Oleg Zaslavsky

Frailty: A Review of the First Decade of Research

Frailty is an emerging geriatric syndrome that refers to a state of increased vulnerability to adverse events including mortality, morbidity, disability, hospitalization, and nursing home admission. Despite its long conceptual and operational history in research and publications, frailty and mechanisms of frailty development are still poorly understood. In this review, we describe a number of conceptual models-reliability, allostatic load, and complexity-that have been put forward to explain the dynamic nature of frailty. We illustrate a consolidated pathophysiological model of frailty, taking into consideration the large and exponentially growing body of studies regarding predictors, indicators, and outcomes of frailty. The model addresses cellular (e.g., oxidative damage and telomere length) and systemic mechanisms (e.g., endocrinal, inflammatory, coagulatory, and metabolic deficiencies) of frailty, moderating or risk factors (e.g., ethnicity, lifestyle, and comorbidities), and outcomes (morbidity, disability, and cognitive decline). Finally, we identify the weaknesses of traditional epidemiological approaches for studying complex phenomena related to frailty and propose areas for future methodological and physiological inquiry.

Duration of Adulthood Overweight, Obesity, and Cancer Risk in the Women's Health Initiative: A Longitudinal Study from the United States.

Background High body mass index (BMI) has become the leading risk factor of disease burden in high-income countries. While recent studies have suggested that the risk of cancer related to obesity is mediated by time, insights into the dose-response relationship and the cumulative impact of overweight and obesity during the life course on cancer risk remain scarce. To our knowledge, this study is the first to assess the impact of adulthood overweight and obesity duration on the risk of cancer in a large cohort of postmenopausal women. Methods and Findings Participants from the observational study of the Women’s Health Initiative (WHI) with BMI information from at least three occasions during follow-up, free of cancer at baseline, and with complete covariate information were included (n = 73,913). Trajectories of BMI across ages were estimated using a quadratic growth model; overweight duration (BMI ≥ 25 kg/m2), obesity duration (BMI ≥ 30 kg/m2), and weighted cumulative overweight and obese years, which take into account the degree of overweight and obesity over time (a measure similar to pack-years of cigarette smoking), were calculated using predicted BMIs. Cox proportional hazard models were applied to determine the cancer risk associated with overweight and obesity duration. In secondary analyses, the influence of important effect modifiers and confounders, such as smoking status, postmenopausal hormone use, and ethnicity, was assessed. A longer duration of overweight was significantly associated with the incidence of all obesity-related cancers (hazard ratio [HR] per 10-y increment: 1.07, 95% CI 1.06–1.09). For postmenopausal breast and endometrial cancer, every 10-y increase in adulthood overweight duration was associated with a 5% and 17% increase in risk, respectively. On adjusting for intensity of overweight, these figures rose to 8% and 37%, respectively. Risks of postmenopausal breast and endometrial cancer related to overweight duration were much more pronounced in women who never used postmenopausal hormones. This study has limitations because some of the anthropometric information was obtained from retrospective self-reports. Furthermore, data from longitudinal studies with long-term follow-up and repeated anthropometric measures are typically subject to missing data at various time points, which was also the case in this study. Yet, this limitation was partially overcome by using growth curve models, which enabled us to impute data at missing time points for each participant. Conclusions In summary, this study showed that a longer duration of overweight and obesity is associated with an increased risk of developing several forms of cancer. Furthermore, the degree of overweight experienced during adulthood seemed to play an important role in the risk of developing cancer, especially for endometrial cancer. Although the observational nature of our study precludes inferring causality or making clinical recommendations, our findings suggest that reducing overweight duration in adulthood could reduce cancer risk and that obesity prevention is important from early onset. If this is true, health care teams should recognize the potential of obesity management in cancer prevention and that excess body weight in women is important to manage regardless of the age of the patient.

