Little is known regarding factors associated with soluble amyloid beta peptide (Aβ) concentrations in humans at late midlife, when Aβ is likely most critical to Alzheimer disease pathogenesis. We examined the association between insulin, insulin-related factors, and plasma Aβ at late midlife. Plasma Aβ42, Aβ40, fasting insulin, and c-peptide were measured in 468 women without diabetes, aged 59–69 years (median 63 years). Prior to blood draw, participants reported body mass index, waist circumference, physical activity, alcohol intake, hypertension, and diabetes family history. Linear regression was used to calculate age-adjusted mean differences in Aβ42 to Aβ40 ratio, and Aβ42 levels, by insulin and insulin-related factors. The ratio of Aβ42 to Aβ40 was statistically significantly lower in women with diabetes family history, and Aβ42 was significantly lower with less physical activity, greater waist circumference, hypertension, and diabetes family history (p<0.05 for all). Aβ42 to Aβ40 ratio, and Aβ42 levels, appeared lower with higher c-peptide levels (p-trend=0.07 and 0.06, respectively), although these were not statistically significant. In summary, insulin-related factors appear associated with lower plasma Aβ42 to Aβ40 ratio, and Aβ42, at late mid-life, consistent with increased brain sequestration of Aβ42 (relative to Aβ40), suggesting insulin merits focus in strategies to prevent dementia.

Background

Associations between postmenopausal hormone therapy (HT) and cognitive decline may depend on apolipoprotein E (APOE) status or timing of initiation.

Methods

We included 16,514 Nurses’ Health Study participants aged 70–81 years who were followed since 1976 and completed up to three telephone cognitive assessments (2 years apart), between 1995 and 2006. The tests assessed general cognition (Telephone Interview of Cognitive Status (TICS)), verbal memory, and category fluency. We used longitudinal analyses to estimate differences in cognitive decline across hormone groups. APOE genotype was available in 3697 participants.

Results

Compared with never users, past or current HT users showed modest but statistically significant worse rates of decline in the TICS: the multivariable-adjusted difference in annual rate of decline in the TICS among current estrogen only users versus never users was −0.04 (95% CI = −0.07, −0.004); for current estrogen+progestin users, the mean difference was −0.05 (95% CI = −0.10, −0.002). These differences were equivalent to those observed in women who are 1–2 years apart in age. We observed no protective associations with early timing of hormone initiation. We found suggestive interactions with APOE e4 status (e.g., on TICS, p-interaction = 0.10), where the fastest rate of decline was observed among APOE e4 carriers who were current HT users.

Conclusion

Regardless of timing of initiation, HT may be associated with worse rates of decline in general cognition, especially among those with an APOE e4 allele.

Background

High homocysteine levels may be neurotoxic and contribute to cognitive decline in older persons.

Objective

Examine the effect of supplementation with folic acid, vitamin B12 and vitamin B6 on cognitive change among women with cardiovascular disease (CVD) or CVD risk factors.

Design

The Women's Antioxidant and Folic Acid Cardiovascular Study is a randomized, placebo-controlled trial to test a combination of B vitamins (folic acid 2.5 mg, vitamin B6 50 mg, and vitamin B12 1 mg, daily) for secondary prevention of CVD. Randomization took place among 5,442 female health professionals, 40+ years, with CVD or at least three coronary risk factors in 1998 (after folic acid fortification began in the US). Shortly after randomization (mean=1.2 years), a cognitive function substudy was initiated among 2009 participants aged 65+ years. Telephone cognitive function testing was administered up to four times over 5.4 years with 5 tests of general cognition, verbal memory and category fluency. Repeated measures analyses were conducted. The primary outcome was a global composite score averaging all tests.

Results

Mean cognitive change from baseline did not differ between the B vitamin and placebo groups (difference in change in global score= 0.03, 95% CI −0.03, 0.08; p=0.30). However, supplementation appeared to confer benefits in preserving cognition among women with low baseline dietary intake of B vitamins.

Conclusions

Combined B vitamin supplementation did not delay cognitive decline among women with CVD or CVD risk factors. Possible cognitive benefits of supplementation among women with low dietary intake of B vitamins warrant further study.

