Associations between toxicity-weighted concentrations and dementia risk: Results from the Cardiovascular Health Cognition Study.

BACKGROUND: Air pollution is a modifiable risk factor for dementia. Yet, studies on specific sources of air pollution (i.e., toxic chemical emissions from industrial facilities) and dementia risk are scarce. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults. METHODS: Participants (n = 2770) were ≥ 65 years old (Mean = 75.3, SD = 5.1 years) from the Cardiovascular Health Cognition Study (1992-1999). Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants' baseline census tract, averaged across 1988-1992, and log2-transformed. Dementia status was clinically adjudicated in 1998-1999 and categorized by subtype (Alzheimer's, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with 1) odds of prevalent dementia and 2) incident dementia risk by subtype. RESULTS: After adjusting for individual and census-tract level covariates, a doubling in toxicity-weighted concentrations was associated with 9 % higher odds of prevalent dementia (OR = 1.09, 95 % CI: 1.00, 1.19). In discrete-time survival models, each doubling in toxicity-weighted concentrations was associated with a 16 % greater hazard of vascular dementia (HR = 1.16, 95 % CI: 1.01, 1.34) but was not significantly associated with all-cause, Alzheimer's disease, or mixed dementia (p's > 0.05). DISCUSSION: Living in regions with higher toxicity-weighted concentrations was associated with higher odds of prevalent dementia and a higher risk of incident vascular dementia in this large, community-based cohort of older adults. These findings support the need for additional studies to examine whether toxic chemical emissions from industrial and federal facilities may be a modifiable target for dementia prevention.

Association of Gait Quality With Daily-Life Mobility: An Actigraphy and Global Positioning System Based Analysis in Older Adults.

OBJECTIVE: Walking is a key component of daily-life mobility. We examined associations between laboratory-measured gait quality and daily-life mobility through Actigraphy and Global Positioning System (GPS). We also assessed the relationship between two modalities of daily-life mobility i.e., Actigraphy and GPS. METHODS: In community-dwelling older adults (N = 121, age = 77±5 years, 70% female, 90% white), we obtained gait quality from a 4-m instrumented walkway (gait speed, walk-ratio, variability) and accelerometry during 6-Minute Walk (adaptability, similarity, smoothness, power, and regularity). Physical activity measures of step-count and intensity were captured from an Actigraph. Time out-of-home, vehicular time, activity-space, and circularity were quantified using GPS. Partial Spearman correlations between laboratory gait quality and daily-life mobility were calculated. Linear regression was used to model step-count as a function of gait quality. ANCOVA and Tukey analysis compared GPS measures across activity groups [high, medium, low] based on step-count. Age, BMI, and sex were used as covariates. RESULTS: Greater gait speed, adaptability, smoothness, power, and lower regularity were associated with higher step-counts (0.20<|ρp| < 0.26, p < .05). Age(ß = -0.37), BMI(ß = -0.30), speed(ß = 0.14), adaptability(ß = 0.20), and power(ß = 0.18), explained 41.2% variance in step-count. Gait characteristics were not related to GPS measures. Participants with high (>4800 steps) compared to low activity (steps<3100) spent more time out-of-home (23 vs 15%), more vehicular travel (66 vs 38 minutes), and larger activity-space (5.18 vs 1.88 km2), all p < .05. CONCLUSIONS: Gait quality beyond speed contributes to physical activity. Physical activity and GPS-derived measures capture distinct aspects of daily-life mobility. Wearable-derived measures should be considered in gait and mobility-related interventions.

Cardiorespiratory fitness is associated with hippocampal resting state connectivity in women newly diagnosed with breast cancer.