Toward a Positive Aging Phenotype for Older Women: Observations From the Women’s Health Initiative

BACKGROUND To develop a positive aging phenotype, we undertook analyses to describe multiple dimensions of positive aging and their relationships to one another in women 65 years of age and older and evaluate the performance of individual indicators and composite factors of this phenotype as predictors of time to death, years of healthy living, and years of independent living. METHODS Data from Womens Health Initiative clinical trial and observational study participants ages 65 years and older at baseline, including follow-up observations up to 8 years later, were analyzed using descriptive statistics and principal components analysis to identify the factor structure of a positive aging phenotype. The factors were used to predict time to death, years of healthy living (without hospitalization or diagnosis of a serious health condition), and years of independent living (without nursing home admission or use of special services). RESULTS We identified a multidimensional phenotype of positive aging that included two factors: Physical-Social Functioning and Emotional Functioning. Both factors were predictive of each of the outcomes, but Physical-Social Functioning was the strongest predictor. Each standard deviation of increase in Physical-Social Functioning was accompanied by a 23.7% reduction in mortality risk, a 19.4% reduction in risk of major health conditions or hospitalizations, and a 26.3% reduction in risk of dependent living. CONCLUSIONS Physical-Social Functioning and Emotional Functioning constitute important components of a positive aging phenotype. Physical-Social Functioning was the strongest predictor of outcomes related to positive aging, including years of healthy living, years of independent living, and time to mortality.

Coffee and caffeine consumption and the risk of hypertension in postmenopausal women

BACKGROUND The associations of coffee and caffeine intakes with the risk of incident hypertension remain controversial. OBJECTIVE We sought to assess longitudinal relations of caffeinated coffee, decaffeinated coffee, and total caffeine intakes with mean blood pressure and incident hypertension in postmenopausal women in the Womens Health Initiative Observational Study. DESIGN In a large prospective study, type and amount of coffee and total caffeine intakes were assessed by using self-reported questionnaires. Hypertension status was ascertained by using measured blood pressure and self-reported drug-treated hypertension. The mean intakes of caffeinated coffee, decaffeinated coffee, and caffeine were 2-3 cups/d, 1 cup/d, and 196 mg/d, respectively. Using multivariable linear regression, we examined the associations of baseline intakes of caffeinated coffee, decaffeinated coffee, and caffeine with measured systolic and diastolic blood pressures at annual visit 3 in 29,985 postmenopausal women who were not hypertensive at baseline. We used Cox proportional hazards models to estimate HRs and their 95% CIs for time to incident hypertension. RESULTS During 112,935 person-years of follow-up, 5566 cases of incident hypertension were reported. Neither caffeinated coffee nor caffeine intake was associated with mean systolic or diastolic blood pressure, but decaffeinated coffee intake was associated with a small but clinically irrelevant decrease in mean diastolic blood pressure. Decaffeinated coffee intake was not associated with mean systolic blood pressure. Intakes of caffeinated coffee, decaffeinated coffee, and caffeine were not associated with the risk of incident hypertension (P-trend > 0.05 for all). CONCLUSION In summary, these findings suggest that caffeinated coffee, decaffeinated coffee, and caffeine are not risk factors for hypertension in postmenopausal women.

Predictors of Optimal Cognitive Aging in 80+ Women: The Women’s Health Initiative Memory Study

