and risk of dementia, but the relationships are less clear for older individuals. These associations may be explained by changes in appetite or metabolism in the dementia prodrome; thus, prospective studies with adequate follow-up are needed. We examined the associations that obesity (body mass index, BMI) and change in BMI over an average of 6.6 (1.0–9.1) years have with global and regional brain and white matter lesion volumes in a sample of 1,366 women aged 65–80. Methods: Least square means for regional brain volumes and white matter lesion loads for women grouped by BMI and changes in BMI were generated from multivariable linear models with and without adjustment for demographic and health covariates. Results: Both global obesity and increase in BMI were associated with lower cerebrospinal fluid and higher specific brain volumes (ps < .05), after controlling for diabetes and other cerebrovascular disease risk factors. Obesity, but not change in BMI, predicted lower lesion loads for the total, parietal, and occipital white matter (ps < .05). Conclusions: Obesity in this cohort is associated with less brain atrophy and lower ischemic lesion loads. The findings are consistent with our previous report of worse cognitive performance in association with weight loss (probably not due to frailty) in this cohort and in line with the idea of the “obesity paradox” as differences in dementia risk vary across time, whereby midlife obesity seems to be a predictor of dementia, whereas weight loss seems to be a better predictor at older ages.
    No preview · Article · Mar 2016 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: To assess the effect of an intensive lifestyle intervention (ILI) compared with standard diabetes support and education (DSE) on preference-based health-related quality of life (HRQOL) in persons with overweight or obesity and type 2 diabetes. Methods: Look AHEAD was a multisite, randomized trial of 5,145 participants assigned to ILI or DSE. Four instruments were administered during the trial: Feeling Thermometer (FT), Health Utilities Index Mark 2 (HUI2), Health Utilities Index Mark 3 (HUI3), and Short Form 6D (SF-6D). Linear mixed effect models were used to estimate the mean difference in preference scores by treatment group for 9 years. Results: The ILI had higher mean FT (0.019, 95% CI, 0.015-0.024, P < 0.001) and SF-6D (0.011, 95% CI, 0.006-0.014, P < 0.001) scores than the DSE. No significant group differences were observed for the HUI2 (0.004, 95% CI, -0.003 to 0.010, P = 0.23) and HUI3 (0.004, -0.004 to 0.012, P = 0.36). In year 1, the ILI had higher mean preference scores for all instruments. Thereafter, the increases remained significant only for FT and SF-6D, and the effects also become smaller. Conclusions: ILI aimed at reducing body weight among persons with overweight or obesity and type 2 diabetes improves preference-based HRQOL in the short term, but its long-term effect is unclear.
    No preview · Article · Mar 2016 · Obesity
  • [Show abstract] [Hide abstract] ABSTRACT: Background. Independent predictors of preserved cognitive functioning and factors associated with maintaining high preserved cognitive function in women ≥80 years remain elusive. Methods. Two thousand two hundred twenty-eight women with a mean age of 85 years who participated in the Women’s Health Initiative Memory Study were classified as cognitively normal (n = 1,905, 85.5%), mild cognitive impairment (n = 88, 3.9%), dementia (n = 121, 5.4%) or other cognitive impairment (n = 114, n = 5.1%) by central adjudication. Global cognitive functioning was assessed using telephone interview for cognitive status-modified in those women who did not meet cognitive impairment criteria. Differences between women grouped by cognitive status with respect to each potential risk factor were assessed using chi-squared tests and t-tests. Backward stepwise logistic regression was used to select factors that were independently associated with cognitive status. Results. Factors associated with preserved cognitive functioning were younger age, higher education, and family incomes, being non-Hispanic white, better emotional wellbeing, fewer depressive symptoms, more insomnia complaints, being free of diabetes, and not carrying the apolipoprotein E-epsilon 4 allele. Cognitively normal women who demonstrated sustained high preserved cognition were younger, more educated, and endorsed better self-reported general health, emotional wellbeing, and higher physical functioning. Conclusions. Addressing sociodemographic disparities such as income inequality, and targeting interventions to improve depressive symptoms and vascular risk factors, including diabetes, may play an important role in preserving cognition among women who survive to 80 years of age. Person-centered approaches that combine interventions to improve physical, cognitive, and psychosocial functioning may promote maintenance of high preserved cognitive health in the oldest-old.
