Search

ObjectiveTo determine associations of alcohol use with cognitive aging among middle-aged men.Method1,608 male twins (mean 57 years at baseline) participated in up to three visits over 12 years, from 2003-2007 to 2016-2019. Participants were classified into six groups based on current and past self-reported alcohol use: lifetime abstainers, former drinkers, very light (1-4 drinks in past 14 days), light (5-14 drinks), moderate (15-28 drinks), and at-risk drinkers (>28 drinks in past 14 days). Linear mixed-effects regressions modeled cognitive trajectories by alcohol group, with time-based models evaluating rate of decline as a function of baseline alcohol use, and age-based models evaluating age-related differences in performance by current alcohol use. Analyses used standardized cognitive domain factor scores and adjusted for sociodemographic and health-related factors.ResultsPerformance decreased over time in all domains. Relative to very light drinkers, former drinkers showed worse verbal fluency performance, by -0.21 SD (95% CI -0.35, -0.07), and at-risk drinkers showed faster working memory decline, by 0.14 SD (95% CI 0.02, -0.20) per decade. There was no evidence of protective associations of light/moderate drinking on rate of decline. In age-based models, light drinkers displayed better memory performance at advanced ages than very light drinkers (+0.14 SD; 95% CI 0.02, 0.20 per 10-years older age); likely attributable to residual confounding or reverse association.ConclusionsAlcohol consumption showed minimal associations with cognitive aging among middle-aged men. Stronger associations of alcohol with cognitive aging may become apparent at older ages, when cognitive abilities decline more rapidly.

We examined whether the often-reported protective association of alcohol with cardiovascular disease (CVD) risk could arise from confounding. Our sample comprised 908 men (56−67 years), free of prevalent CVD. Participants were categorized into 6 groups: never drinkers, former drinkers, and very light (1−4 drinks in past 14 days), light (5−14 drinks), moderate (15−28 drinks), and at-risk (>28 drinks) drinkers. Generalized linear mixed effect models examined the associations of alcohol use with three established CVD risk scores: The Framingham Risk Score (FRS); the atherosclerotic CVD (ASCVD) risk score; and the Metabolic Syndrome (MetS) Severity score, adjusting for group differences in demographics, body size, and health-related behaviors. In separate models we additionally adjusted for several groups of potentially explanatory factors including socioeconomic status, social support, physical and mental health status, childhood factors, and prior history of alcohol misuse. Results showed lower CVD risk among light and moderate alcohol drinkers, relative to very light drinkers, for all CVD risk scores, independent of demographics, body size, and health-related behaviors. Alcohol-CVD risk associations were robust to further adjustment for several groups of potential explanatory factors. Study limitations include the all-male sample with limited racial and ethnic diversity, and the inability to adjust for sugar consumption and for patterns of alcohol consumption. Although this observational study does not address causation, results show that middle-aged men who consume alcohol in moderation have lower CVD risk and better cardiometabolic health than men who consume little or no alcohol, independent of a variety of health, behavioral, psychosocial, and earlier life factors.

Midlife vascular disease increases risk for dementia and effects of vascular dysfunction on brain health differ between men and women. Elevated pulse pressure, a surrogate for arterial stiffness, contributes to cerebrovascular pathology and white matter damage that may advance cognitive aging; however, it remains unclear how associations between pulse pressure and neural integrity differ by sex and age. This study used restriction spectrum imaging to examine associations between pulse pressure and brain microstructure in community-dwelling women (N=88) and men (N=55), aged 56 to 97 (mean, 76.3) years. Restricted isotropic (presumed intracellular), hindered isotropic (presumed extracellular), neurite density, and free water diffusion were computed in white matter tracts and subcortical regions. After adjustment for age and sex, higher pulse pressure correlated with lower restricted isotropic diffusion in global white matter, with more pronounced associations in parahippocampal cingulum, as well as in thalamus and hippocampus. Subgroup analyses demonstrated stronger correlations between pulse pressure and restricted isotropic diffusion in association fibers for participants ≤75 years than for older participants, with stronger effects for women than men of this age group. Microstructure in parahippocampal cingulum and thalamus differed by pulse pressure level regardless of antihypertensive treatment. Increased pulse pressure may lead to widespread injury to white matter and subcortical structures, with greatest vulnerability for women in late middle to early older age. Restriction spectrum imaging could be useful for monitoring microstructural changes indicative of neuronal loss or shrinkage, demyelination, or inflammation that accompany age-related cerebrovascular dysfunction.

