The relationship between depressive symptoms and subtypes of mild cognitive impairment in post-menopausal women: Results from the Women's Health Initiative Memory Study.

BACKGROUND: Depressive symptoms are associated with age-related cognitive impairment, but the relative risk of specific subtypes of mild cognitive impairment (MCI) conferred by depressive symptoms is unclear. The purpose of this exploratory study was to determine the longitudinal association between baseline depressive symptoms and incident cases of MCI subtypes (amnestic vs. non-amnestic) and probable dementia (PD) (Alzheimer's disease, vascular, mixed) among postmenopausal women. METHODS: Depressive symptoms were assessed at study baseline using an 8-item Burnam algorithm in 7043 postmenopausal women who participated in the Women's Health Initiative Memory Study (WHIMS) and the WHIMS-Epidemiology of Cognitive Health Outcomes (WHIMS-ECHO) extension study. During the median 9.4-year follow-up interval, the presence of MCI and PD was classified by a central adjudication committee. Classification of participants by MCI subtype (amnestic single and multi-domain, non-amnestic single and multi-domain) was done algorithmically based on established criteria using data from annual cognitive testing. RESULTS: At baseline, 557 women (7.9%) had clinically significant depressive symptoms based on Burnam algorithm cut-point of 0.06. Depressive symptoms at baseline were associated with an increased risk of incident amnestic MCI (hazard ratio [HR] = 1.91, 95% confidence interval [CI] 1.32-2.78, p < 0.0001), but not non-amnestic MCI (HR = 1.39, 95% CI 0.91-2.14, p = 0.13) after controlling for demographic factors. This relationship between depressive symptoms and amnestic MCI remained consistent after controlling for lifestyle variables, cardiovascular risk factors, antidepressant use, and history of hormone therapy. There were no significant associations between depressive symptoms and incidence of PD. CONCLUSION: Depressive symptoms at baseline among postmenopausal older women are associated with higher incidence of amnestic MCI, suggesting that they may be an independent risk factor or part of the early prodrome of dementia.

Dementia outcomes after addition of proxy-based assessments for deceased or proxy-dependent participants.

OBJECTIVES: As people age and the incidence of dementia increases, studies of cognitive function continue to be of importance. Ascertaining cognitive data through different mechanisms is necessary to address missing data concerns. METHODS: The Dementia Questionnaire (DQ), which utilizes proxy-based assessments, is a potential tool to determine cognitive status in participants no longer being followed per traditional study protocol. The DQ is currently being used in the Supplemental Case Ascertainment Protocol (SCAP), which is being conducted in an ongoing study of postmenopausal women as part of the Women's Health Initiative Memory Study (WHIMS). RESULTS: Ninety-four percent of the 1260 SCAP participants were eligible because of being deceased. Those who are SCAP eligible were older, were less likely to be a minority, and were more likely to have hypertension, diabetes, and prior history of cardiovascular disease (CVD) as well as being a past or current smoker. SCAP added 109 cases of probable dementia to WHIMS. Risk factor relationships were modified upon inclusion of the SCAP cases including an attenuation of a hormone therapy effect and discovery of a hypertension effect. CONCLUSIONS: Augmenting clinic-based cases with proxy-based assessments is feasible and leads to increased incident cases of dementia. When planning future clinical trials, it may be of study benefit to include a protocol of proxy-based assessments, develop strong relationships with proxies early on in the study, and attempt to maintain this relationship throughout the lifespan of the trial.

Optimal cardiometabolic health and risk of heart failure in type 2 diabetes: an analysis from the Look AHEAD trial.

