Barriers to Mental Health Treatment in Rural Older Adults.

OBJECTIVES: The purpose of this study was to identify the barriers to seeking mental health treatment experienced by rural older adults. We also examined if barriers differed by age and worry severity. METHODS: Participants were 478 rural older adults responding to a flyer for a psychotherapy intervention study. Interested participants were screened by telephone, and barriers to mental health treatment were assessed. Participants completed a demographic questionnaire and the Penn State Worry Questionnaire-Abbreviated. RESULTS: The most commonly reported barrier to treatment was the personal belief that "I should not need help." Other commonly reported barriers included practical barriers (cost, not knowing where to go, distance), mistrust of mental health providers, not thinking treatment would help, stigma, and not wanting to talk with a stranger about private matters. Multivariable analyses indicated that worry severity and younger age were associated with reporting more barriers. CONCLUSIONS: Multiple barriers interfere with older adults seeking treatment for anxiety and depression. Older age is associated with fewer barriers, suggesting that the oldest old may have found strategies for overcoming these barriers. Young-old adults may benefit from interventions addressing personal beliefs about mental health and alternative methods of service delivery.

Intensive lifestyle intervention reduces urinary incontinence in overweight/obese men with type 2 diabetes: results from the Look AHEAD trial.

PURPOSE: We determined the effect of an intensive lifestyle intervention on the prevalence, incidence and resolution of bothersome nocturia, increased daytime urinary voiding and urinary incontinence in overweight/obese men with type 2 diabetes after 1 year in the Look AHEAD trial. MATERIALS AND METHODS: A subset of male Look AHEAD participants was selected for this secondary data analysis. Overall 1,910 men with an average (mean ± SD) age of 59.9 ± 6.7 years and body mass index of 35.2 ± 5.5 kg/m(2) were randomized to an intensive lifestyle intervention or diabetes support and education group. All participants self-reported information regarding incontinence, nocturia and daytime urinary voiding at entry and 1 year. RESULTS: After 1 year the intensive lifestyle intervention group lost significantly more weight than the diabetes support and education group (9.4% ± 7.0% vs 0.7% ± 4.5%, respectively; p <0.001). The odds of prevalent urinary incontinence at 1 year were reduced by 38% in the intensive lifestyle intervention group compared to the diabetes support and education group. The prevalence of urinary incontinence decreased from 11.3% to 9.0% in the intensive lifestyle intervention group and increased from 9.7% to 11.6% in the diabetes support and education group. The intensive lifestyle intervention group also had increased odds of urinary incontinence resolving (OR 1.93, 95% CI 1.04-3.59, p = 0.04 and 56.0% vs 40.7%, p = 0.03) and trend toward reduced odds of new onset, incident urinary incontinence (OR 0.66, 95% CI 0.42-1.02, p = 0.06) compared with the diabetes support and education arm. In contrast, no differences between intensive lifestyle intervention and diabetes support and education were seen at 1 year for frequency of nocturia or frequency of daytime voiding. CONCLUSIONS: Intensive lifestyle intervention should be considered for the treatment of urinary incontinence in overweight/obese men with type 2 diabetes.

Depressive Symptoms and Longitudinal Changes in Cognition: Women's Health Initiative Study of Cognitive Aging.

Elevated depressive symptoms (DS) are associated with incident mild cognitive impairment and probable dementia in postmenopausal women. We examined the association of elevated DS with domain-specific cognitive changes and the moderating role of cardiovascular risk factor severity and cardiovascular disease (CVD). A total of 2221 elderly women who participated in the Women's Health Initiative Study of Cognitive Aging were separated into those with (N = 204) and without (N = 2017) elevated DS. The DS and multidomain cognitive outcomes were measured annually for an average follow-up of 5.04 years. Women with elevated DS showed baseline multidomain cognitive deficits but longitudinal declines in global cognition only. Persistent DS was related to greater global cognition, verbal knowledge and fluency, and memory declines. Significant DS-CVD interactions were observed cross-sectionally (but not longitudinally) for figural memory and fine motor speed. Future studies should investigate the role of nonvascular mechanisms linking DS and cognitive decline.