BackgroundReduced kidney function has been associated with cognitive decline. Most studies have examined a single marker of kidney function and have limited duration of follow-up.ObjectiveThis study evaluated associations between markers of kidney function (urine albumin, estimated glomerular filtration rate [eGFR], and hyperuricemia) with cognitive performance over time.MethodsThis is a longitudinal study of 1,634 community-dwelling adults (mean age = 71.7 years), with kidney function markers and cognitive ability measured at baseline (1992-1996) and at up to five additional time points with a maximum of 23.4 years (mean = 8.1 years) of follow-up. Associations between kidney function and cognitive performance were assessed using linear mixed effects models. Testing for interaction by sex was conducted.ResultsAlbuminuria (urine albumin-to-creatinine ratio [ACR]≥30 mg/g) was associated with steeper annual declines in global cognitive function (MMSE, β= -0.12, p = 0.003), executive function (Trails B, β= 4.50, p

ContextObservational studies show discordant links between endogenous testosterone levels and cardiovascular diseases (CVD).ObjectiveWe assessed whether sex hormones and sex hormone-binding globulin (SHBG) are associated with CVD in community-dwelling elderly men.Design setting and participantsProspective study of incident CVD among 552 men ≥ 65 years in the MrOS Sleep Study without prevalent CVD and no testosterone therapy at baseline.OutcomesFasting serum levels of total testosterone and estradiol were measured using liquid chromatography-mass spectrometry, and SHBG by chemiluminescent substrate. The association of sex hormones and SHBG with incident coronary heart disease (CHD), cerebrovascular (stroke and transient ischemic attack) and peripheral arterial disease (PAD) events were assessed by quartile and per SD increase in proportional hazards models.ResultsAfter 7.4 years, 137 men (24.8%) had at least 1 CVD event: 90 CHD, 45 cerebrovascular and 26 PAD. The risk of incident CVD events was not associated with quartiles of baseline sex hormones or SHBG (all P ≥ 0.16). For +1 SD in total testosterone, the multivariate-adjusted hazard ratio was 1.04 (95% CI, 0.80-1.34) for CHD, 0.86 (0.60-1.25) for cerebrovascular, and 0.81 (0.52-1.26) for PAD events. When analyzed as continuous variables or comparing highest to low quartile, levels of bioavailable testosterone, total estradiol, testosterone/estradiol ratio and SHBG were not associated with CVD events.ConclusionsIn community-dwelling elderly men, endogenous levels of testosterone, estradiol, and SHBG were not associated with increased risk of CHD, cerebrovascular, or PAD events. These results are limited by the small number of events and should be explored in future studies.

BackgroundHearing impairment is prevalent among older adults and has been identified as a risk factor for cognitive impairment and dementia. We evaluated the association of hearing impairment with long-term cognitive decline among community-dwelling older adults.MethodsA population-based longitudinal study of adults not using hearing aids who had hearing acuity and cognitive function assessed in 1992-1996, and were followed for a maximum of 24 years with up to five additional cognitive assessments. Hearing acuity was categorized based on pure-tone average (PTA) thresholds: normal (PTA ≤ 25 dB), mild impairment (PTA > 25-40 dB), moderate/severe impairment (PTA > 40 dB).ResultsOf 1,164 participants (mean age 73.5 years, 64% women), 580 (49.8%) had mild hearing impairment and 196 (16.8%) had moderate/severe hearing impairment. In fully adjusted models, hearing impairment was associated with steeper decline on the Mini-Mental State Examination (MMSE) (mild impairment β = -0.04, p = .01; moderate/severe impairment β = -0.08, p = .002) and Trails B (mild impairment β = 1.21, p = .003; moderate/severe impairment β = 2.16, p = .003). Associations did not differ by sex or apolipoprotein E (APOE) ϵ4 status and were not influenced by social engagement. The MMSE-hearing association was modified by education: mild hearing impairment was associated with steeper decline on the MMSE among participants without college education but not among those with college education. Moderate/severe hearing impairment was associated with steeper MMSE decline regardless of education level.ConclusionsHearing impairment is associated with accelerated cognitive decline with age, and should be screened for routinely. Higher education may provide sufficient cognitive reserve to counter effects of mild, but not more severe, hearing impairment.

