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1.  Night shift work at specific age ranges and chronic disease risk factors 
We examined the association of night shift work history and age when night shift work was performed with cancer and cardiovascular disease risk factors among 54 724 women in the Nurses' Health Study (NHS) II.
We calculated age-adjusted and socioeconomic status-adjusted means and percentages for cancer and cardiovascular risk factors in 2009 across categories of night shift work history. We used multivariable-adjusted logistic regression to estimate odds ratios (ORs) and 95% CIs for key risk factors among 54 724 participants (72% ever shift workers). We further examined these associations by age (20–25, 26–35, 36– 45 and 46+ years) at which shift work was performed.
Ever night shift workers had increased odds of obesity (body mass index ≥30 kg/m2; OR=1.37, 95% CI 1.31 to 1.43); higher caffeine intake (≥131 mg/day; OR=1.16, 95% CI 1.12 to 1.22) and total calorie intake (≥1715 kcal/day; OR=1.09, 95% CI 1.04 to 1.13); current smoking (OR=1.30, 95% CI 1.19 to 1.42); and shorter sleep durations (≤7 h of sleep/day; OR=1.19, 95% CI 1.15 to 1.24) compared to never night shift workers. These estimates varied depending on age at which night work was performed, with a suggestion that night shift work before age 25 was associated with fewer risk factors compared to night shift work at older ages.
Our results indicate that night shift work may contribute to an adverse chronic disease risk profile, and that risk factors may vary depending on the age at which night shift work was performed.
PMCID: PMC4289641  PMID: 25261528
Chronobiology international  2013;30(9):1181-1186.
The aim of this study was to examine the relation between chronotype and breast cancer risk. We analyzed the association between chronotype (definite morning type, probable morning type, probable evening type, definite evening type, or neither morning nor evening type) and breast cancer risk among 72 517 women in the Nurses’ Health Study II (NHS II). Chronotype was self-reported in 2009, and 1834 breast cancer cases were confirmed among participants between 1989–2007; a 2-year lag period was imposed to account for possible circadian disruptions related to breast cancer diagnosis. Age- and multivariable-adjusted logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Participants who self-reported as neither morning nor evening chronotype had a 27% increased risk of breast cancer (multivariable-adjusted OR= 1.27; 95% CI, 1.04–1.56), compared to definite morning types. None of the other chronotypes were significantly associated with breast cancer risk (multivariable-adjusted OR= .99, 95% CI, .87–1.12 for probable morning vs. definite morning types, OR=.96, 95% CI, .84–1.09 for probable evening vs. definite morning types, and OR=1.15, 95% CI, .98–1.34 for definite evening vs. definite morning types). Overall, chronotype was not associated with breast cancer risk in our study. A modestly increased risk among neither morning nor evening chronotypes may indicate circadian disruption as a potentially underlying mechanism; however, more studies are needed to confirm our results.
PMCID: PMC4007068  PMID: 23961712
chronotype; night shift work; breast cancer; morningness-eveningness; bimodal
3.  Shift Work and Cognition in the Nurses' Health Study 
American Journal of Epidemiology  2013;178(8):1296-1300.
Rotating night-shift work, which can disrupt circadian rhythm, may adversely affect long-term health. Experimental studies indicate that circadian rhythm disruption might specifically accelerate brain aging; thus, we prospectively examined shift-work history at midlife as associated with cognitive function among older women in the Nurses' Health Study. Women reported their history of rotating night-shift work in 1988 and participated in telephone-based cognitive interviews between 1995 and 2001; interviews included 6 cognitive tests that were subsequently repeated 3 times, at 2-year intervals. We focused on shift work through midlife (here, ages 58–68 years) because cognitive decline is thought to begin during this period. Using multivariable-adjusted linear regression, we evaluated mean differences in both “average cognitive status” at older age (averaging cognitive scores from all 4 interviews) and rates of cognitive decline over time across categories of shift-work duration at midlife (none, 1–9, 10–19, or ≥20 years). There was little association between shift work and average cognition in later life or between shift work and cognitive decline. Overall, this study does not clearly support the hypothesis that shift-work history in midlife has long-term effects on cognition in older adults.
PMCID: PMC3792735  PMID: 24076971
circadian rhythm; cognition; nurses; shift work
4.  Factors associated with persistent urinary incontinence 
Many women with urinary incontinence (UI) have symptoms that continue over many years; however, virtually nothing is known about factors that are associated with persistent UI.
