Kumar B. Rajan

Adiposity and Sex Hormones in Postmenopausal Breast Cancer Survivors

PURPOSE Overweight and obese women with breast cancer have poorer survival compared with thinner women. One possible reason is that breast cancer survivors with higher degrees of adiposity have higher concentrations of tumor-promoting hormones. This study examined the association between adiposity and concentrations of estrogens, androgens, and sex hormone-binding globulin (SHBG) in a population-based sample of postmenopausal women with breast cancer. METHODS We studied the associations between body mass index (BMI), body fat mass, and percent body fat, measured by dual-energy x-ray absorptiometry scan, waist circumference, and waist-to-hip circumference ratio, with concentrations of estrone, estradiol, testosterone, SHBG, dehydroepiandrosterone sulfate, free estradiol, and free testosterone in 505 postmenopausal women in western Washington and New Mexico with incident stage 0 to IIIA breast cancer. Blood and adiposity measurements were performed between 4 and 12 months after diagnosis. RESULTS Obese women (BMI > or = 30) had 35% higher concentrations of estrone and 130% higher concentrations of estradiol compared with lighter-weight women (BMI < 22.0; P =.005 and.002, respectively). Similar associations were observed for body fat mass, percent body fat, and waist circumference. Testosterone concentrations also increased with increasing levels of adiposity (P =.0001). Concentrations of free estradiol and free testosterone were two to three times greater in overweight and obese women compared with lighter-weight women (P =.0001). CONCLUSION These data provide information about potential hormonal explanations for the association between adiposity and breast cancer prognosis. These sex hormones may be useful biomarkers for weight loss intervention studies in women with breast cancer.

Demographic characteristics of U.S. Chinese older adults in the Greater Chicago area: Assessing the representativeness of the PINE study

Objective: We aimed to assess the representativeness of the demographic characteristics of the PINE study to the Chinese aging population in the Greater Chicago area. Method: The PINE study is a population-based study of Chinese older adults aged 60 and over in the Greater Chicago area. In preparation of the PINE study, we conducted a random block census study in Chicago. Demographic characteristics of the PINE study were compared with the data drawn from U.S. Census 2010 and random block census study using chi-square tests. Results: The PINE study is representative of the Chinese aging population in the Greater Chicago area. No significant difference was found in key attributes including age, sex, income, education, number of children, and country of origin. Discussion: Our report is critical in understanding the vast socio-demographic diversity of U.S. Chinese older adults. Rigorous studies are needed to explore the heterogeneity among the diverse aging populations.

UDP-glucuronosyltransferase and sulfotransferase polymorphisms, sex hormone concentrations, and tumor receptor status in breast cancer patients

IntroductionUDP-glucuronosyltransferase (UGT) and sulfotransferase (SULT) enzymes are involved in removing sex hormones from circulation. Polymorphic variation in five UGT and SULT genes – UGT1A1 ((TA)6/(TA)7), UGT2B4 (Asp458Glu), UGT2B7 (His268Tyr), UGT2B15 (Asp85Tyr), and SULT1A1 (Arg213His) – may be associated with circulating sex hormone concentrations, or the risk of an estrogen receptor-negative (ER-) or progesterone receptor-negative (PR-) tumor.MethodsLogistic regression analysis was used to estimate the odds ratios of an ER- or PR- tumor associated with polymorphisms in the genes listed above for 163 breast cancer patients from a population-based cohort study of women in western Washington. Adjusted geometric mean estradiol, estrone, and testosterone concentrations were calculated within each UGT and SULT genotype for a subpopulation of postmenopausal breast cancer patients not on hormone therapy 2–3 years after diagnosis (n = 89).ResultsThe variant allele of UGT1A1 was associated with reduced risk of an ER- tumor (P for trend = 0.03), and variants of UGT2B15 and SULT1A1 were associated with non-statistically significant risk reductions. There was some indication that plasma estradiol and testosterone concentrations varied by UGT2B15 and SULT1A1 genotypes; women with the UGT2B15 Asp/Tyr and Tyr/Tyr genotypes had higher concentrations of estradiol than women with the Asp/Asp genotype (P = 0.004). Compared with women with the SULT1A1 Arg/Arg and Arg/His genotypes, women with the His/His genotype had elevated concentrations of testosterone (P = 0.003).ConclusionsThe risk of ER- breast cancer tumors may vary by UGT or SULT genotype. Further, plasma estradiol and testosterone concentrations in breast cancer patients may differ depending on some UGT and SULT genotypes.

Perceived stress and change in cognitive function among adults 65 years and older.

