Background

Studies have linked midlife and late-life cardiovascular risk factors (CVRFs) to cognitive function, yet little is known about CVRF exposure in early adulthood and subsequent cognitive function. In addition, most studies rely on single assessments of CVRFs, which may not accurately reflect long-term exposure. We sought to determine the association between cumulative exposure to CVRFs from early to middle adulthood and cognitive function at midlife.

Methods and results

In a prospective study of 3381 adults (age, 18-30 years at baseline) with 25 years of follow-up, we assessed cognitive function at year 25 (2010-2011) with the Digit Symbol Substitution Test, Stroop Test, and Rey Auditory Verbal Learning Test analyzed with standardized z scores. The primary predictor was 25-year cumulative exposure estimated by areas under the curve for resting systolic and diastolic blood pressures, fasting blood glucose, and total cholesterol. Higher cumulative systolic and diastolic blood pressures and fasting blood glucose were consistently associated with worse cognition on all 3 tests. These associations were significant primarily for exposures above recommended guidelines; cognitive test z scores were between 0.06 and 0.30 points less, on average, for each 1-SD increase in risk factor area under the curve after adjustment for age, race, sex, and education (P<0.05 for all). Fewer significant associations were observed for cholesterol.

Conclusions

Cumulative exposure to CVRFs from early to middle adulthood, especially above recommended guidelines, was associated with worse cognition in midlife. The meaning of this association and whether it warrants more aggressive treatment of CVRFs earlier in life require further investigation.

OBJECTIVE: To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function. RESEARCH DESIGN AND METHODS: Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 72-89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined. RESULTS: The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits. CONCLUSIONS: Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.

Background

Most research has focused on definitions and predictors of successful aging. However, racial/ethnic minorities are often under represented in this research. Given that the U.S. population is aging and becoming more racially diverse, we examined correlates of "successful aging," as defined by physical functioning and overall quality of life (QOL), among racial/ethnic minority women aged 80 years and older in the Women's Health Initiative.

Methods

Participants included 1,924 racial/ethnic minority women (African Americans, Asian/Pacific Islanders, Hispanic/Latinos, and American Indian/Alaskan Natives) 80 years of age and older who are enrolled in the Women's Health Initiative and have physical functioning data after turning 80 years of age. Analysis of covariance was used to examine between and within group differences in physical functioning and selfrated overall QOL for African Americans, Asian/Pacific Islanders, and Hispanic/Latinos.

Results

We found no significant differences in physical functioning between racial/ethnic minority groups in adjusted analyses. However, overall QOL was significantly different between racial/ethnic minority groups. Age, recreational physical activity, and overall selfrated health were independent correlates of physical functioning across racial/ethnic minority groups, whereas overall selfrated health was the only consistent correlate of overall QOL across the minority groups for the within minority group comparisons.

Conclusions

Between racial/ethnic minority group differences in physical functioning are largely explained by demographic, psychosocial, behavioral, and health-related variables. We found statistically significant differences in selfrated overall QOL between racial/ethnic minority groups.

Objective

To study how type 2 diabetes adversely affects brain volumes, changes in volume, and cognitive function.

Research design and methods

Regional brain volumes and ischemic lesion volumes in 1,366 women, aged 72-89 years, were measured with structural brain magnetic resonance imaging (MRI). Repeat scans were collected an average of 4.7 years later in 698 women. Cross-sectional differences and changes with time between women with and without diabetes were compared. Relationships that cognitive function test scores had with these measures and diabetes were examined.

Results

The 145 women with diabetes (10.6%) at the first MRI had smaller total brain volumes (0.6% less; P = 0.05) and smaller gray matter volumes (1.5% less; P = 0.01) but not white matter volumes, both overall and within major lobes. They also had larger ischemic lesion volumes (21.8% greater; P = 0.02), both overall and in gray matter (27.5% greater; P = 0.06), in white matter (18.8% greater; P = 0.02), and across major lobes. Overall, women with diabetes had slightly (nonsignificant) greater loss of total brain volumes (3.02 cc; P = 0.11) and significant increases in total ischemic lesion volumes (9.7% more; P = 0.05) with time relative to those without diabetes. Diabetes was associated with lower scores in global cognitive function and its subdomains. These relative deficits were only partially accounted for by brain volumes and risk factors for cognitive deficits.

Conclusions

Diabetes is associated with smaller brain volumes in gray but not white matter and increasing ischemic lesion volumes throughout the brain. These markers are associated with but do not fully account for diabetes-related deficits in cognitive function.