Backgroundphysical activity in older age has been associated with better cognitive function, but the role of earlier life physical activity is less well understood.Objectivedetermine associations between physical activity throughout the lifespan and cognitive function in older age.Designcross-sectional study.Settingthe Rancho Bernardo Study of Healthy Aging in southern California.SubjectsA total of 1,826 community-dwelling men and women (60-99 years) who attended a research visit in 1988-92.Methodsparticipants underwent cognitive testing at older age, and reported physical activity as a teenager, at age 30 years, 50 years and currently. For each time-point, participants were classified as regularly active (3+ times/week) or inactive.Resultsregular physical activity was associated with better cognitive function, with physical activity at older ages showing the strongest associations. Physical activity in older age was associated with better global cognitive function, executive function and episodic memory, regardless of intensity. Intense physical activity in teenage years was associated with better late-life global cognitive function in women. Teenage physical activity interacted with older age physical activity on executive function; those active at both periods performed better than those active at only one period. Similar patterns of associations were observed after excluding individuals with poor health.Conclusionsregular physical activity in older age, regardless of intensity, is associated with better cognitive function. Physical activity in teenage years may enhance cognitive reserve to protect against age-related decline in executive function. Further research is needed to assess the effect of physical activity across the lifespan on healthy brain ageing.

ObjectiveThe apolipoprotein E (APOE) gene is an established risk factor for sporadic Alzheimer's disease, with elevated risk for ε4-carriers and reduced risk for ε2-carriers. However, it is unclear whether APOE modifies risk for cognitive decline in normal aging. The objective of this study was to determine whether ε2 and ε4 are associated with rates of normal cognitive aging, and whether associations of ε4 with cognitive decline are modified by sex, education or health behaviors (exercise, alcohol consumption, smoking).MethodA community-based sample of 1,393 older adults were genotyped for APOE and underwent cognitive assessment up to seven times over a maximum of period of 27 years.Resultsε2-carriers showed slower executive function decline with age relative to ε3 homozygotes or ε4-carriers, whereas ε4-carriers demonstrated more rapid executive function and verbal fluency decline. Accelerated executive function decline was particularly pronounced in ε4-carriers with lower education. After excluding individuals with cognitive impairment, faster executive function decline was still apparent in ε4-carriers, and the effect of ε4 on episodic memory interacted with alcohol consumption, such that only ε4-carriers who did not drink showed more rapid memory decline than ε4 noncarriers. The influence of ε4 on cognitive aging did not differ by sex, nor was it modified by smoking or exercise.ConclusionsThese findings indicate that the ε2 and ε4 alleles have differential effects on cognitive aging, and that negative effects of ε4 may be partly mitigated by behavioral choices. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

BackgroundAlthough physical activity has been associated with better cognitive function and reduced dementia risk, its association with cognitive decline in normal aging remains uncertain.ObjectiveTo determine whether physical activity in youth and older age are associated with age-related cognitive change.MethodsOver a period of 27 years, 2,027 community-dwelling adults (mean age 73.5; 60% women) of the Rancho Bernardo Study of Healthy Aging completed up to seven cognitive assessments, including tests of global cognitive function, executive function, verbal fluency, and episodic memory. At each visit, participants reported concurrent physical activity. At baseline (1988- 1992), participants additionally reported physical activity as a teenager and at age 30. For each age period, participants were classified as regularly active (3+ times/week) or inactive.ResultsAssociations between concurrent physical activity and better cognitive function were stronger with advancing age on all tests, even after accounting for education, health, and lifestyle factors, as well as survival differences (ps  0.40). Individuals who were physically active at age 30 and older age maintained the highest global cognitive function with advancing age (p = 0.002).ConclusionRegular physical activity is associated with better cognitive function with advancing age. Physical activity in young adulthood may contribute to cognitive reserve, which together with physical activity in later years, may act to preserve cognitive function with age.