Study design
We studied 36,843 participants of the Nurses’ Health Study, aged 54–79 years at baseline for the UI study, who provided UI information on biennial questionnaires from 2000 to 2008; follow up in the Nurses’ Health Study is 90%. In total, 18,347 women had “persistent UI,” defined as urine leakage ≥1/month reported on all five biennial questionnaires during this eight-year period; 18,496 women had no UI during this period. Using multivariable-adjusted logistic regression, we estimated odds ratios (OR) of persistent UI versus no UI across various demographic, lifestyle, and health-related factors, which were derived from reports in 2000.
Increasing age group, white race, greater parity, greater BMI, and lower physical activity levels were each associated with greater odds of persistent UI, as were several health-related factors (i.e., stroke, type 2 diabetes, and hysterectomy). Associations with persistent UI were particularly strong for increasing age group (p-trend<0.0001; OR=2.75, 95% CI=2.54–2.98 comparing women aged ≥75 vs. <60 years) and greater BMI (p-trend<0.0001; OR=3.14, 95% CI=2.95–3.33 comparing women with BMI ≥30 vs. <25 kg/m2); moreover, black women had much lower odds of persistent UI compared to white women (OR=0.27, 95% CI=0.21–0.34).
Factors associated with persistent UI were generally consistent with those identified in previous studies of UI over shorter time periods; however, older age, white race, and obesity were particularly strongly related to persistent UI.
PMCID: PMC3729752  PMID: 23659990
epidemiology; risk factors; urinary incontinence; women
5.  Severity of Urinary Incontinence and Effect on Quality of Life in Women, by Incontinence Type 
Obstetrics and gynecology  2013;121(5):1083-1090.
To estimate how symptom severity, extent of bother, and quality of life differ across urinary incontinence (UI) subtypes.
We evaluated prevalent UI cases from the Nurses' Health Studies, including women aged 41–83 years. Women with UI (leaking more than once a month) were subclassified according to reported symptoms as stress (leakage with activity), urgency (leakage with urgency), or mixed UI (stress and urgency co-occurring equally). UI severity was assessed in 102,418 women, based on the Sandvik severity index. In a subset of older women with weekly UI, we asked about bother (n=1,697) and quality of life (Incontinence Impact Questionnaire; n=1,748). UI severity, bother, and quality of life were compared across subtypes using polytomous logistic regression, adjusting for other characteristics.
The distribution of UI subtypes was 51% stress, 27% urgency, and 22% mixed UI. About half had slight UI, 26% had moderate, and 23% had severe UI. Severe UI was more common in women reporting mixed (37%), than urgency (27%) or stress UI symptoms (15%) (P<0.001). More women with severe mixed (21%, P=0.02) and urgency UI symptoms (13%, P=0.1) reported being “greatly” bothered by their UI, compared with stress UI (10%). Women with severe mixed (mean 18.0, P<0.001) and urgency UI symptoms (mean 13.4, P=0.004) had higher mean Incontinence Impact scores compared with stress UI (mean 9.8).
Women reporting mixed UI symptoms describe more severe and bothersome incontinence, with higher effect on quality of life.
PMCID: PMC3959868  PMID: 23635747
Introduction and hypothesis
Acidic fruits are commonly cited in the lay press as potential bladder irritants that may promote urinary incontinence (UI), but no epidemiologic studies have examined this issue. We hypothesized that higher intake of acidic fruits might be related to greater risk of UI incidence and progression in women.
In one set of analyses, we included women without UI at study baseline in the Nurses’ Health Studies (NHS), with 34,144 women aged 54–79 in NHS I and 31,024 women aged 37–54 in NHS II. These cohorts were established among women living in the United States. Incident UI was ascertained over four years of follow up, and acidic fruit consumption was measured by food frequency questionnaire prior to UI onset. In a second set of analyses, we examined UI progression over two years of follow up among 11,764 women in NHS I and 11,299 women in NHS II with existing UI. Multivariable-adjusted relative risks were calculated for the associations of acidic fruit intake and UI incidence and progression.
We found no relation between acidic fruit intake and risk of developing UI, including urgency, mixed, and stress UI. In addition, there was no association between consumption of acidic fruits and UI progression, regardless of UI type.
No associations were detected between acidic fruit intake and UI in this large, prospective study of women. These data have implications for the development of evidence-based dietary guidelines around acidic fruits and UI, particularly because acidic fruits likely have many health benefits.
PMCID: PMC3558558  PMID: 22878474
aging; cohort studies; diet; epidemiology; urinary incontinence
7.  Total antioxidant capacity of the diet and major neurologic outcomes in older adults 
Neurology  2013;80(10):904-910.