Background

Individuals with vascular disease or risk factors have substantially higher rates of cognitive decline, yet little is known on means of maintaining cognition in this group.

Methods

We examined the relation between physical activity and cognitive decline in participants of the Women’s Antioxidant Cardiovascular Study (WACS), a cohort of women with prevalent vascular disease or ≥3 coronary risk factors. Recreational physical activity was assessed at baseline (1995–1996) and every two years thereafter. In 1998–2000, participants aged ≥65 years underwent a telephone cognitive battery including five tests of global cognition, verbal memory, and category fluency (n=2809). Tests were administered three additional times over 5.4 years. We used multivariable-adjusted generalized linear models for repeated measures to compare the annual rates of cognitive score changes across levels of total physical activity and on walking, as assessed at WACS baseline.

Results

We found a significant trend (p-trend<0.001) of slower rates of cognitive decline with increasing energy expenditure. Compared to the bottom quintile of total physical activity, significant differences in rates of cognitive decline were observed from the fourth quintile (p=0.04 for fourth quintile, p<0.001 for fifth quintile) or the equivalent of daily 30-minute walks at a brisk pace. This difference was equivalent to the difference in cognitive decline observed for women who were younger by 5–7 years. Walking was also strongly related to slower rates of cognitive decline (p-trend=0.003).

Conclusions

Regular physical activity, including walking, was associated with better preservation of cognitive function in older women with vascular disease or risk factors.

Objective

We investigated the relation between total fluid intake and incident urinary incontinence in the Nurses’ Health Study cohorts.

Study Design

We measured daily fluid intake using food frequency questionnaires among 65,167 women, aged 37–79 years, without urinary incontinence at study baseline (2000–2001). Women reported incontinence incidence on questionnaires during 4 years of follow-up. Multivariable-adjusted hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards models.

Results

We found no association between total fluid intake and risk of incident incontinence (hazard ratio 1.04, 95% confidence interval 0.98–1.10 comparing top versus bottom quintile of fluid intake). In analyses of incontinence type, total fluid intake was not associated with risks of incident stress, urgency, or mixed incontinence.

Conclusion

No significant risk of incident urinary incontinence was found with higher fluid intake in women. These findings suggest that women should not restrict their fluid intake to prevent incontinence development.

Purpose

Although caffeine consumption is common, and is generally believed to affect bladder function, little is known regarding caffeine intake and incident urinary incontinence.

Materials and Methods

We conducted a prospective cohort study of 65,176 women without incontinence, aged 37–79 years, in the Nurses’ Health Studies. Incident incontinence was identified from questionnaires, during 4 years of follow-up. Caffeine intake was measured using food frequency questionnaires administered prior to incontinence development. Multivariable-adjusted relative risks for the relation between caffeine intake and incontinence risk were calculated, as well as attributable risks.

Results

Caffeine was not associated with incontinence monthly or more, but there was a modest, significantly increased risk of incontinence at least weekly among women with the highest versus the lowest intake (RR 1.19, 95% CI 1.06–1.34, comparing >450 vs. <150 mg/day) and a significant trend of increasing risk with increasing intake (p-value for trend=0.01). This risk appeared focused in incident urgency incontinence (RR 1.34, 95% CI 1.00–1.80 comparing >450 vs. <150 mg/day, p-value for trend=0.05), but not stress or mixed incontinence (p-values for trend=0.75 and 0.19, respectively). The attributable risk for urgency incontinence associated with high caffeine intake was 25%.

Conclusions

Our findings suggest that high caffeine intake, but not lower levels, is associated with a modest increase in incidence of frequent urgency incontinence; one-quarter of these cases among women with the highest level of caffeine consumption might be eliminated if high caffeine intake was eliminated. Confirmation of these findings in other studies is needed before recommendations can be made.

Background

Growing evidence suggests that urinary incontinence prevalence and incidence in women vary by race. However, little is known regarding potential racial differences in remission and progression of incontinence, which would have meaningful implications for clinicians who treat incontinence.

Objective

To compare changes in incontinence frequency over two years among Asian, black, and white women with incontinence.

