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In the past 20 years, white matter (WM) microstructure has been studied predominantly using diffusion tensor imaging (DTI). Decreases in fractional anisotropy (FA) and increases in mean (MD) and radial diffusivity (RD) have been consistently reported in healthy aging and neurodegenerative diseases. To date, DTI parameters have been studied individually (e.g., only FA) and separately (i.e., without using the joint information across them). This approach gives limited insights into WM pathology, increases the number of multiple comparisons, and yields inconsistent correlations with cognition. To take full advantage of the information in a DTI dataset, we present the first application of symmetric fusion to study healthy aging WM. This data-driven approach allows simultaneous examination of age differences in all four DTI parameters. We used multiset canonical correlation analysis with joint independent component analysis (mCCA + jICA) in cognitively healthy adults (age 20–33, n = 51 and age 60–79, n = 170). Four-way mCCA + jICA yielded one high-stability modality-shared component with co-variant patterns of age differences in RD and AD in the corpus callosum, internal capsule, and prefrontal WM. The mixing coefficients (or loading parameters) showed correlations with processing speed and fluid abilities that were not detected by unimodal analyses. In sum, mCCA + jICA allows data-driven identification of cognitively relevant multimodal components within the WM. The presented method should be further extended to clinical samples and other MR techniques (e.g., myelin water imaging) to test the potential of mCCA+jICA to discriminate between different WM disease etiologies and improve the diagnostic classification of WM diseases.

Abstract Sedentary behaviors are increasing at the cost of millions of dollars spent in health care and productivity losses due to physical inactivity-related deaths worldwide. Understanding the mechanistic predictors of sedentary behaviors will improve future intervention development and precision medicine approaches. It has been posited that humans have an innate attraction towards effort minimization and that inhibitory control is required to overcome this prepotent disposition. Consequently, we hypothesized that individual differences in the functional connectivity of brain regions implicated in inhibitory control and physical effort decision making at the beginning of an exercise intervention in older adults would predict the change in time spent sedentary over the course of that intervention. In 143 healthy, low-active older adults participating in a 6-month aerobic exercise intervention (with three conditions: walking, dance, stretching), we aimed to use baseline neuroimaging (resting state functional connectivity of two a priori defined seed regions), and baseline accelerometer measures of time spent sedentary to predict future pre-post changes in objectively measured time spent sedentary in daily life over the 6-month intervention. Our results demonstrated that functional connectivity between (1) the anterior cingulate cortex and the supplementary motor area and (2) the right anterior insula and the left temporoparietal/temporooccipital junction, predicted changes in time spent sedentary in the walking group. Functional connectivity of these brain regions did not predict changes in time spent sedentary in the dance nor stretch and tone conditions, but baseline time spent sedentary was predictive in these conditions. Our results add important knowledge toward understanding mechanistic associations underlying complex out-of-session sedentary behaviors within a walking intervention setting in older adults.

PurposeIncreasing evidence suggests rural breast cancer survivors (BCS) may experience greater burden in symptoms known to be associated with cancer-associated cognitive decline (CACD). Yet, little is known about CACD in rural BCS. This study (1) examined differences in cognitive function, moderate-to-vigorous physical activity (MVPA), and other CACD correlates and (2) tested the effects of MVPA on cognitive function in rural versus urban BCS.MethodsRural and urban BCS (N = 80), matched on age, education, and time since diagnosis from a larger study, completed cognitive tasks assessing processing speed (Trails-B, Mazes, Task-Switch) and working memory (spatial working memory) and questionnaires assessing subjective memory impairment (SMI), MVPA, and CACD correlates (i.e., sleep quality, fatigue, anxiety/depression). Some participants (n = 62) wore an accelerometer to objectively estimate MVPA. Multiple linear regression and multivariate analysis of covariance were used to test study aims.ResultsRural BCS (n = 40, M = 61.1±8.4 years-old) performed significantly slower on Trails-B (p0.28). Regression models did not reveal a significant interaction between MVPA and cognitive performance (all p>0.1); however, estimated marginal means models indicated that the effect of MVPA on processing speed was evident only among rural BCS (Trails-B, p = 0.04; Mazes, p = 0.03).ConclusionsFindings suggest rural BCS may suffer greater CACD and engage in less MVPA. Additional research is warranted to further examine CACD and more effectively promote MVPA in rural BCS.