Weight loss prevents urinary incontinence in women with type 2 diabetes: results from the Look AHEAD trial.

PURPOSE: We determined the effect of weight loss on the prevalence, incidence and resolution of weekly or more frequent urinary incontinence in overweight/obese women with type 2 diabetes after 1 year of intervention in the Look AHEAD (Action for Health in Diabetes) trial. MATERIALS AND METHODS: Women in this substudy (2,739, mean ± SD age 57.9 ± 6.8 years, body mass index 36.5 ± 6.1 kg/m(2)) were randomized into an intensive lifestyle weight loss intervention or a diabetes support and education control condition. RESULTS: At baseline 27% of participants reported urinary incontinence on a validated questionnaire (no significant difference by intensive lifestyle intervention vs diabetes support and education). After 1 year of intervention the intensive lifestyle intervention group in this substudy lost 7.7 ± 7.0 vs 0.7 ± 5.0 kg in the diabetes support and education group. At 1 year fewer women in the intensive lifestyle intervention group reported urinary incontinence (25.3% vs 28.6% in the diabetes support and education group, p = 0.05). Among participants without urinary incontinence at baseline 10.5% of intensive lifestyle intervention and 14.0% of diabetes support and education participants experienced urinary incontinence after 1 year (p = 0.02). There were no significant group differences in the resolution of urinary incontinence (p >0.17). Each kg of weight lost was associated with a 3% reduction in the odds of urinary incontinence developing (p = 0.01), and weight losses of 5% to 10% reduced these odds by 47% (p = 0.002). CONCLUSIONS: Moderate weight loss reduced the incidence but did not improve the resolution rates of urinary incontinence at 1 year among overweight/obese women with type 2 diabetes. Weight loss interventions should be considered for the prevention of urinary incontinence in overweight/obese women with diabetes.

Depressive symptoms, antidepressant use, and future cognitive health in postmenopausal women: the Women's Health Initiative Memory Study.

BACKGROUND: Antidepressants are commonly prescribed medications in the elderly, but their relationship with incident mild cognitive impairment (MCI) and probable dementia is unknown. METHODS: The study cohort included 6,998 cognitively healthy, postmenopausal women, aged 65-79 years, who were enrolled in a hormone therapy clinical trial and had baseline depressive symptoms and antidepressant use history assessments at enrollment, and at least one postbaseline cognitive measurement. Participants were followed annually and the follow-up averaged 7.5 years for MCI and probable dementia outcomes. A central adjudication committee classified the presence of MCI and probable dementia based on extensive neuropsychiatric examination. RESULTS: Three hundred and eighty-three (5%) women were on antidepressants at baseline. Antidepressant use was associated with a 70% increased risk of MCI, after controlling for potential covariates including the degree of depressive symptom severity. Selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) were both associated with MCI (SSRIs: hazard ratios (HR), 1.78 [95% CI, 1.01-3.13]; TCAs: HR, 1.78 [95% CI, 0.99-3.21]). Depressed users (HR, 2.44 [95% CI, 1.24-4.80]), non-depressed users (HR, 1.79 [95% CI, 1.13-2.85]), and depressed non-users (HR, 1.62 [95% CI, 1.13-2.32]) had increased risk of incident MCI. Similarly, all three groups had increased risk of either MCI or dementia, relative to the control cohort. CONCLUSIONS: Antidepressant use and different levels of depression severity were associated with subsequent cognitive impairment in a large cohort of postmenopausal women. Future research should examine the role of antidepressants in the depression-dementia relationship and determine if antidepressants can prevent incident MCI and dementia in individuals with late-life depression subtypes with different levels of severity.

A multifaceted intervention to improve blood pressure control: The Guideline Adherence for Heart Health (GLAD) study.