    No preview · Article · Mar 2016 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Losing the ability to walk safely and independently is a major concern for many older adults. The Lifestyle Interventions and Independence for Elders study recently demonstrated that a physical activity (PA) intervention can delay the onset of major mobility disability. Our objective is to examine the resources required to deliver the PA intervention and calculate the incremental cost-effectiveness compared with a health education intervention. Methods: The Lifestyle Interventions and Independence for Elders study enrolled 1,635 older adults at risk for mobility disability. They were recruited at eight field centers and randomly assigned to either PA or health education. The PA program consisted of 50-minute center-based exercise 2× weekly, augmented with home-based activity to achieve a goal of 150min/wk of PA. Health education consisted of weekly workshops for 26 weeks, and monthly sessions thereafter. Analyses were conducted from a health system perspective, with a 2.6-year time horizon. Results: The average cost per participant over 2.6 years was US$3,302 and US$1,001 for the PA and health education interventions, respectively. PA participants accrued 0.047 per person more Quality-Adjusted Life-Years (QALYs) than health education participants. PA interventions costs were slightly higher than other recent PA interventions. The incremental cost-effectiveness ratios were US$42,376/major mobility disability prevented and US$49,167/QALY. Sensitivity analyses indicated that results were relatively robust to varied assumptions. Conclusions: The PA intervention costs and QALYs gained are comparable to those found in other studies. The ICERS are less than many commonly recommended medical treatments. Implementing the intervention in non-research settings may reduce costs further.
    No preview · Article · Feb 2016 · The Journals of Gerontology Series A Biological Sciences and Medical Sciences
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    [Show abstract] [Hide abstract] ABSTRACT: Context The relations between dietary and/or circulating levels of fatty acids and the development of type 2 diabetes is unclear. Protective associations with the marine omega-3 fatty acids and linoleic acid, and with a marker of fatty acid desaturase activity delta-5 desaturase (D5D ratio) have been reported, as have adverse relations with saturated fatty acids and D6D ratio. Objective To determine the associations between red blood cell (RBC) fatty acid distributions and incident type 2 diabetes. Design Prospective observational cohort study nested in the Women's Health Initiative Memory Study. Setting General population. Subjects Postmenopausal women. Main Outcome Measures Self-reported incident type 2 diabetes. Results There were 703 new cases of type 2 diabetes over 11 years of follow up among 6379 postmenopausal women. In the fully adjusted models, baseline RBC D5D ratio was inversely associated with incident type 2 diabetes [Hazard Ratio (HR) 0.88, 95% confidence interval (CI) 0.81-0.95) per 1 SD increase. Similarly, baseline RBC D6D ratio and palmitic acid were directly associated with incident type 2 diabetes (HR 1.14, 95% CI 1.04-1.25; and HR 1.24, 95% CI 1.14-1.35, respectively). None of these relations were materially altered by excluding incident cases in the first two years of follow-up. There were no significant relations with eicosapentaenoic, docosahexaenoic or linoleic acids. Conclusions Whether altered fatty acid desaturase activities or palmitic acid levels are causally related to the development of type 2 diabetes cannot be determined from this study, but our findings suggest that proportions of certain fatty acids in RBC membranes are associated with risk for type 2 diabetes. © 2016 Harris et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
    Preview · Article · Feb 2016 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Purpose of the study: A comparison of longitudinal global cognitive functioning in women Veteran and non-Veteran participants in the Women's Health Initiative (WHI). Design and methods: We studied 7,330 women aged 65-79 at baseline who participated in the WHI Hormone Therapy Trial and its ancillary Memory Study (WHIMS). Global cognitive functioning (Modified Mini-Mental State Examination [3MSE]) in Veterans (n = 279) and non-Veterans (n = 7,051) was compared at baseline and annually for 8 years using generalized linear modeling methods. Results: Compared with non-Veterans, Veteran women were older, more likely to be Caucasian, unmarried, and had higher rates of educational and occupational attainment. Results of unadjusted baseline analyses suggest 3MSE scores were similar between groups. Longitudinal analyses, adjusted for age, education, ethnicity, and WHI trial assignment revealed differences in the rate of cognitive decline between groups over time, such that scores decreased more in Veterans relative to non-Veterans. This relative difference was more pronounced among Veterans who were older, had higher educational/occupational attainment and greater baseline prevalence of cardiovascular risk factors (e.g., smoking) and cardiovascular disease (e.g., angina, stroke). Implications: Veteran status was associated with higher prevalence of protective factors that may have helped initially preserve cognitive functioning. However, findings ultimately revealed more pronounced cognitive decline among Veteran relative to non-Veteran participants, likely suggesting the presence of risks that may impact neuropathology and the effects of which were initially masked by Veterans' greater cognitive reserve.