BackgroundWhile technology advances have increased the popularity of remote interventions in underserved and rural cancer communities, less is understood about technology access and preferences for home-based physical activity programs in this cancer survivor population.PurposeTo determine access, preferences, and needs, for a home-based physical activity program in rural cancer survivors.MethodsA Qualtrics Research Panel was recruited to survey adults with cancer across the United States. Participants self-reported demographics, cancer characteristics, technology access and usage, and preferences for a home-based physical activity program. The Godin Leisure Time Exercise Questionnaire (GLTEQ) assessed current levels of physical activity. Descriptive statistics included means and standard deviations for continuous variables, and frequencies for categorical variables. Independent samples t-tests explored differences between rural and non-rural participants.ResultsParticipants (N=298; mean age=55.2 ± 16.5) had a history of cancer (mean age at diagnosis=46.5), with the most commonly reported cancer type being breast (25.5%), followed by prostate (16.1%). 74.2% resided in rural hometowns. 95% of participants reported accessing the internet daily. On a scale of 0-100, computer/laptop (M=63.4) and mobile phone (M=54.6) were the most preferred delivery modes for a home-based physical activity intervention, and most participants preferred balance/flexibility (72.2%) and aerobic (53.9%) exercises. Desired intervention elements included a frequency of 2-3 times a week (53.5%) for at least 20 minutes (75.7%). While there were notable rural disparities present (e.g., older age at diagnosis, lower levels of education; ps.08). However, bias due to electronic delivery of the survey should not be discounted.ConclusionThese findings provide insights into the preferred physical activity intervention (e.g., computer delivery, balance/flexibility exercises) in rural cancer survivors, while highlighting the need for personalization. Future efforts should consider these preferences when designing and delivering home-based interventions in this population.

IntroductionThe social and behavioral effects of the COVID-19 pandemic have impacted the health and physiology of most people, including those never diagnosed with COVID-19. While the impact of the pandemic has been felt across the lifespan, its effects on cardiorespiratory fitness (commonly considered a reflection of total body health) of older adults and children may be particularly profound due to social distancing and stay-at-home advisories, as well as the closure of sport facilities and non-essential businesses. The objective of this investigation was to leverage baseline data from two ongoing clinical trials to determine if cardiorespiratory fitness and body mass index were different during COVID-19 relative to before COVID-19 in older adults and children.MethodsHealthy older individuals (N = 593; 65–80 years) and 200 typically developing children (8–10 years) completed a graded maximal exercise test and had their height and weight measured.ResultsResults revealed that older adults and children tested during COVID-19 had significantly lower cardiorespiratory fitness levels than those tested before COVID-19 shutdowns (older adults: 30% lower; children: 53% lower; p's ≤ 0.001). In addition, older adults and children tested during COVID-19 had significantly higher BMI (older adults: 31.34 ± 0.57 kg/m2, p = 0.004; children: 19.27 ± 0.44 kg/m2, p = 0.05) than those tested before COVID-19 shutdowns (older adults: 29.51 ± 0.26 kg/m2, children: 18.13 ± 0.35 kg/m2). However, these differences in BMI did not remain significant when controlling for cardiorespiratory fitness.DiscussionResults from this investigation indicate that the COVID-19 pandemic, and behavior changes taken to reduce potential exposure, may have led to lower cardiorespiratory fitness levels in older adults and children, as well as higher body mass index. These findings provide relevant public health information as lower cardiorespiratory fitness levels and higher body mass indexes recorded during the pandemic could have far-reaching and protracted health consequences. Public health guidance is needed to encourage physical activity to maintain cardiorespiratory fitness and healthy body composition.Clinical trial registrationOlder adults: https://clinicaltrials.gov/ct2/show/NCT02875301, identifier: NCT02875301; Children: https://clinicaltrials.gov/ct2/show/NCT03592238, identifier: NCT03592238.

Abstract Background The aim of this paper is to describe the utility of various recruitment modalities utilized in the Working to Increase Stability through Exercise (WISE) study. WISE is a pragmatic randomized trial that is testing the impact of a 3-year, multicomponent (strength, balance, aerobic) physical activity program led by trained volunteers or delivered via DVD on the rate of serious fall-related injuries among adults 65 and older with a past history of fragility fractures (e.g., vertebral, fall-related). The modified goal was to recruit 1130 participants over 2 years in three regions of Pennsylvania. Methods The at-risk population was identified primarily using letters mailed to patients of three health systems and those over 65 in each region, as well as using provider alerts in the health record, proactive recruitment phone calls, radio advertisements, and presentations at community meetings. Results Over 24 months of recruitment, 209,301 recruitment letters were mailed, resulting in 6818 telephone interviews. The two most productive recruitment methods were letters (72% of randomized participants) and the research registries at the University of Pittsburgh (11%). An average of 211 letters were required to be mailed for each participant enrolled. Of those interviewed, 2854 were ineligible, 2,825 declined to enroll and 1139 were enrolled and randomized. Most participants were female (84.4%), under age 75 (64.2%), and 50% took an osteoporosis medication. Not having a prior fragility fracture was the most common reason for not being eligible (87.5%). The most common reason provided for declining enrollment was not feeling healthy enough to participate (12.6%). Conclusions The WISE study achieved its overall recruitment goal. Bulk mailing was the most productive method for recruiting community-dwelling older adults at risk of serious fall-related injury into this long-term physical activity intervention trial, and electronic registries are important sources and should be considered.