To evaluate total antioxidant capacity of the diet, measured by the ferric-reducing antioxidant power (FRAP) assay, in relation to risks of dementia and stroke, as well as key structural brain volumes, in the elderly.
We prospectively studied 5,395 participants in the Rotterdam Study, aged 55 years and older, who were dementia free and provided dietary information at study baseline; 5,285 individuals were also stroke free at baseline, and 462 were dementia and stroke free at the time of an MRI brain scan 5 years after baseline. Dietary data were ascertained using a semiquantitative food-frequency questionnaire, and combined with food-specific FRAP measurements from published tables; this information was aggregated across the diet to obtain “dietary FRAP scores.” Multivariable-adjusted Cox proportional hazard models were used to estimate relative risks of dementia and stroke, and multivariable-adjusted linear regression was used to estimate mean differences in structural brain volumes, across tertiles of dietary FRAP scores.
During a median 13.8 years of follow-up, we identified approximately 600 cases each of dementia and stroke. In multivariable-adjusted models, we observed no associations between dietary FRAP scores and risk of dementia (p trend = 0.3; relative risk = 1.12, 95% confidence interval = 0.91–1.38, comparing the highest vs lowest FRAP tertiles) or risk of stroke (p trend = 0.3; relative risk = 0.91, 95% confidence interval = 0.75–1.11, comparing extreme FRAP tertiles); results were similar across subtypes of these outcomes. Dietary FRAP scores were unrelated to brain tissue volumes as well.
Total antioxidant capacity of the diet, measured by dietary FRAP scores, does not seem to predict risks of major neurologic diseases.
PMCID: PMC3653208  PMID: 23427318
8.  The Association of Antioxidants and Cognition in the Nurses’ Health Study 
American Journal of Epidemiology  2012;177(1):33-41.
The authors examined long-term antioxidant intake in relation to cognitive decline among older women. Beginning in 1980, Nurses’ Health Study (NHS) participants completed dietary assessments every 4 years; in 1995–2001, 16,010 participants aged ≥70 years completed initial cognitive assessments, which were repeated 3 times at 2-year intervals. Long-term antioxidant intake was averaged from 1980 through the time of initial cognitive interviews. Multivariable-adjusted linear regression was used to estimate mean differences in rates of cognitive decline across categories of vitamin E, vitamin C, and carotenoid intake; statistical tests were 2-sided. No associations were evident for vitamin E or total carotenoid intake and cognitive decline (e.g., after multivariable adjustment, P-trend = 0.44 and P-trend = 0.51, respectively, for a global composite score averaging all 6 cognitive tests), although higher lycopene intake and lower vitamin C intake were related to slower cognitive decline. In alternative analyses of overall cognitive status at older ages (averaging all 4 cognitive assessments), results for vitamins E and C were generally null, but higher carotenoid intake was related to better cognition. Overall, long-term vitamin E and C intakes were not consistently related to cognition, although greater consumption of carotenoids may have cognitive benefits in older adults.
PMCID: PMC3590037  PMID: 23221724
antioxidants; cognition; cohort studies; diet
The Journal of urology  2012;188(5):1816-1821.
Little research has investigated the epidemiology of urinary incontinence (UI) in individuals with type 2 diabetes (T2D). We examined prevalence, incidence, and risk factors for UI among women with T2D in the Nurses’ Health Study (NHS) and NHS II.
Materials and Methods
We obtained UI information at study baseline (2000 in NHS and 2001 in NHS II) and two follow ups (2002 and 2004 in NHS, and 2003 and 2005 in NHS II). Among women with T2D, we calculated UI prevalence for 9,994 women with baseline UI information, and UI incidence rates for 4,331 women with no UI at baseline and UI information during follow up. Multivariable-adjusted odds ratios (ORs) and relative risks (RRs) were estimated for associations between possible risk factors and UI.
Prevalence of at least monthly UI was 48% and at least weekly UI was 29% among women with T2D; corresponding incidence rates were 9.1 and 3.4 per 100 person-years, respectively. White race, higher BMI, higher parity, lower physical activity, current post-menopausal hormone use, and diuretic use were risk factors for prevalent and incident UI in this study, and hysterectomy, vascular disease, and longer duration of diabetes were associated with increased odds of prevalent UI only. Increasing age and microvascular complications were associated with greater risk of developing frequent UI.
UI was very common in this study of women with T2D. We identified multiple risk factors for UI in these women, several of which suggest ways for women with T2D to reduce UI.