BACKGROUND Independent predictors of preserved cognitive functioning and factors associated with maintaining high preserved cognitive function in women ≥ 80 years remain elusive. METHODS Two thousand two hundred twenty-eight women with a mean age of 85 years who participated in the Womens Health Initiative Memory Study were classified as cognitively normal (n = 1,905, 85.5%), mild cognitive impairment (n = 88, 3.9%), dementia (n = 121, 5.4%) or other cognitive impairment (n = 114, n = 5.1%) by central adjudication. Global cognitive functioning was assessed using telephone interview for cognitive status-modified in those women who did not meet cognitive impairment criteria. Differences between women grouped by cognitive status with respect to each potential risk factor were assessed using chi-squared tests and t-tests. Backward stepwise logistic regression was used to select factors that were independently associated with cognitive status. RESULTS Factors associated with preserved cognitive functioning were younger age, higher education, and family incomes, being non-Hispanic white, better emotional wellbeing, fewer depressive symptoms, more insomnia complaints, being free of diabetes, and not carrying the apolipoprotein E-epsilon 4 allele. Cognitively normal women who demonstrated sustained high preserved cognition were younger, more educated, and endorsed better self-reported general health, emotional wellbeing, and higher physical functioning. CONCLUSIONS Addressing sociodemographic disparities such as income inequality, and targeting interventions to improve depressive symptoms and vascular risk factors, including diabetes, may play an important role in preserving cognition among women who survive to 80 years of age. Person-centered approaches that combine interventions to improve physical, cognitive, and psychosocial functioning may promote maintenance of high preserved cognitive health in the oldest-old.

Longitudinal changes in insomnia status and incidence of physical, emotional, or mixed impairment in postmenopausal women participating in the Women's Health Initiative (WHI) study

OBJECTIVES/BACKGROUND We assessed prevalence and correlates of insomnia; associations between changes in insomnia with incidence of physical, emotional, and mixed impairments (PI, EI, and MI, respectively); and age as a moderator in these relationships. PARTICIPANTS/METHODS The Womens Health Initiative (WHI) clinical trial (CT) and observational study (OS) cohorts with 1- and 3-year follow-ups, respectively, were studied. Participants included 39,864 CT and 53,668 OS postmenopausal women free of PI or EI at baseline. Insomnia Rating Scale (IRS), with a cutoff score of ≥9 indicated insomnia. Normal-Normal, Abnormal-Abnormal, Normal-Abnormal, and Abnormal-Normal categories indicated change in insomnia over time. PI, EI, and MI were constructed using Short Form-36 (SF-36) Physical and Emotional subscales (cutoff ≤60) and the modified Center for Epidemiological Studies Depression scale (cutoff ≤0.06). RESULTS Among 93,532 women, 24.5% had insomnia at baseline. The highest odds ratios (ORs) for impairments were found in the Normal-Abnormal and Abnormal-Abnormal categories. In the CT cohort, Normal-Abnormal category, ORs were 1.86 (95% CI = 1.57-2.20) for PI, 4.11 (95% CI = 3.59-4.72) for EI, and 6.37 (95% CI = 4.65-8.74) for MI. Respective ORs for the OS cohort were 1.70 (95% CI = 1.51-1.89), 3.80 (95% CI = 3.39-4.25), and 4.41 (95% CI = 3.56-5.46). Interactions between changes in insomnia and age showed distinct albeit nonsignificant patterns. CONCLUSIONS The results suggest that exposure to insomnia increases vulnerability to impairment. Future studies are needed to understand the directionality of these relationships.

Longitudinal Associations between Self-Rated Health and Performance-Based Physical Function in a Population-Based Cohort of Older Adults

Background Although self-rated health (SRH) and performance-based physical function (PPF) are both strong predictors of mortality, little research has investigated the relationships between them. The objective of this study was to evaluate longitudinal, bi-directional associations between SRH and PPF. Methods We evaluated longitudinal associations between SRH and PPF in 3,610 adults aged 65–89 followed for an average of 4.8 (standard deviation [SD]: 4.4) years between 1994 and July 2011 in the Adult Changes in Thought study, a population-based cohort in the Seattle area. SRH was assessed with a single-item question in the ACT study. Participants were asked at each evaluation to rate their health as “excellent”, “very good”, “good”, “fair”, or “poor” in response to the question “In general, how would you rate your health at this time”. PPF scores (ranging from 0–16, with higher indicating better performance) included walking speed, chair rises, grip strength, and balance. Results At the baseline visit, participants averaged 74.5 (SD: 5.8) years of age and 2,115 (58.6%) were female. In multivariable linear mixed models, PPF declined with age, with more rapid decreases associated with very good, good, and fair (vs. excellent) baseline SRH. Adjusted annual change in PPF was −0.17 points (95% confidence interval [CI]: −0.19, −0.15) for individuals with excellent baseline SRH and −0.21 points (95% CI: −0.22, −0.19) for participants with fair SRH. In multivariable generalized linear mixed models, lower baseline PPF quartiles were associated with lower odds of excellent/very good/good SRH at age 75, however, differences between baseline PPF quartiles diminished with age. Conclusions These results suggest that less than excellent SRH predicts decline in physical functioning, however, poor physical functioning may not predict change in SRH in a reciprocal fashion. SRH provides a simple assessment tool for identifying individuals at increased risk for decline in physical function.