Background:This study investigated the effects of metformin and weight loss on biomarkers associated with breast cancer prognosis. Methods:Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomly assigned to metformin vs placebo and to a weight loss intervention vs control (ie, usual care). The 2 × 2 factorial design allows a single randomized trial to investigate the effect of two factors and interactions between them. Outcomes were changes in fasting insulin, glucose, C-reactive protein (CRP), estradiol, testosterone, and sex-hormone binding globulin (SHBG). The trial was powered for a main effects analysis of metformin vs placebo and weight loss vs control. All tests of statistical significance were two-sided. Results:A total of 313 women (94.0%) completed the six-month trial. High prescription adherence (ie, ≥80% of pills taken) ranged from 65.9% of participants in the metformin group to 81.3% of those in the placebo group (P < .002). Mean percent weight loss was statistically significantly higher in the weight loss group (-5.5%, 95% confidence interval [CI] = -6.3% to -4.8%) compared with the control group (-2.7%, 95% CI = -3.5% to -1.9%). Statistically significant group differences (ie, percent change in metformin group minus placebo group) were -7.9% (95% CI = -15.0% to -0.8%) for insulin, -10.0% (95% CI = -18.5% to -1.5%) for estradiol, -9.5% (95% CI = -15.2% to -3.8%) for testosterone, and 7.5% (95% CI = 2.4% to 12.6%) for SHBG. Statistically significant group differences (ie, percent change in weight loss group minus placebo group) were -12.5% (95% CI = -19.6% to -5.3%) for insulin and 5.3% (95% CI = 0.2% to 10.4%) for SHBG. Conclusions:As adjuvant therapy, weight loss and metformin were found to be a safe combination strategy that modestly lowered estrogen levels and advantageously affected other biomarkers thought to be on the pathway for reducing breast cancer recurrence and mortality.

Diet may be an important modifiable risk factor for maintenance of cognitive health in later life. This study aimed at examining associations between common dietary indices and dietary patterns defined by factor analysis and cognitive function in older community-dwelling adults. Dietary information for 1499 participants from the Rancho Bernardo Study was collected in 1988⁻1992 and used to calculate the alternate Mediterranean diet score, Alternate Healthy Eating Index (AHEI)-2010 score and factor scores derived from factor analysis of nutrients. Global cognitive function, executive function, verbal fluency and episodic memory were assessed at approximate four-year intervals from 1988⁻2016. Linear mixed models were used to examine associations between dietary patterns and cognitive trajectories. Estimates for the highest vs. lowest tertile in models adjusting for age, sex, education, energy intake, lifestyle variables and retest effect showed greater adherence to the Mediterranean score was associated with better baseline global cognitive function (β (95% CI) = 0.33 (0.11, 0.55)). The AHEI-2010 score was not significantly associated with cognitive performance. Higher loading on a plant polyunsaturated fatty acid (PUFA)/vitamin E factor was associated with better baseline global cognitive function and executive function (β = 0.22 (0.02, 0.42) and β = -7.85 (-13.20, -2.47)). A sugar/low protein factor was associated with poorer baseline cognitive function across multiple domains. Dietary patterns were not associated with cognitive decline over time. Adherence to a healthy diet with foods high in PUFA and vitamin E and a low sugar to protein ratio, as typified by a Mediterranean diet, may be beneficial for cognitive health in late life.

Purpose: To examine associations of prediagnosis high-sensitivity C-reactive protein (hsCRP) with breast cancer incidence and postdiagnosis survival and to assess whether associations are modified by body mass index (BMI).Methods: A prospective analysis of the Women's Health Initiative was conducted among 17,841 cancer-free postmenopausal women with baseline hsCRP measurements. Cox proportional hazards models were used to examine associations between hsCRP concentrations and (i) breast cancer risk (n cases = 1,114) and (ii) all-cause mortality after breast cancer diagnosis. HRs are per 1 SD in log hsCRP.Results: hsCRP was not associated with breast cancer risk overall [HR = 1.05; 95% confidence interval (CI), 0.98-1.12]; however, an interaction between BMI and hsCRP was observed (Pinteraction = 0.02). A 1 SD increase in log hsCRP was associated with 17% increased breast cancer risk (HR = 1.17; 95% CI, 1.03-1.33) among lean women (BMI < 25), whereas no association was observed among overweight/obese (BMI ≥ 25) women. Prediagnosis hsCRP was not associated with overall mortality (HR, 1.04; 95% CI, 0.88-1.21) after breast cancer diagnosis; however, an increased mortality risk was apparent among leaner women with higher hsCRP levels (HR, 1.39, 95% CI, 1.03-1.88).Conclusions: Prediagnosis hsCRP levels are not associated with postmenopausal breast cancer incidence or survival overall; however, increased risks are suggested among leaner women. The observed effect modification is in the opposite direction of a previous case-control study finding and warrants further investigation.Impact: Associations of higher CRP levels with incident breast cancer and survival after breast cancer may depend on BMI. Cancer Epidemiol Biomarkers Prev; 26(7); 1100-6. ©2017 AACR.