Objective Exposure to acute and chronic stress can affect learning and memory, but most evidence comes from animal studies or clinical observations. Almost no population-based studies have investigated the relation of stress to cognition or changes in cognition over time. We examined whether higher levels of perceived stress were associated with accelerated decline in cognitive function in older blacks and whites from a community-based population sample. Methods Participants included 6207 black and white adults (65.7% black, 63.3% women) from the Chicago Health and Aging Project. Two to five in-home assessments were completed over an average of 6.8 years of follow-up and included sociodemographics, health behaviors, psychosocial measures, cognitive function tests, and health history. Perceived stress was measured by a six-item scale, and a composite measure of four tests of cognition was used to determine cognitive function at each assessment. Results Mixed-effects regression models showed that increasing levels of perceived stress were related to lower initial cognitive scores (B = −0.0379, standard error = 0.0025, p < .001) and a faster rate of cognitive decline (stress × time interaction: B = −0.0015, standard error = 0.0004, p < .001). Results were similar after adjusting for demographic variables, smoking, systolic blood pressure, body mass index, chronic medical conditions, and psychosocial factors and did not vary by race, sex, age, or education. Conclusions Increasing levels of stress are independently associated with accelerated declines in cognitive function in black and white adults 65 years and older.

Disability in Basic and Instrumental Activities of Daily Living is Associated with Faster Rate of Decline in Cognitive Function of Older Adults

BACKGROUND The purpose of this study is to examine whether physical disability is associated with faster rate of decline in cognitive function. METHODS A longitudinal population-based cohort of 6,678 initially nondisabled older adults from a biracial urban community was interviewed at 3-year intervals from 1993 to 2012. Cognitive function was assessed using a standardized global cognitive score, and physical disabilities using activities of daily living (ADL) and instrumental activities of daily living (IADL). RESULTS During the follow-up period, 2,450 of 6,678 participants (37%) developed ADL and 2,069 of 4,287 participants (48%) developed IADL disability. After adjusting for demographic and physiologic confounders, cognitive function declined a mean of 0.048 unit per year before ADL disability and 0.047 unit per year before IADL disability. In comparison, the rate of cognitive decline accelerated further by 0.076 unit per year (156% increase) after ADL disability and 0.054 unit per year (115% increase) after IADL disability. Severity of ADL and IADL disabilities were also associated with faster cognitive decline following disability. CONCLUSIONS In old age, cognitive function declines substantially faster following physical disability even after controlling for demographic and physiologic characteristics of participants.

Association of cognitive function and risk for elder abuse in a community-dwelling population.

Aim: This study aimed to examine the cross-sectional association between cognitive function and elder abuse. Methods: The Chicago Health and Aging Project (CHAP) is a population-based study conducted in a geographically defined community (n = 8,932). We identified 238 CHAP participants who had elder abuse reported to a social services agency. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), the Symbol Digit Modalities Test (perceptual speed), and both immediate and delayed recall of the East Boston Memory Test (episodic memory). An index of global cognitive function scores was derived by averaging the z-scores of all tests. Logistic regression models were used to assess the association of cognitive function domains and risk of elder abuse. Results: After adjusting for confounders, lowest tertiles of global cognition (odd’s ratio, OR 4.18, 95% confidence interval, 95% CI 2.44–7.15), MMSE (OR 2.97, 95% CI 1.93–4.57), episodic memory (OR 2.27, 95% CI 1.49–3.43) and perceptual speed (OR 2.37, 95% CI 1.51–3.73) were associated with increased risk of elder abuse. The lowest levels of global cognitive function were associated with an increased risk of physical abuse (OR 3.56, 95% CI 1.08–11.67), emotional abuse (OR 3.02, 95% CI 1.41–6.44), caregiver neglect (OR 6.24, 95% CI 2.68–14.54), and financial exploitation (OR 3.71, 95% CI 1.88–7.32). Conclusion: Lower levels of global cognitive function, MMSE, episodic memory and perceptual speed are associated with an increased risk of elder abuse.

Cognitive impairment 18 years before clinical diagnosis of Alzheimer disease dementia

Objective: To examine the relation of performance on brief cognitive tests to development of clinically diagnosed Alzheimer disease (AD) dementia over the following 18 years in a sample of African Americans and European Americans. Methods: A composite cognitive test score based on tests of episodic memory, executive function, and global cognition was constructed in a prospective population-based sample of 2,125 participants (55% African American and 61% female) aged 65 years and older residing in 4 Chicago neighborhoods. Time before AD dementia diagnosis was categorized into 6 groups corresponding to data collection periods: 0.1–0.9, 1.0–3.9, 4.0–6.9, 7.0–9.9, 10.0–12.9, and 13.0–17.9 years. Results: Of 2,125 participants without clinical AD dementia, 442 (21%) developed clinical AD dementia over 18 years of follow-up. Lower composite cognitive test scores were associated with the development of AD dementia over the duration of the study. The magnitude of association between composite cognitive test score and development of AD dementia increased from an odds ratio of 3.39 (95% confidence interval 1.72, 6.67; p < 0.001) at 13.0–17.9 years to 9.84 (95% confidence interval 7.41, 13.06; p < 0.001) at 0.1–0.9 years, per SD increment. These associations were consistently larger among European Americans than among African Americans. Performance on individual cognitive tests of episodic memory, executive function, and global cognition also significantly predicted the development of AD dementia, with associations exhibiting a similar trend over 18 years. Conclusions: Our findings suggest that cognitive impairment may manifest in the preclinical phase of AD dementia substantially earlier than previously established.