    Full-text · Article · Feb 2016 · The Gerontologist
  • [Show abstract] [Hide abstract] ABSTRACT: Genetic studies have identified a glutamate-ammonia ligase gene (GLUL) polymorphism associated with cardiovascular disease morbidity and mortality among people with type 2 diabetes (T2D). We sought to determine whether GLUL rs10911021 is associated prospectively with adjudicated cardiovascular composite end points among overweight/obese individuals with T2D and whether a lifestyle intervention resulting in weight loss could diminish this association. Look AHEAD is a randomized, controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Look AHEAD participants included in this report were 3,845 overweight/obese individuals with T2D who provided consent for genetic analyses. Over a median of 9.6 years of follow-up, the risk (C) allele for GLUL rs10911021 was significantly associated with the primary composite end point of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for angina among individuals with no history of cardiovascular disease (CVD) at baseline using additive genetic models (hazard ratio 1.17(95% CI 1.01-1.36]; P = 0.032). Results appeared more consistent in recessive models and among individuals with no known history of CVD at baseline; ILI did not alter these associations. These results extend the association of GLUL rs10911021 to incident CVD morbidity and mortality in the setting of T2D.
    No preview · Article · Jan 2016 · Diabetes
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    [Show abstract] [Hide abstract] ABSTRACT: In Brief This article reports on an investigation of whether an intensive lifestyle intervention (ILI) would reduce gastrointestinal symptoms over 4 years of follow-up for participants in the Action for Health in Diabetes (Look AHEAD) trial compared to a diabetes support and education (DSE) group. Look AHEAD is a randomized, multicenter trial comparing overweight and obese adults with type 2 diabetes treated with ILI versus DSE. ILI, and weight loss in general, had beneficial effects on gastrointestinal (GI) symptoms, with some variability in the strength of the effect depending on the specific symptom and time course. Potential modifiers were analyzed, yet ILI retained an association with improvement in GI symptoms.
    Preview · Article · Oct 2015 · Clinical Diabetes
  • [Show abstract] [Hide abstract] ABSTRACT: Objective: In older women, higher levels of estrogen may exacerbate the increased risk for cognitive impairment conveyed by diabetes. We examined whether the effect of postmenopausal hormone therapy (HT) on cognitive impairment incidence differs depending on type 2 diabetes. Research design and methods: The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without [i.e., unopposed] 2.5 mg/day medroxyprogesterone acetate) or matching placebo for an average of 4.7-5.9 years. A total of 7,233 women, ages 65-80 years, were classified according to type 2 diabetes status and followed for probable dementia and cognitive impairment (mild cognitive impairment or dementia). Results: Through a maximum of 18 years of follow-up, women with diabetes had increased risk of probable dementia (hazard ratio [HR] 1.54 [95% CI 1.16-2.06]) and cognitive impairment (HR 1.83 [1.50-2.23]). The combination of diabetes and random assignment to HT increased their risk of dementia (HR 2.12 [1.47-3.06]) and cognitive impairment (HR 2.20 [1.70-2.87]) compared with women without these conditions: interactions P = 0.09 and P = 0.08. These interactions appeared to be limited to women assigned to unopposed conjugated equine estrogens. Conclusions: These analyses provide additional support to a prior report that higher levels of estrogen may exacerbate risks that type 2 diabetes poses for cognitive function in older women. The role estrogen plays in suppressing non-glucose based energy sources in the brain may explain this interaction.