ObjectivePersons with diabetes have accelerated muscle loss. The association of fasting and postchallenge glucose levels per se to grip strength, a clinical marker of poor physical function, and potential sex differences in this relationship has not been previously described.DesignLongitudinal cohort.SettingUSA.ParticipantsParticipants were community-dwelling older adults (mean age 71.3 years) without self-reported diabetes and/or use of diabetes medication with glucose measured at baseline (1992-1996).MeasurementsFasting plasma glucose (FPG) was measured in 1019 women and 636 men. Two-hour glucose (2HG) levels after a 75 g oral glucose tolerance test were also available (women, n=870; men, n=559). Dominant hand grip strength was assessed using a hand-held dynamometer at 3.0±1.6 visits over a median 7.0 years. Mixed linear models examined the association of baseline glucose levels with grip strength, accounting for repeated visits, and adjusting for covariates.ResultsSex-specific FPG quartiles were associated with unadjusted differences in grip strength among women (p=0.03) but not men (p=0.50). However, in men, adjusting for age, education, height, weight, peripheral neuropathy, physical activity, and comorbidities, each SD (SD=17 mg/dL) higher FPG was associated with persistently lower grip strength (-0.44±0.22 kg, p=0.049); 2HG (SD=50 mg/dL) was unrelated to grip strength (-0.39±0.25 kg, p=0.13). In women, neither FPG (SD=16 mg/dL) nor 2HG (SD=45 mg/dL) was associated with grip strength (0.02±0.12 kg, p=0.90; and -0.20±0.14 kg, p=0.14; respectively) after adjustment. The rate of change in grip strength did not differ across FPG or 2HG quartiles in either sex.ConclusionsIn age-adjusted analyses, elevated fasting glucose levels are associated with persistently lower grip strength in older men, but not women. Future studies are needed to elucidate reasons for these sex differences and may provide further insight into accelerated loss of muscle function as a complication of diabetes in older adults.

ObjectiveWe examined the association between breastfeeding and postmenopausal visceral adiposity.MethodsParticipants were community-dwelling women aged 55-80 from the Caucasian Rancho Bernardo Study, the Filipino Women's Health Study, and the Health Assessment Study of African-American Women who had visceral adipose tissue (VAT) measurements by computed tomography between 2000 and 2002. Linear regression was used to determine the association between average breastfeeding duration per child and VAT.ResultsIn Caucasian, Filipino, and African-American women, average number of live births was 3, 4, and 3; average breastfeeding duration was 4.3, 1.8, and 5.1 months, respectively. Filipino women had more live births, were more likely to breastfeed, and breastfed shorter durations. African-American women had lower VAT, despite higher subcutaneous adipose tissue (SAT), BMI, and waist girth. Women who breastfed >3 months on average had 8.8 cm(3) lower VAT than women who breastfed ≤3 months, independent of covariates. Women who initiated breastfeeding had lower BMI and waist girth than those who did not, but they did not differ by VAT unless they breastfed >3 months. Associations were independent of race/ethnicity.ConclusionsResults suggest breastfeeding initiation is associated with reduced BMI and smaller waist girth, and breastfeeding >3 months is associated with lower postmenopausal VAT.