Methods

Participants in the Nurses’ Health Study cohorts provided information on their race and incontinence frequency on mailed questionnaires. Prospective analyses over two years of follow-up included 57,900 women aged 37–79 years with at least monthly incontinence at baseline.

Results

Changes in incontinence frequency appeared to vary by race, even after adjusting for a large variety of risk factors for incontinence. Specifically, compared with white women, black women were more likely to report no incontinence at follow-up (14% remission in black women vs. 9% in white women). Asian women were more likely to report any decrease in incontinence frequency (40% improvement in Asian women vs. 31% in white women). Incontinence improvement was also more common in black versus white women in analyses restricted to older women, although reports of improvement were similar among black and white women aged 54 years and younger. Black women were less likely to report a higher frequency of incontinence at follow-up (30% progression in black women vs. 34% in white women), and this difference was borderline statistically significant.

Conclusions

Higher odds of incontinence remission in black women, and improvement in Asian American women, compared with white women, may account for some of the previously observed differences in incontinence prevalence across racial groups, and were independent of health and lifestyle factors. Although incontinence is a common condition in women of all races, clinicians should be aware that the natural history of incontinence may differ across racial groups.

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.

OBJECTIVES

To examine the association between the type and number of subjective memory complaints (SMCs) and performance on objective cognitive tests.

DESIGN

Cross-sectional.

SETTING

Nurses’ Health Study.

PARTICIPANTS

Sixteen thousand nine hundred sixty-four women (mean age 74) who provided information on SMCs.

MEASUREMENTS

Telephone cognitive assessments and seven questions regarding SMCs were administered. Cognitive impairment was defined as a score of less than 31 on the Telephone Interview for Cognitive Status (TICS) and below the 10th percentile on other cognitive measures. To assess associations with SMCs, multivariable logistic regression was used to calculate odds ratios for cognitive impairment and multivariable linear regression to calculate mean differences in cognitive test scores, adjusting for age and depressive symptoms.

RESULTS

Some SMCs, such as trouble following a group conversation or finding one’s way around familiar streets, were more highly associated than others with odds of cognitive impairment. The complaint of forgetting things from one second to the next, generally considered part of normal aging, was not associated with cognitive impairment. In addition, there were strong, linear trends of increasingly worse scores on cognitive tests with increasing numbers of memory complaints. For each additional SMC endorsed, the odds of cognitive impairment increased approximately 20% when each SMC was weighted equally.

CONCLUSION

SMCs are associated with objective cognitive status and may be considered by primary care physicians in determining whether follow-up is warranted.

Objective To examine the hypothesis that mid-life adiposity is associated with a reduced probability of maintaining an optimal health status among those who survive to older ages.

Design Prospective cohort study.

Setting The Nurses’ Health Study, United States.

Participants 17 065 women who survived until at least the age of 70, provided information on occurrence of chronic disease, cognitive function, physical function, and mental health at older ages, and were free from major chronic diseases at mid-life (mean age was 50 at baseline in 1976).

Main outcome measures Healthy survival to age 70 and over was defined as having no history of 11 major chronic diseases and having no substantial cognitive, physical, or mental limitations.

Results Of the women who survived until at least age 70, 1686 (9.9%) met our criteria for healthy survival. Increased body mass index (BMI) at baseline was significantly associated with linearly reduced odds of healthy survival compared with usual survival, after adjustment for various lifestyle and dietary variables (P<0.001 for trend). Compared with lean women (BMI 18.5-22.9), obese women (BMI ≥30) had 79% lower odds of healthy survival (odds ratio 0.21, 95% confidence interval 0.15 to 0.29). In addition, the more weight gained from age 18 until mid-life, the less likely was healthy survival after the age of 70. The lowest odds of healthy survival were among women who were overweight (BMI ≥25) at age 18 and gained ≥10 kg weight (0.18, 0.09 to 0.36), relative to women who were lean (BMI 18.5-22.9) and maintained a stable weight.

Conclusions These data provide evidence that adiposity in mid-life is strongly related to a reduced probability of healthy survival among women who live to older ages, and emphasise the importance of maintaining a healthy weight from early adulthood.

Using the Nurses' Health Study, Qi Sun and colleagues examine whether moderate alcohol intake is associated with overall health and well-being among women who survive to older age.