    No preview · Article · Oct 2015 · Diabetes care
  • [Show abstract] [Hide abstract] ABSTRACT: Epidemiological evidence suggests that physical activity benefits cognition, but results from randomized trials are limited and mixed. To determine whether a 24-month physical activity program results in better cognitive function, lower risk of mild cognitive impairment (MCI) or dementia, or both, compared with a health education program. A randomized clinical trial, the Lifestyle Interventions and Independence for Elders (LIFE) study, enrolled 1635 community-living participants at 8 US centers from February 2010 until December 2011. Participants were sedentary adults aged 70 to 89 years who were at risk for mobility disability but able to walk 400 m. A structured, moderate-intensity physical activity program (n = 818) that included walking, resistance training, and flexibility exercises or a health education program (n = 817) of educational workshops and upper-extremity stretching. Prespecified secondary outcomes of the LIFE study included cognitive function measured by the Digit Symbol Coding (DSC) task subtest of the Wechsler Adult Intelligence Scale (score range: 0-133; higher scores indicate better function) and the revised Hopkins Verbal Learning Test (HVLT-R; 12-item word list recall task) assessed in 1476 participants (90.3%). Tertiary outcomes included global and executive cognitive function and incident MCI or dementia at 24 months. At 24 months, DSC task and HVLT-R scores (adjusted for clinic site, sex, and baseline values) were not different between groups. The mean DSC task scores were 46.26 points for the physical activity group vs 46.28 for the health education group (mean difference, -0.01 points [95% CI, -0.80 to 0.77 points], P = .97). The mean HVLT-R delayed recall scores were 7.22 for the physical activity group vs 7.25 for the health education group (mean difference, -0.03 words [95% CI, -0.29 to 0.24 words], P = .84). No differences for any other cognitive or composite measures were observed. Participants in the physical activity group who were 80 years or older (n = 307) and those with poorer baseline physical performance (n = 328) had better changes in executive function composite scores compared with the health education group (P = .01 for interaction for both comparisons). Incident MCI or dementia occurred in 98 participants (13.2%) in the physical activity group and 91 participants (12.1%) in the health education group (odds ratio, 1.08 [95% CI, 0.80 to 1.46]). Among sedentary older adults, a 24-month moderate-intensity physical activity program compared with a health education program did not result in improvements in global or domain-specific cognitive function. Identifier: NCT01072500.
    No preview · Article · Aug 2015 · JAMA The Journal of the American Medical Association
  • [Show abstract] [Hide abstract] ABSTRACT: To examine whether the effect of postmenopausal hormone therapy (HT) on brain volumes in women aged 65-79 years differs depending on type 2 diabetes status during postintervention follow-up of a randomized controlled clinical trial. The Women's Health Initiative randomized clinical trials assigned women to HT (0.625 mg/day conjugated equine estrogens with or without 2.5 mg/day medroxyprogesterone acetate) or placebo for an average of 5.6 years. A total of 1,402 trial participants underwent brain MRI 2.4 years after the trials; these were repeated in 699 women 4.7 years later. General linear models were used to assess the interaction between diabetes status and HT assignment on brain volumes. Women with diabetes at baseline or during follow-up who had been assigned to HT compared to placebo had mean decrement in total brain volume of -18.6 mL (95% confidence interval [CI] -29.6, -7.6). For women without diabetes, this mean decrement was -0.4 (95% CI -3.8, 3.0) (interaction p = 0.002). This interaction was evident for total gray matter (p < 0.001) and hippocampal (p = 0.006) volumes. It was not evident for changes in brain volumes over follow-up or for ischemic lesion volumes and was not influenced by diabetes duration or oral medications. For women aged 65 years or older who are at increased risk for brain atrophy due to type 2 diabetes, prescription of postmenopausal HT is associated with lower gray matter (total and hippocampal) volumes. Interactions with diabetes and insulin resistance may explain divergent findings on how estrogen influences brain volume among older women. © 2015 American Academy of Neurology.