Background

The higher risk of heart failure (HF) in African-American and Hispanic women compared with white women is related to the higher burden of risk factors (RFs) in minorities. However, it is unclear if there are differences in the association between the number of RFs for HF and the risk of development of HF and death within racial/ethnic groups.

Methods and results

In the WHI (Women's Health Initiative; 1993-2010), African-American (n=11 996), white (n=18 479), and Hispanic (n=5096) women with 1, 2, or 3+ baseline RFs were compared with women with 0 RF within their respective racial/ethnic groups to assess risk of developing HF or all-cause mortality before and after HF, using survival analyses. After adjusting for age, socioeconomic status, and hormone therapy, the subdistribution hazard ratio (95% confidence interval) of developing HF increased as number of RFs increased (P<0.0001, interaction of race/ethnicity and RF number P=0.18)-African-Americans 1 RF: 1.80 (1.01-3.20), 2 RFs: 3.19 (1.84-5.54), 3+ RFs: 7.31 (4.26-12.56); Whites 1 RF: 1.27 (1.04-1.54), 2 RFs: 1.95 (1.60-2.36), 3+ RFs: 4.07 (3.36-4.93); Hispanics 1 RF: 1.72 (0.68-4.34), 2 RFs: 3.87 (1.60-9.37), 3+ RFs: 8.80 (3.62-21.42). Risk of death before developing HF increased with subsequent RFs (P<0.0001) but differed by racial/ethnic group (interaction P=0.001). The number of RFs was not associated with the risk of death after developing HF in any group (P=0.25; interaction P=0.48).

Conclusions

Among diverse racial/ethnic groups, an increase in the number of baseline RFs was associated with higher risk of HF and death before HF but was not associated with death after HF. Early RF prevention may reduce the burden of HF across multiple racial/ethnic groups.

Background

Most research has focused on definitions and predictors of successful aging. However, racial/ethnic minorities are often under represented in this research. Given that the U.S. population is aging and becoming more racially diverse, we examined correlates of "successful aging," as defined by physical functioning and overall quality of life (QOL), among racial/ethnic minority women aged 80 years and older in the Women's Health Initiative.

Methods

Participants included 1,924 racial/ethnic minority women (African Americans, Asian/Pacific Islanders, Hispanic/Latinos, and American Indian/Alaskan Natives) 80 years of age and older who are enrolled in the Women's Health Initiative and have physical functioning data after turning 80 years of age. Analysis of covariance was used to examine between and within group differences in physical functioning and selfrated overall QOL for African Americans, Asian/Pacific Islanders, and Hispanic/Latinos.

Results

We found no significant differences in physical functioning between racial/ethnic minority groups in adjusted analyses. However, overall QOL was significantly different between racial/ethnic minority groups. Age, recreational physical activity, and overall selfrated health were independent correlates of physical functioning across racial/ethnic minority groups, whereas overall selfrated health was the only consistent correlate of overall QOL across the minority groups for the within minority group comparisons.

Conclusions

Between racial/ethnic minority group differences in physical functioning are largely explained by demographic, psychosocial, behavioral, and health-related variables. We found statistically significant differences in selfrated overall QOL between racial/ethnic minority groups.

Background

Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.

Methods

In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.

Results

The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258).

Conclusions

The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.

Background

Depression is a heritable trait that exists on a continuum of varying severity and duration. Yet, the search for genetic variants associated with depression has had few successes. We exploit the entire continuum of depression to find common variants for depressive symptoms.

Methods

In this genome-wide association study, we combined the results of 17 population-based studies assessing depressive symptoms with the Center for Epidemiological Studies Depression Scale. Replication of the independent top hits (p<1×10(-5)) was performed in five studies assessing depressive symptoms with other instruments. In addition, we performed a combined meta-analysis of all 22 discovery and replication studies.

Results

The discovery sample comprised 34,549 individuals (mean age of 66.5) and no loci reached genome-wide significance (lowest p = 1.05×10(-7)). Seven independent single nucleotide polymorphisms were considered for replication. In the replication set (n = 16,709), we found suggestive association of one single nucleotide polymorphism with depressive symptoms (rs161645, 5q21, p = 9.19×10(-3)). This 5q21 region reached genome-wide significance (p = 4.78×10(-8)) in the overall meta-analysis combining discovery and replication studies (n = 51,258).

Conclusions

The results suggest that only a large sample comprising more than 50,000 subjects may be sufficiently powered to detect genes for depressive symptoms.