Abstract Background Supervised physical activity interventions improve functional health during cancer survivorship, but remain costly and inaccessible for many. We previously reported on the benefits of a DVD-delivered physical activity program (FlexToBa™) in older adults. This is a secondary analysis of the intervention effects among cancer survivors in the original sample. Methods Low active, older adults who self-reported a history of cancer (N = 46; M time since diagnosis = 10.7 ± 9.4 years) participated in a 6-month, home-based physical activity intervention. Participants were randomized to either the DVD-delivered physical activity program focused on flexibility, toning, and balance (FlexToBa™; n = 22) or an attentional control condition (n = 24). Physical function was assessed by the Short Physical Performance Battery (SPPB) at baseline, end of intervention, and at 12 and 24 months after baseline. Results Repeated measures linear mixed models indicated a significant group*time interaction for the SPPB total score (β = − 1.14, p = 0.048), driven by improved function from baseline to six months in the FlexToBa™ group. The intervention group also had improved balance (β = − 0.56, p = 0.041) compared with controls. Similar trends emerged for the SPPB total score during follow-up; the group*time interaction from 0 to 12 months approached significance (β = − 0.97, p = 0.089) and was significant from 0 to 24 months (β = − 1.84, p = 0.012). No significant interactions emerged for other outcomes (ps > 0.11). Conclusions A DVD-delivered physical activity intervention designed for cancer-free older adults was capable of eliciting and maintaining clinically meaningful functional improvements in a subgroup of cancer survivors, with similar effects to the original full sample. These findings inform the dissemination of evidence-based physical activity programs during survivorship. Trial registration ClinicalTrials.gov NCT01030419 . Registered 11 December 2009

BackgroundPhysical activity (PA) is a promising method to improve cognition among middle-aged and older adults. Latinos are at high risk for cognitive decline and engaging in low levels of PA. Culturally relevant PA interventions for middle-aged and older Latinos are critically needed to reduce risk of cognitive decline. We examined changes in cognitive performance among middle-aged and older Latinos participating in the BAILAMOS™ dance program or a health education group and compared the mediating effects of PA between group assignment and change in cognitive domains.MethodsOur 8-month randomized controlled trial tested BAILAMOS™, a 4-month Latin dance program followed by a 4-month maintenance phase. A total of 333 older Latinos aged 55+ were randomized to either BAILAMOS™, or to a health education control group. Neuropsychological tests were administered, scores were converted to z-scores, and specific domains (i.e., executive function, episodic memory, and working memory) were derived. Self-reported PA was assessed, and we reported categories of total PA, total leisure PA, and moderate-to-vigorous PA as minutes/week. A series of ANCOVAs tested changes in cognitive domains at 4 and 8 months. A mediation analysis tested the mediating effects of each PA category between group assignment and a significant change in cognition score.ResultsThe ANCOVAs found significant improvement in working memory scores among participants in the dance group at month 8 [F(1,328) = 5.79, p = 0.017, d = 0.20], but not in executive functioning [F(2,328) = 0.229, p = 0.80, Cohen’s d = 0.07] or episodic memory [F(2,328) = 0.241, p = 0.78, Cohen’s d = 0.05]. Follow-up mediation models found that total PA mediated the relationship between group assignment and working memory, in favor of the dance group (β = 0.027, 95% CI [0.0000, 0.0705]). Similarly, total leisure PA was found to mediate this relationship [β = 0.035, 95% CI (0.0041, 0.0807)].ConclusionA 4-month Latin dance program followed by a 4-month maintenance phase improved working memory among middle-aged and older Latinos. Improvements in working memory were mediated by participation in leisure PA. Our results support the current literature that leisure time PA influences cognition and highlight the importance of culturally relevant PA modalities for Latinos.Clinical Trial Registration[www.ClinicalTrials.gov], identifier [NCT01988233].