Background: Breast cancer and its treatment are associated with aberrant patterns of resting state functional connectivity (rsFC) between the hippocampus and several areas of the brain, which may account for poorer cognitive outcomes in patients. Higher cardiorespiratory fitness (CRF) has been associated with enhanced rsFC and cognitive performance; however, these associations have not been well studied in breast cancer. We examined the relationship between CRF, rsFC of the hippocampus, and cognitive performance among women newly diagnosed with breast cancer. Methods: Thirty-four postmenopausal women newly diagnosed with Stage 0-IIIa breast cancer (Mage = 63.59 ± 5.73) were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. During baseline assessments, participants completed functional brain imaging, a submaximal CRF test, and cognitive testing. Whole-brain, seed-based analyses were used to examine the relationship between CRF and hippocampal rsFC, with age, years of education, and framewise displacement included as covariates. Cognition was measured with a battery of validated neurocognitive measures, reduced to seven composite factors. Results: Higher CRF was positively associated with greater rsFC of the hippocampus to a cluster within the dorsomedial and dorsolateral frontal cortex (z-max = 4.37, p = 0.003, cluster extent = 1,020 voxels). Connectivity within cluster peaks was not significantly related to cognitive factors (all ps > 0.05). Discussion: CRF was positively associated with hippocampal rsFC to frontal cortex structures, comprising a network of regions commonly suppressed in breast cancer. Future longitudinal research is needed to explore whether baseline rsFC predicts long-term cognitive resilience in breast cancer.

Peak Expiratory Flow Predicts Incident Dementia in a Representative Sample of U.S. Older Adults: The National Health and Aging Trends Study (NHATS).

BACKGROUND: Dementia is an increasingly important public health problem with various risk factors. Respiratory function, measured via peak expiratory flow (PEF), may be a modifiable dementia risk factor. METHODS: We investigated the association between PEF and incident dementia in 5 935 older adults from the National Health and Aging Trends Study (NHATS) from 2011 to 2014. Baseline PEF, expressed as a standardized residual (SR) percentile, was analyzed as a predictor of incident dementia using discrete-time proportional hazards models, while controlling for several health and sociodemographic covariates. RESULTS: After 14 332 person-years of follow-up, 9.0% (N = 536) had incident cases of dementia. Compared to the lowest PEF category (SR-percentile < 10%), the highest PEF category (SR-percentile ≥ 80%) had 49% lower risk of incident dementia (hazard ratio [HR] = 0.51; 95% confidence interval [CI; 0.37, 0.71]), and the second highest PEF category (SR-percentile 50%-80%) had 25% lower risk of incident dementia (HR = 0.75; 95% CI [0.56, 1.00]). A sensitivity analysis using multiple imputation to account for missing PEF measurements yielded similar associations with incident dementia. CONCLUSION: These associations suggest a dose-dependent relationship such that higher PEF categories were more protective against incident dementia. PEF may be considered as an easily administered, low-cost measure of respiratory function and a potentially modifiable dementia risk factor. Improving PEF may reduce dementia risk through vascular mechanisms, such as increased brain oxygenation. Future research should explore potential causal pathways between PEF and dementia.

Obesity, Psychological Distress, and Resting State Connectivity of the Hippocampus and Amygdala Among Women With Early-Stage Breast Cancer.

Objective: Overweight and obesity [body mass index (BMI) ≥ 25 kg/m2] are associated with poorer prognosis among women with breast cancer, and weight gain is common during treatment. Symptoms of depression and anxiety are also highly prevalent in women with breast cancer and may be exacerbated by post-diagnosis weight gain. Altered brain function may underlie psychological distress. Thus, this secondary analysis examined the relationship between BMI, psychological health, and resting state functional connectivity (rsFC) among women with breast cancer. Methods: The sample included 34 post-menopausal women newly diagnosed with Stage 0-IIa breast cancer (Mage = 63.59 ± 5.73) who were enrolled in a 6-month randomized controlled trial of aerobic exercise vs. usual care. At baseline prior to randomization, whole-brain analyses were conducted to evaluate the relationship between BMI and seed-to-voxel rsFC of the hippocampus and amygdala. Connectivity values from significant clusters were then extracted and examined as predictors of self-reported depression and anxiety. Results: Mean BMI was in the obese range (M = 31.83 ± 6.62). For both seeds examined, higher BMI was associated with lower rsFC with regions of prefrontal cortex (PFC), including ventrolateral PFC (vlPFC), dorsolateral PFC, and superior frontal gyrus (z range = 2.85-4.26). Hippocampal connectivity with the vlPFC was negatively correlated with self-reported anxiety (ß = 0.47, p < 0.01). Conclusion: Higher BMI was associated with lower hippocampal and amygdala connectivity to regions of PFC implicated in cognitive control and emotion regulation. BMI-related differences in hippocampal and amygdala connectivity following a recent breast cancer diagnosis may relate to future worsening of psychological functioning during treatment and remission. Additional longitudinal research exploring this hypothesis is warranted.