BACKGROUND: Although high blood pressure is associated with significant morbidity and mortality, the proportion reaching the goal blood pressures as outlined in the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, Treatment of High Blood Pressure (JNC 7) is low. We conducted a randomized trial in primary care practices of a multifactorial intervention targeted to improve providers' adherence to hypertension guidelines. METHOD: A total of 61 primary care practices in North Carolina were randomized to receive either a multifactorial intervention (guideline dissemination via a continuing medical education session, academic detailing sessions, audit and feedback on preintervention rates of adherence, and automated blood pressure machines) or an attention control of similar magnitude but targeted at a different guideline. Outcomes were determined through review of patient charts conducted by an independent masked quality assurance organization. RESULTS: We found no difference between the 2 groups in any of the adherence measures including no difference in the percentage of patients at goal (intervention 49.2%, control 50.6%), with undiagnosed hypertension (18.1% vs 13.6%), average systolic (126 vs 125.1 mm Hg), or diastolic blood pressure (73.1 vs 73.4 mm Hg). Similarly, there was no difference in provider adherence to treatment recommendations (use of thiazide-type diuretic as first-line therapy: 32% vs 29.5%; use of 2-drug therapy in stage 2 hypertension: 11.3% vs 10.4%). CONCLUSION: An intensive, multifactorial intervention did not improve adherence to national hypertension guidelines among community-based primary care. Efforts should be focused on other types of interventions to improve rates of control of hypertension.

Pilot study of a faith-based physical activity program among sedentary blacks.

INTRODUCTION: Physical activity participation is low among blacks, and strategies are needed to successfully create immediate and sustained behavior change related to physical activity. Churches can play an important role in health promotion efforts among blacks because of their central role in spiritual guidance, communication, social support, and networking. This pilot study evaluated the feasibility and acceptability of implementing a physical activity program for sedentary black adults in churches. METHODS: We used a preintervention/postintervention single-group design to evaluate the effect of a 3-month faith-based physical activity intervention on daily walking and moderate- and vigorous-intensity physical activity among sedentary blacks. Eighty-seven black adults participated in eight group sessions that included discussion of physical activity-related topics, an instructor-led physical activity session, and weekly incentives to promote physical activity. We used a questionnaire to assess moderate and vigorous physical activity in minutes per week at baseline and after 3 months. Walking was assessed weekly in steps per day by using a pedometer. RESULTS: Participants (mean age, 52 yrs; mean body mass index, 35 kg/m(2)) reported 27 +/- 54 and 10 +/- 25 minutes per week in moderate-intensity and vigorous-intensity physical activity, respectively, and walked 4822 +/- 2351 steps per day at baseline. After 12 weeks, moderate- and vigorous-intensity physical activity increased by 67 +/- 78 and 44 +/- 66 minutes per week, respectively (P

A Case of Paraneoplastic Cushing Syndrome Presenting as Hyperglycemic Hyperosmolar Nonketotic Syndrome.

Carcinoid tumors are neuroendocrine tumors that mainly arise in the gastrointestinal tract, lungs, and bronchi. Bronchopulmonary carcinoids have been associated with Cushing syndrome, which results from ectopic adrenocorticotrophic hormone (ACTH) secretion. We report the case of a 65-year-old man, a colonel in the US Air Force, with metastatic bronchopulmonary carcinoid tumors treated on a clinical trial who was hospitalized for complaints of increasing thirst, polydipsia, polyuria, weakness, and visual changes. Decompensated hyperglycemia suggested a diagnosis of hyperglycemic hyperosmolar nonketotic syndrome (HHNS). Additional findings, which included hypokalemia, hypernatremia, hypertension, metabolic alkalosis, moon facies, and striae, raised a red flag for an ectopic ACTH syndrome. Elevated ACTH levels confirmed Cushing syndrome. Treatment with a fluid replacement and insulin drip resulted in immediate symptomatic improvement. Cushing syndrome should be considered in carcinoid patients with physical stigmata such as moon facies and striae. HHNS may be the presenting clinical feature in patients with impaired glucose metabolism.

Global Quality of Life Among WHI Women Aged 80 Years and Older.