PMCID: PMC3646531  PMID: 22999689
urinary incontinence; type 2 diabetes; epidemiology; women
10.  Dietary intake of berries and flavonoids in relation to cognitive decline 
Annals of neurology  2012;72(1):135-143.
Berries are high in flavonoids, especially anthocyanidins, and improve cognition in experimental studies. We prospectively evaluated whether greater long-term intakes of berries and flavonoids are associated with slower rates of cognitive decline in older women.
Beginning in 1980, a semi-quantitative food frequency questionnaire was administered every four years to Nurses’ Health Study participants. In 1995–2001, we began measuring cognitive function in 16,010 participants, aged ≥70 years; follow-up assessments were conducted twice, at two-year intervals. To ascertain long-term diet, we averaged dietary variables from 1980 through the initial cognitive interview. Using multivariable-adjusted, mixed linear regression, we estimated mean differences in slopes of cognitive decline by long-term berry and flavonoid intakes.
Greater intakes of blueberries and strawberries were associated with slower rates of cognitive decline (e.g., for a global score averaging all six cognitive tests, for blueberries: p-trend=0.014 and mean difference=0.04 [95% CI=0.01, 0.07] comparing extreme categories of intake; for strawberries: p-trend= 0.022 and mean difference=0.03 [95% CI=0.00, 0.06] comparing extreme categories of intake), after adjusting for multiple potential confounders. These effect estimates were equivalent to those we find for approximately 1.5 to 2.5 years of age in our cohort, indicating that berry intake appears to delay cognitive aging by up to 2.5 years. Additionally, in further supporting evidence, greater intakes of anthocyanidins and total flavonoids were associated with slower rates of cognitive decline (p-trends= 0.015 and 0.053, respectively, for the global score).
Higher intake of flavonoids, particularly from berries, appears to reduce rates of cognitive decline in older adults.
PMCID: PMC3582325  PMID: 22535616
11.  Relative Telomere Length and Cognitive Decline in the Nurses’ Health Study 
Neuroscience Letters  2011;492(1):15-18.
Telomeres are short DNA repeats on the ends of mammalian chromosomes, which can undergo incomplete replication leading to gradual shortening with each cell cycle. Age and oxidative stress are contributors to telomere shortening; thus, telomere length may be a composite measure of biologic aging, and a potential predictor of health status in older adults. We evaluated whether relative telomere length (the proportion of telomere repeat copy number to single gene copy number, using a real-time PCR method) predicts cognitive decline measured ten years later among ~2,000 older participants in the Nurses’ Health Study (NHS). Mixed linear regression was used to evaluate mean differences in cognitive decline according to telomere length. After adjustment for potential confounders, we found that decreasing telomere length was associated with more cognitive decline, although associations were modest (e.g. for a global score, averaging all six tests in our cognitive battery, mean difference=0.03 standard units per SD increase in telomere length; p=0.04). The magnitude of these estimates was similar to the differences we find in this cohort for women one year apart in age (e.g. the differences that we observe between women who are 73 versus 74 years of age); thus, our results suggest that telomere length is not a particularly powerful marker of impending cognitive decline.
PMCID: PMC3306217  PMID: 21295115
Telomeres; cognitive function; aging; epidemiology
12.  Dietary antioxidants and long-term risk of dementia 
Archives of neurology  2010;67(7):819-825.
To study consumption of major dietary antioxidants in relation to long-term risk of dementia.
The Rotterdam Study, a population-based, prospective cohort study in the Netherlands.
A total of 5,395 participants, aged 55+ years, who were free of dementia and provided dietary information at study baseline.
Incidence of dementia and Alzheimer’s disease (AD), based on internationally accepted criteria, in relation to dietary intake of vitamin E, vitamin C, beta carotene, and flavonoids.
During an average follow-up period of 9.6 years, dementia developed in 465 participants, of whom 365 were diagnosed with AD. In multivariate models adjusted for age, education, APOE ε4 genotype, total energy intake, alcohol intake, smoking habits, body-mass index (BMI), and supplement use, higher intake of vitamin E at baseline was associated with a lower long-term risk of dementia (p-trend=0.02). Compared to participants in the lowest tertile of vitamin E intake, those in the highest tertile were 25% less likely to develop dementia (HR, 0.75; 95% CI, 0.59–0.95 with adjustment for potential confounders). Dietary intakes of vitamin C, beta carotene, and flavonoids were not associated with dementia risk (after multivariate adjustment, p-trend=1.0 for both vitamin C and beta carotene and p-trend=0.6 for flavonoids). Results were similar when AD risk was specifically examined.