AIMS: To evaluate the contribution of baseline and longitudinal changes in cardiometabolic health (CMH) towards heart failure (HF) risk among adults with type 2 diabetes (T2D). METHODS AND RESULTS: Participants of the Look AHEAD trial with T2D and without prevalent HF were included. Adjusted Cox models were used to create a CMH score incorporating target levels of parameters weighted based on relative risk for HF. The associations of baseline and changes in the CMH score with risk of overall HF, HF with preserved (HFpEF) and reduced ejection fraction (HFrEF) were assessed using Cox models. Among the 5080 participants, 257 incident HF events occurred over 12.4 years of follow-up. The CMH score included 2 points each for target levels of waist circumference, glomerular filtration rate, urine albumin-to-creatinine ratio, and 1 point each for blood pressure and glycated haemoglobin at target. High baseline CMH score (6-8) was significantly associated with lower overall HF risk (adjusted hazard ratio [HR], ref = low score (0-3): 0.31, 95% confidence interval [CI] 0.21-0.47) with similar associations observed for HFpEF and HFrEF. Improvement in CMH was significantly associated with lower risk of overall HF (adjusted HR per 1-unit increase in score at 4 years: 0.80, 95% CI 0.70-0.91). In the ACCORD validation cohort, the baseline CMH score performed well for predicting HF risk with adequate discrimination (C-index 0.70), calibration (chi-square 5.53, p = 0.70), and risk stratification (adjusted HR [high (6-8) vs. low score (0-3)]: 0.35, 95% CI 0.26-0.46). In the Look AHEAD subgroup with available biomarker data, incorporating N-terminal pro-B-type natriuretic peptide to the baseline CMH score improved model discrimination (C-index 0.79) and risk stratification (adjusted HR [high (8-10) vs. low score (0-4)]: 0.18, 95% CI 0.09-0.35). CONCLUSIONS: Achieving target levels of more CMH parameters at baseline and sustained improvements were associated with lower HF risk in T2D.

Eating pathology and psychological outcomes in young adults in self-regulation interventions using daily self-weighing.

OBJECTIVE: Self-regulation interventions encouraging daily weighing prevent weight gain in young adults; however, concerns have been raised that such interventions may have undesirable effects on eating pathology, depression, and health-related quality of life (HRQL). The present study examined whether self-regulation interventions and self-weighing frequency were associated with these indices in normal weight individuals and those with overweight or obesity. METHODS: Young adults (n = 599), 18-35 years with a body mass index (BMI) 21.0-30.9 kg/m² were randomized to control, self-regulation with small changes (SC) or self-regulation with large changes (LC). Interventions taught frequent self-weighing to guide behavioral changes. SC prescribed daily small decreases in intake and increases in physical activity. LC prescribed a 5- to 10-lb weight loss to buffer against anticipated gains. Psychological indices were assessed at baseline and periodically over 2 years of follow-up. RESULTS: There was no evidence that the interventions increased depressive symptoms or compensatory behaviors or decreased HRQL relative to control. LC increased flexible and rigid control and SC decreased disinhibition. Results did not differ by weight status with the exception of rigid control; here, differences between LC and the other conditions were smaller among those with BMI ≥ 25. Greater self-weighing frequency over time was associated with increases in flexible and rigid control, dietary restraint, and improvements in HRQL. CONCLUSIONS: The self-regulation interventions and increases in self-weighing had no untoward effects. Encouraging weight gain prevention in young adults through frequent weighing and self-regulation appears to be safe for normal weight young adults and those with overweight. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Weight and Shape Concern Impacts Weight Gain Prevention in the SNAP Trial: Implications for Tailoring Intervention Delivery.

OBJECTIVE: The Study of Novel Approaches to Weight Gain Prevention (SNAP) trial demonstrated that two self-regulatory interventions prevented weight gain in young adults. Weight and shape concern (WSC) at baseline was evaluated as a moderator of weight outcomes at 24 months. METHODS: Young adults (n = 599) were randomized to self-regulation with small changes (to create 200 kcal/day deficit), self-regulation with large changes (to facilitate preemptive weight loss of 5-10 lb), or self-guided control. WSC was assessed by using one item from the Eating Disorders Assessment. ANOVA was used to examine whether the association between baseline level of WSC and percent weight change over 24 months differed across treatment conditions. RESULTS: Approximately 22% of participants reported high WSC (37% moderate; 41% low). WSC and treatment condition interacted to influence weight change at 24 months (P = 0.03). Individuals with high WSC gained weight in the large changes group (WSC least squares means ± SE, high: + 0.73% ± 1.19%; moderate: -2.74% ± 0.84%; low: -2.41% ± 0.79%). The small changes condition was particularly effective for those with high WSC (high WSC: -2.49% ± 1.16%; moderate: -0.60% ± 0.88%; low: -0.71% ± 0.80%). WSC did not impact weight change among control participants. CONCLUSIONS: Individuals with high WSC may benefit from a small-changes approach to weight gain prevention. These findings indicate WSC may be used to match individuals to weight gain prevention treatment conditions.

Negative Affect Is Associated With Higher Risk of Incident Cognitive Impairment in Nondepressed Postmenopausal Women.