ObjectiveTo examine the association of abdominal muscle area with coronary artery calcium (CAC) presence, extent, and progression in a multi-ethnic cohort of older, community-dwelling post-menopausal women.Design and settingCross-sectional and longitudinal population-based cohort.ParticipantsThe sample comprised 179 non-Hispanic White women, 116 Filipina women and 144 African American women, all without known CVD, who underwent chest and abdominal computed tomography (CT) scans twice about four years apart for abdominal muscle and fat, as well as CAC.Main outcome measuresCAC presence, extent and progression.ResultsThere was a significant interaction of ethnicity with baseline oblique muscle area (p-for-interaction .01), and marginally significant interactions with baseline total and paraspinal muscle for change in CAC (p-for-interactions both .09). Among Filipina women, each standard deviation (SD) greater total muscle area was associated with a 26% (95% CI (-43%, -4%), P=.02) reduced rate of change in CAC; higher paraspinal and oblique muscle area were associated with a 24% (-38%, -6%, P=.01) and a 37% (-53%, -16%, P=.0002) reduced rate of change in CAC, respectively. These associations were not significant in African American or non-Hispanic White women. There were no significant associations of abdominal muscle with CAC presence or extent, nor were there significant ethnicity by muscle interactions in these models.ConclusionsAmong Filipina women, greater abdominal muscle mass is associated with a decreased rate of CAC progression. Higher muscle mass may be important for this group in reducing CVD outcomes.

IntroductionIncreased sedentary behavior predicts greater cardiovascular morbidity and mortality and does so independently of physical activity (PA). This association is only partially explained by body mass index (BMI) and overall body fat, suggesting mechanisms besides general increased adiposity. The purpose of this study was to explore associations of self-reported leisure PA and sitting time with regional fat depositions and abdominal muscle among community-dwelling older adults.MethodsParticipants were 539 diverse adults (mean age = 65 yr) who completed a study visit in 2001-2002. Areas of pericardial, intrathoracic, subcutaneous, visceral, and intermuscular fat, as well as abdominal muscle, were measured using computed tomography. Leisure PA and sitting hours were entered simultaneously into multivariate regression models to determine associations with muscle and fat areas.ResultsAfter adjusting for demographics, smoking, diabetes, hypertension, triglycerides, and cholesterol, greater PA was associated with less intrathoracic, visceral, subcutaneous, and intermuscular fat (for all P < 0.05), while greater sedentary time was associated with greater pericardial and intrathoracic fat (for both P < 0.05). After further adjusting for BMI, each hour of weekly PA was associated with 1.85 cm less visceral fat (P < 0.01) but was not associated with other fat depositions. Conversely, each hour of daily sitting was associated with 2.39 cm more pericardial fat (P < 0.05) but was not associated with any other fat depositions. There were no associations with abdominal muscle area. Adjusting for common inflammatory markers had little effect. Associations between fat and PA were stronger for men.ConclusionsSitting and PA have distinct associations with regional fat deposition in older adults. The association between sitting and pericardial fat could partially explain the link between sitting and coronary heart disease.

BackgroundSerum phosphorus is associated with cardiovascular disease (CVD) in the general population, but may not comprehensively reflect phosphorus homeostasis. Whether urine phosphorus-creatinine ratio (a marker of intestinal absorption) or urine fractional excretion of phosphorus (FEPi; a marker of urinary phosphorus handling) is associated with risk of mortality or CVD is uncertain.Study designProspective observational study.Setting & participants1,325 community-dwelling men 65 years or older participating in the MrOS Study.PredictorSerum phosphorus, urine phosphorus-creatinine ratio, and FEPi.OutcomesAll-cause and CVD death.ResultsMean age was 74 ± 6 (SD) years, estimated glomerular filtration rate was 75 ± 16 mL/min/1.73 m(2), and serum phosphorus level was 3.2 ± 0.4 mg/dL. During a median follow-up of 9.3 years, there were 364 (120 CVD) deaths. After adjustment for demographics, CVD risk factors, and kidney function, the risks of all-cause death in the highest quartiles of serum phosphorus (≥3.6 mg/dL), urine phosphorus-creatinine ratio (≥0.55), and FEPi (≥18%) were 1.63 (95% CI, 1.23-2.17), 1.22 (95% CI, 0.90-1.65), and 0.88 (95% CI, 0.64-1.23), respectively, compared to the lowest quartiles of each. Results were similar for CVD death. Results also were similar in those with estimated glomerular filtration rate ≥60 and