Estimating the financial costs associated with a phase III, multi-site exercise intervention trial: Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE).

INTRODUCTION: Supervised exercise interventions are expensive and time intensive. However, there are financial costs to consider in addition to the intervention itself, namely: advertising and recruitment, outcome assessments, and other trial-related costs. OBJECTIVES: In this analysis, we examine the financial costs associated with the administration of Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) to quantify the costs associated with large exercise intervention trials and to provide future investigators with financial estimates if they wish to pursue studies of a similar design. METHODS: Cost per randomized participant were calculated in four areas: (1) advertising and recruitment, (2) outcome assessments, (3) delivery of the intervention, and (4) other trial-related expenses. Overall trial costs associated with data analysis, faculty salaries, and indirect costs were estimated as well. RESULTS: The total cost per randomized participant was estimated to be $16,494. Outcome assessments accounted for the highest proportion of per-participant (75%) and total trial (38%) costs. Neuroimaging assessments (MRI & PET) cost $8247 per randomized participant, accounting for two-thirds (67%) of outcome assessment costs and half (50%) of per-participant costs. CONCLUSION: Large clinical trials of exercise are expensive (~$21 million), particularly when administering several visits to assess study aims. Outcome assessments, specifically those involving neuroimaging, accounted for a significant proportion of total costs in this analysis. Future investigators must budget accordingly if they wish to conduct a comprehensive, multi-site exercise intervention trial that examines numerous physiological and psychological outcomes.

Weight-Loss Outcomes from a Pilot Study of African Dance in Older African Americans.

OBJECTIVE: Obesity is a risk factor for both cognitive and physical impairment in late adulthood. Though the rates of obesity are high in many groups, older African Americans are disproportionately affected. A randomized pilot intervention of African Dance was conducted with 28 African American older adults with obesity (mean age = 68.4 ± 5.1 years; mean BMI = 33.4 ± 6.2). The goal of the study was to evaluate the physiological outcomes of a culturally sensitive exercise intervention and specifically changes in weight. METHODS: Participants were randomly assigned to an African Dance (experimental) or Culture Education (control) group. They attended their assigned class for 1 hour per session, 3 days per week, for 6 months. RESULTS: There was a significant group × time interaction on weight (P  = 0.005) such that the African Dance group lost weight (mean = 4.0 ± 6.0 lb) while the Culture Education group gained weight (mean = 2.6 ± 3.9 lb). CONCLUSIONS: These results suggest that a culturally sensitive form of physical activity, African Dance, may be effective for promoting weight loss in a population at increased risk for obesity and cognitive decline.

Protocol for Exercise Program in Cancer and Cognition (EPICC): A randomized controlled trial of the effects of aerobic exercise on cognitive function in postmenopausal women with breast cancer receiving aromatase inhibitor therapy.

The Exercise Program in Cancer and Cognition (EPICC) Study is a randomized controlled trial designed to test the effects of moderate-intensity aerobic exercise on cognitive function in postmenopausal women with early-stage breast cancer during the first six months of aromatase inhibitor therapy. It is estimated that up to 75% of survivors of breast cancer experience cognitive impairment related to disease and treatment. At present, there are no known interventions to improve or manage cognitive function for women with breast cancer. Here, we describe a single-blinded, randomized controlled trial with allocation of 254 postmenopausal women with early-stage breast cancer to a supervised six-month aerobic exercise intervention or usual care. Prior to beginning aromatase inhibitor (AI) therapy, participants complete baseline assessments of cognitive function, cardiorespiratory fitness, blood-based biomarkers, physical activity and sleep, and symptoms (fatigue, sleep problems, depressive symptoms, anxiety). A random subset of participants (n = 150) undergoes neuroimaging procedures that include structural and functional magnetic resonance imaging assessments. All participants maintain an activity diary; physical activity and sleep monitoring is repeated three and seven months post-randomization. The remaining baseline assessments are repeated seven months post-randomization. If successful, exercise could be a low-cost method to improve cognitive function in women with breast cancer that is easily adaptable to the home or community. TRIAL REGISTRATION: Clinicaltrials.govNCT02793921. Registered 20 May 2016.