Background

Observational studies have documented inverse associations between moderate alcohol consumption and risk of premature death. It is largely unknown whether moderate alcohol intake is also associated with overall health and well-being among populations who have survived to older age. In this study, we prospectively examined alcohol use assessed at midlife in relation to successful ageing in a cohort of US women.

Methods and Findings

Alcohol consumption at midlife was assessed using a validated food frequency questionnaire. Subsequently, successful ageing was defined in 13,894 Nurses' Health Study participants who survived to age 70 or older, and whose health status was continuously updated. “Successful ageing” was considered as being free of 11 major chronic diseases and having no major cognitive impairment, physical impairment, or mental health limitations. Analyses were restricted to the 98.1% of participants who were not heavier drinkers (>45 g/d) at midlife. Of all eligible study participants, 1,491 (10.7%) achieved successful ageing. After multivariable adjustment of potential confounders, light-to-moderate alcohol consumption at midlife was associated with modestly increased odds of successful ageing. The odds ratios (95% confidence interval) were 1.0 (referent) for nondrinkers, 1.11 (0.96–1.29) for ≤5.0 g/d, 1.19 (1.01–1.40) for 5.1–15.0 g/d, 1.28 (1.03–1.58) for 15.1–30.0 g/d, and 1.24 (0.87–1.76) for 30.1–45.0 g/d. Meanwhile, independent of total alcohol intake, participants who drank alcohol at regular patterns throughout the week, rather than on a single occasion, had somewhat better odds of successful ageing; for example, the odds ratios (95% confidence interval) were 1.29 (1.01–1.64) and 1.47 (1.14–1.90) for those drinking 3–4 days and 5–7 days per week in comparison with nondrinkers, respectively, whereas the odds ratio was 1.10 (0.94–1.30) for those drinking only 1–2 days per week.

Conclusions

These data suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health status among women who survive to older ages.

Please see later in the article for the Editors' Summary

Editors' Summary

Background

People have always drunk alcoholic beverages but throughout history there have been arguments about the risks and benefits of beer, wine, and spirits. It is clear that excessive alcohol use—heavy drinking (an average of more than two drinks per day for men or more than one drink per day for women; in the US, a “drink” is defined as 15 g of alcohol or, roughly speaking, a can of beer or a small glass of wine) or binge drinking (five or more drinks on a single occasion for men; 4 or more drinks at one time for women)—is harmful. It causes liver damage and increases the risk of developing some types of cancer. It contributes to depression and violence and interferes with relationships. And it is often implicated in fatal traffic accidents. However, in contrast to these and other harms associated with excessive alcohol use, moderate alcohol consumption seems to reduce the risk of specific diseases such as heart disease, stroke, and cognitive decline (deterioration in learning, reasoning, and perception).

Why Was This Study Done?

Although people who drink moderate amounts of alcohol have a reduced risk of premature death compared to abstainers or heavy drinkers, it is not known whether moderate alcohol consumption is associated with overall health among ageing populations. In many countries, elderly people are an increasingly large part of the population, so it is important to know how moderate alcohol consumption affects their well-being. In this study, the researchers examine the effect of alcohol consumption at midlife on successful ageing among the participants of the Nurses' Health Study. The researchers study the effect of midlife alcohol consumption because the chronic conditions that affect elderly people develop slowly and it is likely that factors in earlier life determine health in later life. Successful ageing is defined as being free of major chronic diseases such as cancer and heart disease, and having no major cognitive impairment, physical impairment, or mental health problems. The Nurses' Health Study enrolled 121,700 female registered nurses in 1976 to investigate the long-term effects of oral contraceptive use but has provided insights into many aspects of health and disease.

What Did the Researchers Do and Find?

The researchers assessed the alcohol consumption of the study participants at midlife (average age 58 years) from food frequency questionnaires completed in 1980 and 1984. Successful ageing for 13,984 participants who survived past 70 years was assessed by analyzing biennial health status questionnaires and cognitive function test results. One tenth of the women achieved successful ageing. After allowing for other factors that might affect their health such as smoking, women who drank light or moderate amounts of alcohol had a modestly increased chance of successful ageing compared to nondrinkers. For example, compared to nondrinkers, women who drank 5–15 g of alcohol per day (between one-third and one drink per day) had about a 20% higher chance of successful ageing. Independent of total alcohol intake, women who drank alcohol regularly had a better chance of successful ageing than occasional drinkers. Thus, compared to nondrinkers, women who drank five to seven days a week had nearly a 50% greater chance of successful ageing whereas women who drank only one or two days a week had a similar likelihood of successful ageing.