BACKGROUND: The number of older adults living to age 80 and older is increasing rapidly, particularly among women. Correlates of quality of life (QOL) in very advanced ages are not known. We examined the association of demographic, social-psychological, lifestyle, and physical health variables with global QOL in a Women's Health Initiative (WHI) cohort of women aged 80 and older. METHODS: 26,299 WHI participants, who had completed a recent psychosocial and medical update, were included in these analyses. Global QOL was assessed by a single item, asking the women to rate their overall QOL on a scale from 0 to 10. Characteristics of the women were examined by the level of their transformed global QOL scores (≤50, 50-70, ≥70), and multiple regression was used to examine which demographic, social-psychological, lifestyle and health variables were independently associated with higher global QOL. RESULTS: Social-psychological and current health variables were more strongly associated with global QOL than a history of selected comorbid conditions. In particular, higher self-rated health and fewer depressive symptoms were the most strongly associated with better global QOL in WHI women ≥80 years. CONCLUSIONS: Interventions to reduce depressive symptoms and improve health may lead to better self-reported health and global QOL among older women. Physical and mental health screenings followed by evidence-based interventions are imperative in geriatric care.

The Relationship of Cardiovascular Disease to Physical Functioning in Women Surviving to Age 80 and Above in the Women's Health Initiative.

BACKGROUND: Cardiovascular disease (CVD) is highly prevalent at ages 80 and above. The association of physical functioning (PF), a key to an optimal aging trajectory, with CVD and specific CVD diagnosis in women who survive to age 80 and above has not been described previously and has important public health significance given our aging population. METHODS: Women's Health Initiative participants aged 80 years or older at the time of self-reporting PF (RAND SF-36) were studied in relationship to CVD diagnosis, whether present at study baseline (1993-1998) or diagnosed during follow-up through 2012. Cross-sectional analyses utilized demographic, medical, lifestyle, and psycho-social questionnaire data from baseline or updated at the time of self-reported PF. RESULTS: Among 27,145 older Women's Health Initiative participants, 22.0% (N = 5,959) had been diagnosed with CVD, specifically: 11.3% (N = 3,071) with coronary heart disease; 4.7% (N = 1,279), stroke; 5.2% (N = 1,397), venous thromboembolism; 2.7% (N = 737), peripheral arterial disease; and 2.7% (N = 725), congestive heart failure. PF scores (mean ± SE) were significantly (p < .0001) higher without CVD (60.0 ± 26.9), compared with any CVD (47.9 ± 27.3), and for each specific CVD diagnosis: coronary heart disease (48.8 ± 27.1); stroke (44.8 ± 27.9); venous thromboembolism (48.9 ± 27.4); peripheral arterial disease (41.9 ± 2.2); and congestive heart failure (38.8 ± 26.1). Regardless of CVD diagnosis, higher PF was associated with: younger age at the time of PF assessment; lower body mass index; higher recreational physical activity; better self-reported general health; fewer hip fractures after age 55; no history of arthritis; and no recent use of non-steroidal anti-inflammatory drugs. CONCLUSIONS: Older women with any CVD, and particularly women with congestive heart failure or peripheral arterial disease, reported significantly lower PF compared to women with no CVD. Regardless of CVD diagnosis, higher PF was strongly associated with a more active lifestyle and lower body mass index, suggesting potential intervention targets for more optimal aging.

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 Women's 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.

Telephone-Delivered Cognitive Behavioral Therapy and Telephone-Delivered Nondirective Supportive Therapy for Rural Older Adults With Generalized Anxiety Disorder: A Randomized Clinical Trial.