Background: Positive affect (PA) and negative affect (NA) reflect subjective emotional experiences. Although related to depression and anxiety, these dimensions are distinct constructs representing affective states and patterns. Prior studies suggest that elevated depressive symptoms are associated with risk of mild cognitive impairment (MCI) and probable dementia, but whether affective states are associated with cognitive impairment is still unknown. The present study examined relationships between baseline affective states and cognitive impairment (MCI, probable dementia) in nondepressed women. Method: Baseline PA and NA were assessed in postmenopausal women (N = 2,137; mean age = 73.8 years) from the Women's Health Initiative Study of Cognitive Aging (WHISCA) using the Positive and Negative Affect Schedule (PANAS). Women were followed annually for an average of 11.3 years; those with elevated depressive symptoms at baseline were excluded. Results: Higher NA was associated with a higher risk of MCI and probable dementia, even after adjusting for important covariates including age, education, sociodemographic, lifestyle, and cardiovascular risk factors, global cognition, and hormone therapy assignment at baseline. PA was not significantly associated with either outcome. Conclusions: We present the first evidence to date that greater NA, even in the absence of elevated depressive symptoms, is associated with higher risk of MCI and dementia. This suggests that NA may be an important, measureable and potentially modifiable risk factor for age-related cognitive decline.

Improvements in Cardiovascular Risk Factors in Young Adults in a Randomized Trial of Approaches to Weight Gain Prevention.

OBJECTIVE: Weight gain occurs commonly in young adults and increases the risk of cardiovascular disease (CVD). Following on a previous report that two self-regulation interventions reduced weight gain relative to control, this study examines whether these interventions also benefit CVD risk factors. METHODS: The Study of Novel Approaches to Weight Gain Prevention was a randomized trial in two academic settings (N = 599; 18-35 years; BMI 21-30 kg/m2 ) comparing two interventions (Self-Regulation with Small Changes; Self-Regulation with Large Changes) and a control group. Small Changes taught participants to make daily small changes in calorie intake (approximately 100 calories) and activity. Large Changes taught participants to initially lose 5 to 10 pounds to buffer anticipated weight gains. CVD risk factors were assessed at baseline and at 2 years in 471 participants. RESULTS: Although Large Changes was associated with more beneficial changes in glucose, insulin, and homeostatic model assessment of insulin resistance than Control, these differences were not significant after adjusting for multiple comparisons or 2-year weight change. Comparison of participants grouped by percent weight change from baseline to 2 years showed significant differences for several CVD risk factors, with no interaction with treatment condition. CONCLUSIONS: Magnitude of weight change, rather than specific weight gain prevention interventions, was related to changes in CVD risk factors in young adults.

Baseline blood pressure control in Hispanics: characteristics of Hispanics in the Systolic Blood Pressure Intervention Trial.

The Systolic Blood Pressure Intervention Trial (SPRINT) tested whether a systolic blood pressure (SBP) value <120 mm Hg reduces adverse clinical outcomes compared with the goal of <140 mm Hg. Here the authors describe the baseline characteristics of Hispanic participants in SPRINT. Nondiabetic hypertensive patients 50 years and older with SBP 130-180 mm Hg taking zero to four blood pressure (BP) medications were enrolled from the mainland United States and Puerto Rico. Cross-sectional, bivariate analysis was employed comparing sociodemographic and clinical factors in Hispanics vs non-Hispanics. Multivariable logistic regression models restricted to Hispanics were used to identify factors associated with achieved BP control (SBP <140 mm Hg and diastolic BP <90 mm Hg) at baseline. Eleven percent (n=984) of SPRINT participants were Hispanic; 56% (n=549) of Hispanics were living in Puerto Rico and the remainder were living on the US mainland. Hispanics overall were younger, more often female, less likely to live alone, and more likely to have lower education and be uninsured, although just as likely to be employed compared with non-Hispanics. BP control was not different between Hispanics vs non-Hispanics at baseline. However, a significantly higher percentage of Hispanics on the US mainland (compared with Hispanics in Puerto Rico) had controlled BP. BP control was independently associated with cardiovascular disease history and functional status among Hispanics, specifically those living in Puerto Rico, whereas functional status was the only independent predictor of BP control identified among mainland Hispanics. These findings highlight the diversity of the SPRINT population. It remains to be seen whether factors identified among Hispanics impact intervention goals and subsequent clinical outcomes.

The Effect of Intentional Weight Loss on Fracture Risk in Persons With Diabetes: Results From the Look AHEAD Randomized Clinical Trial.