What Do These Findings Mean?

These findings suggest that regular, moderate consumption of alcohol at midlife may be related to a modest increase in overall health among women who survive to older ages. Because this is an observational study, it is possible that the women who drank moderately share other unknown characteristics that are actually responsible for their increased chance of successful ageing. Moreover, because all the study participants were women and most had European ancestry, these findings cannot be applied to men or to other ethnic groups. Nevertheless, these findings provide support for the 2010 US Department of Agriculture dietary guidelines, which state that consumption of up to one alcoholic drink per day for women and up to two alcoholic drinks per day for men may provide health benefits. Importantly, they also suggest that drinking alcohol regularly in moderation rather than occasional heavy drinking may be associated with a greater likelihood of successful ageing.

Additional Information

Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001090.

The US National Institute on Alcohol Abuse and Alcoholism has detailed information about alcohol and its effects on health, including a fact sheet on women and alcohol and a booklet entitled Alcohol, a woman's health issue

The US Centers for Disease Control and Prevention has a website on alcohol and public health

The UK National Health Service Choices website provides detailed information about drinking and alcohol, including how to calculate consumption

The Nutrition Source, a website maintained by the Department of Nutrition at Harvard School of Public Health, has an article entitled Alcohol: balancing risks and benefits

MedlinePlus provides links to many other resources on alcohol and on seniors' health

Details of the Nurses' Health Study are available

The 2010 US Department of Agriculture dietary guidelines are available

Objective

To prospectively study the relation between menopause, postmenopausal hormone use and risk of gout, since female sex hormones have been postulated to decrease gout risk among women.

Methods

In the Nurses’ Health Study, we examined the association between menopause, age at menopause, postmenopausal hormone use and risk of self-reported physician diagnosed incident gout among 92,535 women without gout at baseline. We used multivariate proportional hazards regression analysis to adjust for other risk factors for gout such as age, body mass index, diuretic use, hypertension, alcohol intake and dietary factors.

Results

During 16 years of follow-up (1,240,231 person-years), we documented 1,703 incident gout cases. The incidence rate of gout increased from 0.6 per 1000 person-years in women <45 years of age to 2.5 in women ≥75 years of age (p for trend<0.001). Compared with premenopausal women, postmenopausal women had a higher risk of incident gout (multivariate-adjusted relative risk [RR], 1.26; 95% Confidence Interval [CI], 1.03 to 1.55). Among women with natural menopause, women with age at menopause <45 years had a RR of 1.62 (95% CI, 1.12 to 2.33) of gout compared with women with age at menopause 50 to 54 years. Postmenopausal hormone users had a reduced risk of gout (RR, 0.82; 95% CI, 0.70 to 0.96).

Conclusion

These prospective findings indicate that menopause increases the risk of gout, whereas postmenopausal hormone therapy modestly reduces gout risk.

OBJECTIVE

To study consumption of major dietary antioxidants in relation to long-term risk of dementia.

DESIGN AND SETTING

The Rotterdam Study, a population-based, prospective cohort study in the Netherlands.

PARTICIPANTS

A total of 5,395 participants, aged 55+ years, who were free of dementia and provided dietary information at study baseline.

MAIN OUTCOME MEASURES

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.

RESULTS

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.

CONCLUSION

Higher intake of foods rich in vitamin E may modestly reduce long-term risk of dementia and AD.

Background/Objectives

Dietary fat intake may influence the rate of cognitive change among those at high risk due to vascular disease or risk factors.