IMPORTANCE: Generalized anxiety disorder (GAD) is common in older adults; however, access to treatment may be limited, particularly in rural areas. OBJECTIVE: To examine the effects of telephone-delivered cognitive behavioral therapy (CBT) compared with telephone-delivered nondirective supportive therapy (NST) in rural older adults with GAD. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial in the participants' homes of 141 adults aged 60 years and older with a principal or coprincipal diagnosis of GAD who were recruited between January 27, 2011, and October 22, 2013. INTERVENTIONS: Telephone-delivered CBT consisted of as many as 11 sessions (9 were required) focused on recognition of anxiety symptoms, relaxation, cognitive restructuring, the use of coping statements, problem solving, worry control, behavioral activation, exposure therapy, and relapse prevention, with optional chapters on sleep and pain. Telephone-delivered NST consisted of 10 sessions focused on providing a supportive atmosphere in which participants could share and discuss their feelings and did not provide any direct suggestions for coping. MAIN OUTCOMES AND MEASURES: Primary outcomes included interviewer-rated anxiety severity (Hamilton Anxiety Rating Scale) and self-reported worry severity (Penn State Worry Questionnaire-Abbreviated) measured at baseline, 2 months' follow-up, and 4 months' follow-up. Mood-specific secondary outcomes included self-reported GAD symptoms (GAD Scale 7 Item) measured at baseline and 4 months' follow-up and depressive symptoms (Beck Depression Inventory) measured at baseline, 2 months' follow-up, and 4 months' follow-up. Among the 141 participants, 70 were randomized to receive CBT and 71 to receive NST. RESULTS: At 4 months' follow-up, there was a significantly greater decline in worry severity among participants in the telephone-delivered CBT group (difference in improvement, -4.07; 95% CI, -6.26 to -1.87; P = .004) but no significant differences in general anxiety symptoms (difference in improvement, -1.52; 95% CI, -4.07 to 1.03; P = .24). At 4 months' follow-up, there was a significantly greater decline in GAD symptoms (difference in improvement, -2.36; 95% CI, -4.00 to -0.72; P = .005) and depressive symptoms (difference in improvement, -3.23; 95% CI, -5.97 to -0.50; P = .02) among participants in the telephone-delivered CBT group. CONCLUSIONS AND RELEVANCE: In this trial, telephone-delivered CBT was superior to telephone-delivered NST in reducing worry, GAD symptoms, and depressive symptoms in older adults with GAD. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01259596.

Driving with Mild Cognitive Impairment or Dementia: Cognitive Test Performance and Proxy Report of Daily Life Function in Older Women.

OBJECTIVES: To investigate associations between proxy report of cognitive and functional limitations and cognitive performance and current or former driving status in older women with mild cognitive impairment (MCI) and all-cause dementia. DESIGN: Cross-sectional data analysis of retrospectively identified older women with adjudicated MCI and all-cause dementia in the Women's Health Initiative Memory Study-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO). SETTING: Academic medical center. PARTICIPANTS: Women (mean age ± standard deviation 83.7 ± 3.5) adjudicated with MCI or dementia during Year 1, 2, 3, or 4 of the WHIMS-ECHO follow-up period (N = 385). MEASUREMENTS: The telephone-administered cognitive battery included tests of attention, verbal learning and memory, verbal fluency, executive function, working memory, and global cognitive function plus self-report measures of depressive symptomatology. The Dementia Questionnaire (DQ) was administered to a knowledgeable proxy (family member, friend). RESULTS: Sixty percent of women with MCI and 40% of those with dementia are current drivers. Proxy reports of functional limitations in instrumental activities of daily living (IADLs) are associated with current driving status in women with MCI, whereas performance-based cognitive tests are not. In women with dementia, proxy reports of functional limitations in IADLs and performance-based cognitive tests are associated with current driving status, as expected. CONCLUSION: These findings have clinical implications for the importance of evaluating driving concurrently with other instrumental functional abilities in MCI and dementia. Additional work is needed to determine whether proxy report of cognitive and functional impairments should help guide referrals for driving assessment and rehabilitation or counseling for driving transition.

Folate, vitamin B-6, and vitamin B-12 intake and mild cognitive impairment and probable dementia in the Women's Health Initiative Memory Study.