Comparison of frailty phenotypes for prediction of mortality, incident falls, and hip fracture in older women

To compare the ability of the commonly used Womens Health Initiative (WHI) and Cardiovascular Health Study (CHS) frailty phenotypes to predict falls, hip fracture, and death in WHI Clinical Trial participants aged 65 and older.

Impact of Functional Change Before and During Hospitalization on Functional Recovery 1 Month Following Hospitalization

BACKGROUND The functional changes that occur immediately before acute hospitalization and those that occur during hospitalization are pertinent to posthospitalization functional status in older adults. Our primary aim was to estimate the effects of membership in categories that take into account pre- and within-hospital functional changes on the likelihood of functional recovery (FR) 1 month after discharge. METHODS The sample included 691 older (≥70) adults admitted to general-medical inpatient units in two hospitals in Israel. FR was defined as a restoration of functioning 1 month postdischarge to levels reported 2 weeks prior to admission. Patients were classified according to functional decline or stability during the prehospital stage and decline, stability, or improvement between admission and discharge in terms of ability to perform self-care or mobility activities. We performed multivariate logistic regressions to test the association between categories of functional change and FR. RESULTS Patients who remained stable before and during hospitalization had the highest odds of maintaining their premorbid functional levels. Those who experienced functional improvement during hospitalization, despite previous functional loss, were 2.3-2.9 times more likely than persistent decliners to experience FR (p < .05 for all). Comparable patterns were found in the relationship between pre- and in-hospital functional trajectories and recovery, both in self-care and in mobility. CONCLUSIONS Differentiating between pre- and in-hospital functional changes is important for promoting short-term posthospitalization FR. In-hospital function-focused care that takes into account preadmission functional history may help improve posthospitalization FR.

Aging Well Among Women Veterans Compared With Non-Veterans in the Women’s Health Initiative

PURPOSE OF THE STUDY To examine whether Veteran status influences (a) womens survival to age 80 years without disease and disability and (b) indicators of successful, effective, and optimal aging at ages 80 years and older. DESIGN AND METHODS The Womens Health Initiative (WHI) enrolled 161,808 postmenopausal women aged 50-79 years from 1993 to 1998. We compared successful aging indicators collected in 2011-2012 via mailed questionnaire among 33,565 women (921 Veterans) who reached the age of 80 years and older, according to Veteran status. A second analysis focused on women with intact mobility at baseline who could have reached age 80 years by December 2013. Multinominal logistic models examined Veteran status in relation to survival to age 80 years without major disease or mobility disability versus having prevalent or incident disease, having mobility disability, or dying prior to age 80 years. RESULTS Women Veterans aged 80 years and older reported significantly lower perceived health, physical function, life satisfaction, social support, quality of life, and purpose in life scale scores compared with non-Veterans. The largest difference was in physical function scores (53.0 for Veterans vs 59.5 for non-Veterans; p < .001). Women Veterans were significantly more likely to die prior to age 80 years than non-Veteran WHI participants (multivariate adjusted odds ratio = 1.20; 95% confidence interval, 1.04-1.38). In both Veteran and non-Veteran women, healthy survival was associated with not smoking, higher physical activity, healthy body weight, and fewer depressive symptoms. IMPLICATIONS Intervening upon smoking, low physical activity, obesity, and depressive symptoms has potential to improve chances for healthy survival in older women including Veterans.