Abstract Background The purpose was to prospectively examine the effects of sedentary behaviors on subjective memory impairment in breast cancer survivors (BCS) and the extent to which sleep disturbances mediated this pathway. Methods BCS (N = 380; Mage = 57.38 ± 9.25 years) completed questionnaires assessing demographics, health history, sitting behaviors, sleep disturbance, subjective memory impairment, and moderate‐to‐vigorous physical activity (MVPA) at baseline and 6‐month follow‐up. A subsample (N = 300) wore an accelerometer to objectively estimate sedentary time and MVPA. Structural equation modeling was used to test direct and indirect effects of self‐reported and objectively estimated sedentary behaviors on memory impairment (through sleep disturbance) across time. Models were adjusted for demographic, clinical, and MVPA covariates. Results At baseline, more total daily sitting (γ = 0.23), occupational sitting (γ = 0.11), television viewing (γ = 0.15), and computer use (γ = 0.22) were associated with greater sleep disturbance, which was associated with greater memory impairment (γ = −0.22). Indirect effects of self‐reported sitting on memory were significant. At follow‐up, increased total daily sitting (γ = 0.08) and computer use (γ = 0.14) predicted increased sleep disturbance, which predicted increased memory impairment (γ = −0.09). The indirect path from increased computer use to memory impairment was significant (β = −0.01). In the accelerometer subsample, greater daily sedentary time at baseline was associated with less sleep disturbance (γ = −0.14) and memory impairment (indirect effect: β = 0.03). Conclusions Findings provide early evidence that sedentary contexts may differentially influence sleep disturbance and memory impairment in BCS. Computer use and television viewing may pose the strongest risks to cognitive health. Disparate findings between objective and subjective sedentary measures warrant further research.

White matter deterioration is associated with cognitive impairment in healthy aging and Alzheimer's disease. It is critical to identify interventions that can slow down white matter deterioration. So far, clinical trials have failed to demonstrate the benefits of aerobic exercise on the adult white matter using diffusion Magnetic Resonance Imaging. Here, we report the effects of a 6-month aerobic walking and dance interventions (clinical trial NCT01472744) on white matter integrity in healthy older adults (n = 180, 60–79 years) measured by changes in the ratio of calibrated T1- to T2-weighted images (T1w/T2w). Specifically, the aerobic walking and social dance interventions resulted in positive changes in the T1w/T2w signal in late-myelinating regions, as compared to widespread decreases in the T1w/T2w signal in the active control. Notably, in the aerobic walking group, positive change in the T1w/T2w signal correlated with improved episodic memory performance. Lastly, intervention-induced increases in cardiorespiratory fitness did not correlate with change in the T1w/T2w signal. Together, our findings suggest that white matter regions that are vulnerable to aging retain some degree of plasticity that can be induced by aerobic exercise training. In addition, we provided evidence that the T1w/T2w signal may be a useful and broadly accessible measure for studying short-term within-person plasticity and deterioration in the adult human white matter.

Engaging in musical activities throughout the lifespan may protect against age-related cognitive decline and modify structural and functional connectivity in the brain. Prior research suggests that musical experience modulates brain regions that integrate different modalities of sensory information, such as the insula. Most of this research has been performed in individuals classified as professional musicians; however, general musical experiences across the lifespan may also confer beneficial effects on brain health in older adults. The current study investigated whether general musical experience, characterized using the Goldsmith Music Sophistication Index (Gold-MSI), was associated with functional connectivity in older adults (age = 65.7 ± 4.4, n = 69). We tested whether Gold-MSI was associated with individual differences in the functional connectivity of three a priori hypothesis-defined seed regions in the insula (i.e., dorsal anterior, ventral anterior, and posterior insula). We found that older adults with more musical experience showed greater functional connectivity between the dorsal anterior insula and the precentral and postcentral gyrus, and between the ventral anterior insula and diverse brain regions, including the insula and prefrontal cortex, and decreased functional connectivity between the ventral anterior insula and thalamus (voxel p < 0.01, cluster FWE p < 0.05). Follow-up correlation analyses showed that the singing ability subscale score was key in driving the association between functional connectivity differences and musical experience. Overall, our findings suggest that musical experience, even among non-professional musicians, is related to functional brain reorganization in older adults.