    No preview · Article · Jul 2015 · Neurology
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  • [Show abstract] [Hide abstract] ABSTRACT: To examine the putative adverse effects of ambient fine particulate matter (PM2.5 ) on brain volumes in older women. We conducted a prospective study of 1403 community-dwelling older women without dementia enrolled in the Women's Health Initiative Memory Study (WHIMS), 1996-8. Structural brain MRI scans were performed at age of 71-89 years in 2005-6 to obtain volumetric measures of gray matter (GM) and normal-appearing white matter (WM). Given residential histories and air monitoring data, we used a spatiotemporal model to estimate cumulative PM2.5 exposure in 1999-2006. Multiple linear regression was employed to evaluate the associations between PM2.5 and brain volumes, adjusting for intracranial volumes and potential confounders. Older women with greater PM2.5 exposures had significantly smaller WM, but not GM volumes, independent of geographic region, demographics, socioeconomic status, lifestyles, and clinical characteristics including cardiovascular risk factors. For each inter-quartile increment (3.49 µg/m(3) ) of cumulative PM2.5 exposure, the average WM volume (95% confidence interval) was 6.23 (3.72-8.74) cm(3) in the total brain and 4.47 (2.27-6.67) cm(3) lower in the association areas, equivalent to 1-2 years of brain aging. The adverse PM2.5 effects on smaller WM volumes were present in frontal and temporal lobes and corpus callosum (all p-values <0.01). Hippocampal volumes did not differ by PM2.5 exposure. PM2.5 exposure may contribute to WM loss in older women. Future studies are needed to determine whether exposures result in myelination disturbance, disruption of axonal integrity, damages to oligodendrocytes, or other WM neuropathologies. This article is protected by copyright. All rights reserved. © 2015 American Neurological Association.
    No preview · Article · Jun 2015 · Annals of Neurology
  • [Show abstract] [Hide abstract] ABSTRACT: An estimated 65% of individuals demonstrate multidomain cognitive impairment poststroke, although little is known about the varying role of cognitive risk and protective factors in preischemic, peri-ischemic, and postischemic stroke phases. Longitudinal changes in global cognitive function after ischemic stroke are not well characterized, especially in older adults over age 80. We examined global cognitive function trajectories in these three phases across a mean follow-up of 8.12 (2.30) years in 159 female stroke survivors aged 65-79 at baseline using linear mixed models with change points. In separate models controlling for demographic variables, we tested the interaction of baseline risk and protective factors with stroke phase on global cognitive function. None of the prestroke global cognitive function means or trajectories differed significantly. At the time of ischemic stroke, higher body mass index (BMI), the presence of hypertension (HTN), low optimism, and higher physical function were all associated with significantly greater mean decreases in global cognition (all p's <.0.0001), but were not significantly different from the contrasting level (all p's >0.05). Higher BMI, the presence of HTN, low optimism, and higher physical function were in turn protective of global cognitive decline postischemic stroke (all contrasting p values <.01). Baseline factors may play either a risk or a protective role in global cognitive function depending on the phase of ischemic stroke.
    No preview · Article · Jun 2015 · Aging Neuropsychology and Cognition
  • [Show abstract] [Hide abstract] ABSTRACT: Consistent evidence linking habitual sleep duration with risks of mild cognitive impairment (MCI) and dementia is lacking. We conducted a prospective study on 7444 community-dwelling women (aged 65-80 y) with self-reported sleep duration, within the Women's Health Initiative Memory Study in 1995-2008. Incident MCI/dementia cases were ascertained by validated protocols. Cox models were used to adjust for multiple sociodemographic and lifestyle factors, depression, cardiovascular disease (CVD), and other clinical characteristics. We found a statistically significant (P = .03) V-shaped association with a higher MCI/dementia risk in women with either short (≤6 hours/night) or long (≥8 hours/night) sleep duration (vs. 7 hours/night). The multicovariate-adjusted hazard for MCI/dementia was increased by 36% in short sleepers irrespective of CVD, and by 35% in long sleepers without CVD. A similar V-shaped association was found with cognitive decline. In older women, habitual sleep duration predicts the future risk for cognitive impairments including dementia, independent of vascular risk factors. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Jun 2015 · Alzheimer's & dementia: the journal of the Alzheimer's Association

Publication Stats

10k Citations
1,265.08 Total Impact Points


  • 2015
    • Wake Forest University
      • Department of Biostatistical Sciences
      Winston-Salem, North Carolina, United States
  • 2007
    • Wake Forest School of Medicine
      • Division of Public Health Sciences
      Winston-Salem, North Carolina, United States
  • 2003
    • Pennington Biomedical Research Center
      Baton Rouge, Louisiana, United States
  • 1997
    • Stanford University
      Palo Alto, California, United States
  • 1985
    • University of Rochester
      • School of Medicine and Dentistry
      Rochester, New York, United States