Subjects/Methods

Women’s Antioxidant Cardiovascular Study began in 1995-96 as a randomized trial of antioxidants and B vitamin supplementation for secondary prevention in women with cardiovascular disease or ≥ 3 coronary risk factors. From 1998-99, eligible participants aged ≥ 65 years were administered a telephone cognitive battery including five tests of general cognition, memory and category fluency (n=2 551). Tests were administered four times over 5.4 years. The primary outcome was a global composite score averaging z-scores of all tests. Multivariable generalized linear models for repeated measures were used to evaluate the difference in cognitive decline rates across tertiles of total fat and various types of fat.

Results

Total fat intake or different types of fat were not related to cognitive decline. However, older age significantly modified the association: among the oldest participants, higher intakes of mono- and poly-unsaturated fat were inversely related to cognitive decline (p-interaction: 0.06 and 0.04, respectively), and the rate differences between the highest and lowest tertiles were cognitively equivalent to the rate differences observed with being 4-6 years younger.

Conclusions

In women at high risk of cognitive decline due to vascular disease or risk factors, dietary fat intake was not associated with 5-year cognitive change. However, a possible protective relation of unsaturated fats with cognitive decline in the oldest women warrants further study.

Background

Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline among healthy, community-dwelling older men without diabetes.

Methods

Fasting plasma insulin and C-peptide (insulin secretion) levels were measured in 1,353 nondiabetic men, aged 60–92 years (mean = 71.3 years), in the Physicians’ Health Study II, who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range = 1.5–4.0 years) using telephone-based tests (general cognition, verbal memory and category fluency). Primary outcomes were the Telephone Interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging 4 verbal tests). Multivariable linear regression models were used to estimate the relations of insulin and C-peptide to cognitive decline.

Results

Higher fasting insulin was associated with a greater decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency, e.g. the multivariable-adjusted mean difference (95% CI) in decline for men with the highest versus lowest insulin levels was −0.62 (−1.15, −0.09) points on the TICS (p for trend = 0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was a greater decline across all tests with increasing C-peptide, but the findings were statistically significant only for the global score (p for trend = 0.03).

Conclusions

Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.

Objective

We calculated incidence rates of urinary incontinence by incontinence frequency and type over 4 years in Asian, black, and white women in the United States.

Study Design

Prospective analyses included 76,724 participants aged 37–79 years in the Nurses’ Health Study cohorts with no incontinence at baseline.

Results

The 4-year incidence of incontinence at least monthly was higher in white women (7.3/100 person-years) compared with Asian (5.7/100 person-years, p=0.003) and black women (4.8/100 person-years, p<0.001). The incidence of at least weekly stress incontinence was significantly lower in black compared with white women (0.1 versus 0.8 per 100 person-years, p<0.001). The difference between black and white women in the incidence of any incontinence and stress incontinence remained significant after adjusting for known risk factors (p<0.001 for both).

Conclusions

Urinary incontinence incidence differs by race. Studies to confirm these results and better understand underlying mechanisms are needed.

Background

Type 2 diabetes has been associated with diminished late-life cognition; less is known about relations of insulin levels and insulin secretion to cognitive change among persons without diabetes. We examined prospectively relations of fasting insulin levels and insulin secretion to cognitive decline, among healthy, community-dwelling older men without diabetes.

Methods

Fasting plasma insulin and c-peptide (insulin secretion) levels were measured in 1,353 non-diabetic men, aged 60–92 years (mean=71.3), in the Physicians’ Health Study II who participated in cognitive testing an average of 3.3 years later. Two assessments were administered 2 years apart (range=1.5–4.0) using telephone-based tests (general cognition, verbal memory, and category fluency). Primary outcomes were the Telephone interview for Cognitive Status (TICS), global cognition (averaging all tests) and verbal memory (averaging four verbal tests). Multivariable linear regression models were used to estimate relations of insulin and c-peptide to cognitive decline.

Results

Higher fasting insulin was associated with worse decline on all tests, after adjustment. Findings were statistically significant for the TICS and category fluency: e.g., the multivariable-adjusted mean difference (95% CI) in decline for men with the highest vs. lowest insulin levels was −0.62 (−1.15, −0.09) points on the TICS (p-trend=0.04); this difference was similar to that between men 7 years apart in age. Similarly, there was worse decline across all tests with increasing c-peptide, but findings were statistically significant only for global score (p-trend=0.03).