Temporal course of depressive symptoms during the development of Alzheimer disease

Objective: To characterize change in depressive symptoms before and after the onset of dementia in Alzheimer disease (AD). Method: We used data from the Chicago Health and Aging Project, a longitudinal cohort study of risk factors for AD in a geographically defined population of old people. Two subsets were analyzed. In 357 individuals who developed incident AD during the study, self-report of depressive symptoms (Center for Epidemiologic Studies Depression Scale) was obtained at 3-year intervals for a mean of 8 to 9 years. In 340 individuals who agreed to annual data collection, informant report of depressive symptoms (Hamilton Depression Rating Scale) was obtained for a mean of 3 years after a diagnosis of AD (n = 107), mild cognitive impairment (n = 81), or no cognitive impairment (n = 152). Results: The incident AD group reported a barely perceptible increase in depressive symptoms during 6 to 7 years of observation before the diagnosis (0.04 symptoms per year) and no change during 2 to 3 years of observation after the diagnosis except for a slight decrease in positive affect. In those with annual follow-up, neither AD nor its precursor, mild cognitive impairment, was associated with change in informant report of depressive symptoms during a mean of 3 years of observation. Conclusion: Depressive symptoms show little change during the development and progression of AD to a moderate level of dementia severity.

A Randomized Controlled Trial of Mindfulness-Based Stress Reduction to Prevent Flare-Up in Patients with Inactive Ulcerative Colitis

Background/Aims: The primary therapeutic goals in ulcerative colitis (UC) are to maintain excellent quality of life (QOL) by treating flare-ups when they occur, and preventing flare-ups. Since stress can trigger UC flare-ups, we investigated the efficacy of mindfulness-based stress reduction (MBSR) to reduce flare-ups and improve QOL. Methods: Patients with moderately severe UC, in remission, were randomized to MBSR or time/attention control. Primary outcome was disease status. Secondary outcomes were changes in markers of inflammation and disease activity, markers of stress and psychological assessments. Results: 55 subjects were randomized. Absence of flares, time to flare and severity of flare over 1 year were similar between the two groups. However, post hoc analysis showed that MBSR decreased the proportion of participants with at least one flare-up among those with top tertile urinary cortisol and baseline perceived stress (30 vs. 70%; p < 0.001). MBSR patients who flared demonstrated significantly lower stress at the last visit compared to flared patients in the control group (p = 0.04). Furthermore, MBSR prevented a drop in the Inflammatory Bowel Disease Quality of Life Questionnaire during flare (p < 0.01). Conclusion: MBSR did not affect the rate or severity of flare-ups in UC patients in remission. However, MBSR might be effective for those with high stress reactivity (high perceived stress and urinary cortisol) during remission. MBSR appears to improve QOL in UC patients by minimizing the negative impact of flare-ups on QOL. Further studies are needed to identify a subset of patients for whom MBSR could alter disease course.

Advanced adenoma detection rate is independent of nonadvanced adenoma detection rate.

OBJECTIVES:Adenoma detection rate (ADR) is the accepted rate marker in colonoscopy quality. Advanced adenomas detected at index colonoscopy, while less frequent than nonadvanced adenomas, carry greater risk for future advanced neoplasia during surveillance colonoscopy. This study aimed to determine the effect of the colonoscopist and other factors on advanced ADR and to define the correlation of advanced and nonadvanced ADRs among colonoscopists.METHODS:An observational study of a cohort of patients undergoing first-time colorectal cancer screening colonoscopy was conducted. Patient characteristics and colonoscopic findings were collected. Adenoma, advanced adenoma, and nonadvanced ADRs were calculated. Logistic regression was used to determine variable effects on advanced adenoma detection, and Spearmans rank-order correlation was used to evaluate the relationship between advanced and nonadvanced ADRs.RESULTS:A total of 1,944 patients had first-time screening colonoscopies by 14 colonoscopists. All colonoscopists had adequate (>20%) ADRs. The variability in the colonoscopist ranges of detection was 22.22 to 44.66% for adenomas and 2.00 to 18.18% for advanced adenomas. Logistic regression showed that increasing patient age (odds ratio (OR) 1.16 per 5-year increase, 95% confidence interval (CI) 1.05–1.28, P=0.008) and male gender (OR 2.15, 95% CI 1.51–3.06, P<0.0001) were variables associated with advanced adenoma detection. Colonoscopists were significantly different in detecting advanced adenomas by random effects model (P=0.002), adjusting for patient age, gender, race, year of colonoscopy, gastroenterology fellow participation during colonoscopy, and nonadvanced adenomas. Spearmans rank-order correlation coefficient of −0.42 (95% CI −0.77 to 0.14, P=0.13) was not significant and showed no correlation between advanced and nonadvanced adenoma detection by the group of colonoscopists.CONCLUSIONS:Advanced ADR is variable among colonoscopists with acceptable ADRs. Colonoscopists’ advanced ADRs are independent of their nonadvanced ADRs.