Intentional weight loss is an important treatment option for overweight persons with type 2 diabetes mellitus (DM), but the effects on long-term fracture risk are not known. The purpose of this Look AHEAD analysis was to evaluate whether long-term intentional weight loss would increase fracture risk in overweight or obese persons with DM. Look AHEAD is a multicenter, randomized clinical trial. Recruitment began in August 2001 and follow-up continued for a median of 11.3 years at 16 academic centers. A total of 5145 persons aged 45 to 76 years with DM were randomized to either an intensive lifestyle intervention (ILI) with reduced calorie consumption and increased physical activity designed to achieve and maintain ≥7% weight loss or to diabetes support and education intervention (DSE). Incident fractures were ascertained every 6 months by self-report and confirmed with central adjudication of medical records. The baseline mean age of participants was 59 years, 60% were women, 63% were white, and the mean BMI was 36 kg/m2 . Weight loss over the intervention period (median 9.6 years) was 6.0% in ILI and 3.5% in DSE. A total of 731 participants had a confirmed incident fracture (358 in DSE versus 373 in ILI). There were no statistically significant differences in incident total or hip fracture rates between the ILI and DSE groups. However, compared to the DSE group, the ILI group had a statistically significant 39% increased risk of a frailty fracture (HR 1.39; 95% CI, 1.02 to 1.89). An intensive lifestyle intervention resulting in long-term weight loss in overweight/obese adults with DM was not associated with an overall increased risk of incident fracture but may be associated with an increased risk of frailty fracture. When intentional weight loss is planned, consideration of bone preservation and fracture prevention is warranted. © 2017 American Society for Bone and Mineral Research.

Innovative Self-Regulation Strategies to Reduce Weight Gain in Young Adults: The Study of Novel Approaches to Weight Gain Prevention (SNAP) Randomized Clinical Trial.

IMPORTANCE: Weight gain occurs commonly in young adults and has adverse effects on health. OBJECTIVE: To compare 2 self-regulation interventions vs control in reducing weight gain in young adults over a mean follow-up of 3 years. DESIGN, SETTING, AND PARTICIPANTS: Randomized clinical trial in 2 academic settings of 599 participants aged 18 to 35 years with body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) of 21.0 to 30.0, recruited via mailings and emails from August 2010 to February 2012. Data were analyzed from January 2015 to January 2016. INTERVENTIONS: Participants were randomized to control, self-regulation plus small changes, or self-regulation plus large changes. Both interventions focused on frequent self-weighing to cue behavior changes. "Small changes" taught participants to reduce intake and increase activity, both by approximately 100 calories per day. "Large changes" focused on losing 2.3 to 4.5 kg initially to buffer against expected weight gain. MAIN OUTCOMES AND MEASURES: Changes in weight from baseline over mean follow-up of 3 years. Secondary outcomes included proportion gaining at least 0.45 kg from baseline, proportion developing obesity (BMI, ≥30.0), and weight change baseline to 2 years. RESULTS: Among the 599 participants (22% men; 27% minority; mean [SD] age, 27.7 [4.4] years; mean [SD] BMI, 25.4 [2.6]), mean (SE) weight changes over a mean follow-up of 3 years were 0.26 (0.22), -0.56 (0.22), and -2.37 (0.22) kg in the control, small-changes, and large-changes groups, respectively (P < .001). Differences among all 3 groups were significant (large changes vs control, P < .001; small changes vs control, P = .02; large changes vs small changes, P < .001). On secondary outcomes, both interventions significantly reduced incidence of obesity relative to control (mean [SE], 8.6% [2.0%], 7.9% [2.0%], and 16.9% [2.7%] in the large-changes, small-changes, and control groups, respectively; P = .02 for large changes vs control and P = .002 for small changes vs control); a smaller percentage of participants in the large-changes group gained 0.45 kg or more (mean [SE], 23.6% [2.8%], 32.5% [3.8%], and 40.8% [4.4%], respectively; P < .001 vs control and P = .02 vs small changes) and weight change from baseline to 2 years was greater in control than in small or large changes (mean [SE], 0.54 [0.33], -0.77 [0.33], and -1.50 [0.34] kg, respectively; P = .02 vs small changes and P < .001 vs large changes). CONCLUSIONS AND RELEVANCE: Self-regulation with large or small changes both reduced weight gain in young adults over 3 years relative to control, but the large-changes intervention was more effective. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01183689.