Conclusions

Higher fasting insulin and greater insulin secretion in older men may be related to overall cognitive decline, even in the absence of diabetes.

Dementia of the Alzheimer’s type (DAT) is a major public health threat in developed countries where longevity has been extended to the eighth decade of life. Estimates of prevalence and incidence ofDAT vary with what is measured, be it change from a baseline cognitive state or a clinical diagnostic endpoint, such as Alzheimer’s disease. Judgment of what is psychometrically “normal” at the age of 80 years implicitly condones a decline from what is normal at the age of 30. However, because cognitive aging is very heterogeneous, it is reasonable to ask “Is ‘normal for age’ good enough to screen forDAT or its earlier precursors of cognitive impairment?” Cost containment and accessibility of ascertainment methods are enhanced by well-validated and reliable methods such as screening for cognitive impairment by telephone interviews. However, focused assessment of episodic memory, the key symptom associated with DAT, might be more effective at distinguishing normal from abnormal cognitive aging trajectories. Alternatively, the futuristic “Smart Home,” outfitted with unobtrusive sensors and data storage devices, permits the moment-to-moment recording of activities so that changes that constitute risk for DAT can be identified before the emergence of symptoms.

Objective

To describe changes in urinary incontinence in middle-aged women.

Study Design

A prospective analysis of 64,650 women aged 36 to 55 years in the Nurses’ Health Study II. Participants reported urine leaking in 2001 and 2003. Among continent women, we estimated 2-year incidence proportions; among incontinent women, we estimated proportions with remission.

Results

The 2-year incidence of incontinence was 13.7%. Incidence generally increased through age 50 years, then declined slightly between ages 51 and 55 years. Among women with incident incontinence at least once per week, the 2-year incidence of stress incontinence was 1.7%; this incidence increased through age 50 years. The incidence of urge incontinence was stable across age groups (overall 2-year incidence=0.4%). Complete remission of symptoms occurred in 13.9% of women with incontinence at baseline; remission was more common in younger than older women.

Conclusion

In our study, both incident urinary incontinence and remission of symptoms were common.

Background

Physical activity is associated with reduced risks of chronic diseases and premature death. Whether physical activity is also associated with improved overall health among those who survive to older ages is unclear.

Methods

A total of 13,535 Nurses’ Health Study participants who were free of major chronic diseases at baseline in 1986 and had survived to age 70 years or older as of 1995–2001 comprised the study population. We defined successful survival as no history of 11 major chronic diseases and no cognitive impairment, physical impairment, or mental health limitations.

Results

After multivariate adjustment for covariates, higher physical activity levels at mid-life, as measured by metabolic equivalent tasks, were significantly associated with better odds of successful survival. Significant increases in successful survival were observed beginning at the third quintile of activity: Odds ratios (95% confidence interval) in the lowest to highest quintiles were 1.00 (reference), 0.98 (0.80, 1.20), 1.37 (1.13, 1.65), 1.34 (1.11, 1.61), and 1.99 (1.66, 2.38; P for trend < 0.0001). Increasing energy expenditure from walking was associated with a similar elevation in odds of successful survival: The odds ratios (95% confidence interval) of successful survival across quintiles of walking were 1.00 (reference), 0.99 (0.80, 1.21), 1.19 (0.97, 1.45), 1.50 (1.24, 1.82), and 1.47 (1.22, 1.79; P for trend < 0.0001).

Conclusion

These data provide evidence that higher levels of mid-life physical activity are associated with exceptional health status among women who survive to older ages, and corroborate the potential role of physical activity in improving overall health.

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.

Background

Plasma levels of the amyloid β-peptides (Aβ) are potential biomarkers of early cognitive impairment and decline, and of Alzheimer disease (AD) risk.

Objective

To relate mid-life plasma Aβ measures, and ten-year change in plasma Aβ since mid-life, to later-life cognitive decline.

Design, setting, participants

Plasma Aβ-40 and Aβ-42 levels were measured in 481 Nurses’ Health Study participants in late mid-life (mean age=63.6 years) and again 10 years later (mean age=74.6 years). Cognitive testing also began 10 years after the initial blood draw. Participants completed three repeated telephone-based assessments (average span=4.1 years). Multivariable linear mixed effects models were used to estimate relations of mid-life plasma Aβ-40:Aβ-42 ratios and Aβ-42 levels to later-life cognitive decline, and to relate ten-year change in Aβ-40:Aβ-42 and Aβ-42 to cognitive decline.