BACKGROUND: Whether higher B vitamin intake (ie, B-6, B-12, and folate) is protective against cognitive decline in later life remains uncertain. Several prospective, observational studies find higher B vitamin intake to be associated with lower risk of dementia; other studies, including most trials of B vitamin supplementation, have observed no effect on cognition. We examined this question in a large population of older women carefully monitored for development of mild cognitive impairment (MCI) and probable dementia. OBJECTIVE: To determine whether baseline folate, vitamin B-6, and/or vitamin B-12 intake, alone or in combination, are associated with incident MCI/probable dementia among older women. DESIGN: Prospective, longitudinal cohort study. Participants were enrolled between 1993 and 1998, and B vitamin intake was self-reported using a food frequency questionnaire administered at baseline. PARTICIPANTS/SETTING: Postmenopausal women (N=7,030) free of MCI/probable dementia at baseline in the Women's Health Initiative Memory Study. MAIN OUTCOME MEASURES: Over a mean follow-up of 5.0 years, 238 cases of incident MCI and 69 cases of probable dementia were identified through rigorous screening and expert adjudication. STATISTICAL ANALYSES: Cox proportional hazard models adjusting for sociodemographic and lifestyle factors examined the association of B vitamin intake above and below the Recommended Daily Allowance and incident MCI/probable dementia. RESULTS: Folate intake below the Recommended Daily Allowance at study baseline was associated with increased risk of incident MCI/probable dementia (hazard ratio 2.0, 95% CI 1.3 to 2.9), after controlling for multiple confounders. There were no significant associations between vitamins B-6 or B-12 and MCI/probable dementia, nor any evidence of an interaction between these vitamins and folate intake. CONCLUSIONS: Folate intake below the Recommended Daily Allowance may increase risk for MCI/probable dementia in later life. Future research should include long-term trials of folic acid supplementation to examine whether folate may impart a protective effect on cognition in later life.

Weight change in the first 2 months of a lifestyle intervention predicts weight changes 8 years later.

OBJECTIVE: Examine the relationship between 1- and 2-month weight loss (WL) and 8-year WL among participants enrolled in a lifestyle intervention. METHODS: 2,290 Look AHEAD participants (BMI: 35.65 ± 5.93 kg/m(2) ) with type 2 diabetes received an intensive behavioral WL intervention. RESULTS: 1- and 2-month WL were associated with yearly WL through Year 8 (P's < 0.0001). At Month 1, participants losing 2-4% and >4% had 1.62 (95% CI: 1.32, 1.98) and 2.79 (95% CI: 2.21, 3.52) times higher odds of achieving ≥5% WL at Year 4 and 1.28 (95% CI: 1.05,1.58) and 1.77 (95% CI: 1.40, 2.24) times higher odds of achieving ≥5% WL at Year 8, compared to those losing <2% initially. At Month 2, 3-6% WL resulted in greater odds of achieving ≥5% WL at Year 4 (OR = 1.85; CI: 1.48, 2.32), and >6% WL resulted in the greatest odds of achieving ≥5% WL at Year 4 (OR = 3.85; CI: 3.05, 4.88) and Year 8 (OR = 2.28; CI: 1.81, 2.89), compared to those losing <3%. Differences in adherence between WL categories were observed as early as Month 2. CONCLUSIONS: 1- and 2-month WL was associated with 8-year WL. Future studies should examine whether alternative treatment strategies can be employed to improve treatment outcomes among those with low initial WL.

Conjugated equine estrogens and global cognitive function in postmenopausal women: Women's Health Initiative Memory Study.