Higher intake of foods rich in vitamin E may modestly reduce long-term risk of dementia and AD.
PMCID: PMC2923546  PMID: 20625087
13.  Physical Activity Levels and Cognition in Women With Type 2 Diabetes 
American Journal of Epidemiology  2009;170(8):1040-1047.
Persons with type 2 diabetes have a high risk of late-life cognitive impairment, and physical activity might be a potential target for modifying this risk. Therefore, the authors evaluated the association between physical activity level and cognition in women with type 2 diabetes. Beginning in 1995–2000, cognitive function was assessed in 1,550 Nurses’ Health Study participants aged ≥70 years with type 2 diabetes. Follow-up assessments were completed twice thereafter, at 2-year intervals. Multivariate-adjusted linear regression models were used to obtain mean differences in baseline cognitive scores and cognitive decline across tertiles of long-term physical activity. Initial results from age- and education-adjusted models indicated that greater physical activity levels were associated with better baseline cognition (for a global score averaging scores from 6 cognitive tests, P-trend = 0.02). However, results were substantially attenuated after adjustment for multiple potential confounders, largely because of physical disability indicators (global score: P-trend = 0.06); for example, the mean difference for the global score was 0.07 standard units (95% confidence interval: −0.01, 0.15) when comparing extreme tertiles. Results were similar for cognitive decline. These findings indicate little overall association between physical activity and cognition after adjustment for disability factors in older women with type 2 diabetes.
PMCID: PMC2765365  PMID: 19729385
cognition; cohort studies; diabetes mellitus, type 2; exercise; women
14.  The relation between moderate alcohol consumption and cognitive function in older women with type 2 diabetes 
To examine the association between moderate drinking, cognitive function, and cognitive decline in women with type 2 diabetes.
From 1995-2001, we assessed cognitive function in 1,698 women aged 71-80 years with type 2 diabetes in the Nurses' Health Study. Assessments were repeated twice at 2-year intervals. We used linear regression to estimate multivariable-adjusted mean differences in initial cognitive function and longitudinal models to estimate cognitive decline over 4 years, according to average alcohol intake between diagnosis with diabetes and the initial cognitive measurement.
At the initial assessment, the mean score on our test of general cognition was 0.31 (95% CI 0.02, 0.60) points higher in women who were moderate alcohol drinkers (those consuming 1.0-9.9 grams of alcohol, or about 1 drink, per day) compared with abstainers. However, moderate alcohol was not associated with cognitive decline. Higher alcohol consumption (10.0-30.0 grams of alcohol per day) was not associated with initial cognition or cognitive decline, although there was no apparent harm either.
Among women with type 2 diabetes, moderate alcohol was associated with better initial cognition, but not reduced rates of cognitive decline. Thus, we found no clear and consistent cognitive benefits of moderate alcohol in diabetes.
PMCID: PMC2748648  PMID: 19625098
Alcohol consumption; Cognitive function; Type 2 diabetes
15.  Dietary Fat Intake and Cognitive Decline in Women With Type 2 Diabetes 
Diabetes Care  2009;32(4):635-640.
Individuals with type 2 diabetes have high risk of late-life cognitive impairment, yet little is known about strategies to modify risk. Targeting insulin resistance and vascular complications—both associated with cognitive decline—may be a productive approach. We investigated whether dietary fat, which modulates glucose and lipid metabolism, might influence cognitive decline in older adults with diabetes.
Beginning in 1995–1999, we evaluated cognitive function in 1,486 Nurses' Health Study participants, aged ≥70 years, with type 2 diabetes; second evaluations were conducted 2 years later. Dietary fat intake was assessed regularly beginning in 1980; we considered average intake from 1980 (at midlife) through initial cognitive interview and also after diabetes diagnosis. We used multivariate-adjusted linear regression models to obtain mean differences in cognitive decline across tertiles of fat intake.
Higher intakes of saturated and trans fat since midlife, and lower polyunsaturated to saturated fat ratio, were each highly associated with worse cognitive decline in these women. On a global score averaging all six cognitive tests, mean decline among women in the highest trans fat tertile was 0.15 standard units worse than that among women in the lowest tertile (95% CI −0.24 to −0.06, P = 0.002); this mean difference was comparable with the difference we find in women 7 years apart in age. Results were similar when we analyzed diet after diabetes diagnosis.
These findings suggest that lower intakes of saturated and trans fat and higher intake of polyunsaturated fat relative to saturated fat may reduce cognitive decline in individuals with type 2 diabetes.
PMCID: PMC2660474  PMID: 19336640

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