Main Outcome Measures

The primary outcomes were: the Telephone Interview for Cognitive Status (TICS); a global score averaging all tests (TICS, immediate and delayed verbal recall, category fluency, and attention); and a verbal memory score averaging four tests of verbal recall.

Results

Higher mid-life plasma Aβ-40:Aβ-42 ratio was associated with worse later-life decline on the global score (p-trend=0.04). Furthermore, an increase in Aβ-40:Aβ-42 since mid-life predicted greater decline on the global score (p-trend=0.03) and the TICS (p-trend=0.02). There was no association between mid-life plasma Aβ-42 levels alone – or change in Aβ-42 since mid-life – and cognitive decline.

Conclusions

In this large community-dwelling sample, higher plasma Aβ-40:Aβ-42 ratios in late mid-life, and increases in Aβ-40:Aβ-42 ten years later, were significantly associated with greater decline in global cognition at late-life.

Aims:

To examine the association between moderate drinking, cognitive function, and cognitive decline in women with type 2 diabetes.

Methods:

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.

Results:

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.

Conclusions:

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.

Background

Cardiovascular factors are associated with cognitive decline. Antioxidants may be beneficial.

Methods

The Women’s Antioxidant Cardiovascular Study was a trial of vitamin E (402 mg every other day), β-carotene (50 mg every other day) and vitamin C (500 mg daily) for the secondary prevention of cardiovascular disease (CVD). From 1995–1996, women 40+ years, with CVD or ≥3 coronary risk factors were randomized. From 1998–1999, a cognitive function substudy was initiated among 2824 participants aged 65+ years. With 5 cognitive tests, cognition was assessed by telephone four times over 5.4 years. The primary outcome was a global composite score averaging all scores; repeated measures analyses were used to examine cognitive change over time.

Results

Vitamin E and β-carotene supplementation were not associated with slower rates of cognitive change (mean difference in change for vitamin E versus placebo = −0.01, 95% CI −0.05, 0.04, p=0.78; for β-carotene=0.03, 95% CI −0.02, 0.07, p=0.28). Although vitamin C supplementation was associated with better performance at the last assessment (mean difference = 0.13, 95% CI 0.06, 0.20, p=0.0005), it was not associated with cognitive change over time (mean difference in change = 0.02, 95% CI −0.03, 0.07, p=0.39). Vitamin C was more protective against cognitive change among those with new cardiovascular events during the trial (p-interaction= 0.009).

Conclusions

Antioxidant supplementation did not slow cognitive change among women with preexisting CVD or CVD risk factors. A possible late effect of vitamin C or of β-carotene among those with low dietary intake on cognition warrant further study.

Purpose

Recent data in postmenopausal women indicate that current and past use of exogenous hormones is related to urinary incontinence (UI) risk. Little is known about exogenous hormones and UI risk in younger women. We investigated the association between oral contraceptive pills (OCPs) and incident UI in premenopausal women enrolled in the Nurses' Health Study II.

Materials and Methods

Participants reported use of OCPs from 1989 to 2001. Among 21,864 premenopausal women, aged 37-54 years, reporting no UI in 2001, we identified 749 cases with incident UI at least weekly between 2001 and 2003. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression.

Results

Women who had ever used OCPs had statistically significant 27% (95% CI 1-59%) increased odds of developing UI at least weekly compared with women who never used OCPs. Among women with 10 or more years of use, the odds ratio increased to 1.48 (95% CI 1.13-1.95). Ever use of OCPs was specifically associated with urgency UI (OR 2.48, 95% CI 1.07-5.76) and not stress UI (OR 1.04, 95% CI 0.78-1.40). Although we had limited information on urinary tract infection, control for urinary tract infection did not alter these findings.

Conclusions

Use of OCPs may be associated with a modest increase in odds of UI among premenopausal women. However, this is one of the first reports of such an association and thus, further research is needed to confirm our findings and investigate possible mechanisms.