CONTEXT: The Women's Health Initiative Memory Study (WHIMS) previously reported that estrogen plus progestin therapy does not protect cognition among women aged 65 years or older. The effect of estrogen-alone therapy, also evaluated in WHIMS, on cognition has not been established for this population. OBJECTIVES: To determine whether conjugated equine estrogen (CEE) alters global cognitive function in older women and to compare its effect with CEE plus medroxyprogesterone acetate (CEE plus MPA). DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind, placebo-controlled ancillary study of the Women's Health Initiative (WHI), WHIMS evaluated the effect of CEE on incidence of probable dementia among community-dwelling women aged 65 to 79 years with prior hysterectomy from 39 US academic centers that started in June 1995. Of 3200 eligible women free of probable dementia enrolled in the WHI, 2947 (92.1%) were enrolled in WHIMS. Analyses were conducted on the 2808 women (95.3%) with a baseline and at least 1 follow-up measure of global cognitive function before the trial's termination on February 29, 2004. INTERVENTIONS: Participants received 1 daily tablet containing either 0.625 mg of CEE (n = 1387) or matching placebo (n = 1421). MAIN OUTCOME MEASURE: Global cognitive function measured annually with the Modified Mini-Mental State Examination (3MSE). RESULTS: During a mean follow-up of 5.4 years, mean (SE) 3MSE scores were 0.26 (0.13) units lower than among women assigned to CEE compared with placebo (P =.04). For pooled hormone therapy (CEE combined with CEE plus MPA), the mean (SE) decrease was 0.21 (0.08; P =.006). Removing women with dementia, mild cognitive impairment, or stroke from the analyses lessened these differences. The adverse effect of hormone therapy was more pronounced among women with lower cognitive function at baseline (all P<.01). For women assigned to CEE compared with placebo, the relative risk of having a 10-unit decrease in 3MSE scores (>2 SDs) was estimated to be 1.47 (95% confidence interval, 1.04-2.07). CONCLUSION: For women aged 65 years or older, hormone therapy had an adverse effect on cognition, which was greater among women with lower cognitive function at initiation of treatment.

Change in brain and lesion volumes after CEE therapies: the WHIMS-MRI studies.

OBJECTIVES: To determine whether smaller brain volumes in older women who had completed Women's Health Initiative (WHI)-assigned conjugated equine estrogen-based hormone therapy (HT), reported by WHI Memory Study (WHIMS)-MRI, correspond to a continuing increased rate of atrophy an average of 6.1 to 7.7 years later in WHIMS-MRI2. METHODS: A total of 1,230 WHI participants were contacted: 797 (64.8%) consented, and 729 (59%) were rescanned an average of 4.7 years after the initial MRI scan. Mean annual rates of change in total brain volume, the primary outcome, and rates of change in ischemic lesion volumes, the secondary outcome, were compared between treatment groups using mixed-effect models with adjustment for trial, clinical site, age, intracranial volumes, and time between MRI measures. RESULTS: Total brain volume decreased an average of 3.22 cm(3)/y in the active arm and 3.07 cm(3)/y in the placebo arm (p = 0.53). Total ischemic lesion volumes increased in both arms at a rate of 0.12 cm(3)/y (p = 0.88). CONCLUSIONS: Conjugated equine estrogen-based postmenopausal HT, previously assigned at WHI baseline, did not affect rates of decline in brain volumes or increases in brain lesion volumes during the 4.7 years between the initial and follow-up WHIMS-MRI studies. Smaller frontal lobe volumes were observed as persistent group differences among women assigned to active HT compared with placebo. Women with a history of cardiovascular disease treated with active HT, compared with placebo, had higher rates of accumulation in white matter lesion volume and total brain lesion volume. Further study may elucidate mechanisms that explain these findings.

Evaluation of early weight loss thresholds for identifying nonresponders to an intensive lifestyle intervention.

OBJECTIVE: Weight losses in lifestyle interventions are variable, yet prediction of long-term success is difficult. The utility of using various weight loss thresholds in the first 2 months of treatment for predicting 1-year outcomes was examined. METHODS: Participants included 2327 adults with type 2 diabetes (BMI:35.8 ± 6.0) randomized to the intensive lifestyle intervention (ILI) of the Look AHEAD trial. ILI included weekly behavioral sessions designed to increase physical activity and reduce caloric intake. 1-month, 2-month, and 1-year weight changes were calculated. RESULTS: Participants failing to achieve a ≥2% weight loss at Month 1 were 5.6 (95% CI:4.5, 7.0) times more likely to also not achieve a ≥10% weight loss at Year 1, compared to those losing ≥2% initially. These odds were increased to 11.6 (95% CI:8.6, 15.6) when using a 3% weight loss threshold at Month 2. Only 15.2% and 8.2% of individuals failing to achieve the ≥2% and ≥3% thresholds at Months 1 and 2, respectively, go on to achieve a ≥10% weight loss at Year 1. CONCLUSIONS: Given the association between initial and 1-year weight loss, the first few months of treatment may be an opportune time to identify those who are unsuccessful and utilize rescue efforts. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00017953.