Abstract Background Many breast cancer survivors (BCS) report deficits in cognitive function. Physical activity (PA) has been associated with better processing speed and memory in healthy adults and thus may be a useful method for improving cognition in BCS. The purpose of this study was to examine the effects of an acute bout of PA on processing speed and spatial working memory in a sample of BCS. Methods Using a repeated measures, crossover design, BCS [N = 27; M age (SD) = 49.11(8.05)] completed two sessions in counterbalanced order: 30 min of moderate-intensity treadmill walking and 30 min of seated rest. Women completed cognitive tasks immediately before and after each session. Results Within-subjects repeated measures analyses of variance revealed a significant time by session effect for processing speed reaction time [F (1,25) = 5.02, p = .03, η2 = 0.17]. This interaction was driven by significantly reduced reaction time (e.g., faster response) post-exercise and no change post-rest. Further between-subjects analyses indicated a significant time by session by moderate to vigorous physical activity (MVPA) split [F (1,25) = 5.23, p = .03, η2 = 0.17], such that women who engaged in ≥45 min of average daily MVPA reduced their reaction time post-exercise (p = .01) and increased RT post-rest (p = .06). Time by session effects for spatial working memory 3-item accuracy and 4-item reaction time trended towards significance, p = 0.08 and p = 0.10, respectively, again driven by better performance post-exercise. Conclusions The moderate effect of acute exercise on domains of memory and processing speed in BCS is encouraging. Cancer-related cognitive impairment remains largely misunderstood; however, the results from the present study offer preliminary evidence for the positive relationship between acute exercise and cognition in BCS. Trial registration ClinicalTrials.gov NCT02592070. Registered 30 October 2015. Retroactively registered.

Full and diverse participant enrollment is critical to the success and generalizability of all large-scale Phase III trials. Recruitment of sufficient participants is among the most significant challenges for many studies. The novel SARS-CoV-2 coronavirus pandemic has further changed and challenged the landscape for clinical trial execution, including screening and randomization. The Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE) study has been designed as the most comprehensive test of aerobic exercise effects on cognition and brain health. Here we assess recruitment into IGNITE prior to the increased infection rates in the United States, and examine new challenges and opportunities for recruitment with a goal of informing the remaining required recruitment as infection containment procedures are lifted. The results may assist the design and implementation of recruitment for future exercise studies, and outline opportunities for study design that are flexible in the face of emerging threats.

ObjectiveTo examine the differential effects of acute exercise duration on domains of executive function and processing speed in patients with breast cancer.MethodsParticipants (N = 48, Mage = 56.02 ± 10.99) completed two sessions in counterbalanced order: moderate-intensity treadmill walking and sitting. Participants were also randomized to one of three duration conditions: 10 (n = 15), 20 (n = 16), or 30 (n = 17) min, reflecting the length of time spent walking and sitting. Immediately before and after each session, women completed a battery of cognitive tasks (e.g., inhibition, cognitive flexibility, spatial working memory, and processing speed).ResultsWithin- and between-subjects repeated-measures analyses of variance revealed time by condition interactions on both processing speed (p = 0.02) and spatial working memory (ps < 0.07), such that women demonstrated improved cognitive functioning regardless of the time spent walking. There were also several moderately sized three-way (e.g., time by condition by duration) interactions driven by declines in cognitive functioning after sitting on cognitive flexibility in the 10 (d = -0.96) and 30-min (d = -0.52) groups and inhibition in the 20-min group (d = 0.75). On the processing speed task, women performed significantly faster after walking compared with after sitting in the 20-min group (d = -0.24).ConclusionsFor select cognitive domains, walking anywhere from 10 to 30 min is associated with significant benefits. Our findings suggest the need for further research into the mechanisms and dose–response relationships between acute exercise and cognition as well as how such acute bouts may be accumulated for larger, lasting cognitive benefits after breast cancer.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT04255225

Our jobs can provide intellectually and socially enriched environments but also be the source of major psychological and physical stressors. As the average full-time worker spends >8 h at work per weekday and remains in the workforce for about 40 years, occupational experiences must be important factors in cognitive and brain aging. Therefore, we studied whether occupational complexity and stress are associated with hippocampal volume and cognitive ability in 99 cognitively normal older adults. We estimated occupational complexity, physical stress, and psychological stress using the Work Design Questionnaire (Morgeson and Humphrey, 2006), Quantitative Workload Inventory and Interpersonal Conflict at Work Scale (Spector and Jex, 1998). We found that physical stress, comprising physical demands and work conditions, was associated with smaller hippocampal volume and poorer memory performance. These associations were independent of age, gender, brain size, socioeconomic factors (education, income, and job title), duration of the job, employment status, leisure physical activity and general stress. This suggests that physical demands at work and leisure physical activity may have largely independent and opposite effects on brain and cognitive health. Our findings highlight the importance of considering midlife occupational experiences, such as work physical stress, in understanding individual trajectories of cognitive and brain aging.

Abstract Background Evidence suggests reallocating daily sedentary time to physical activity or sleep confers important health benefits in cancer survivors. Despite emerging research suggesting physical activity as a treatment for cancer-related cognitive impairment (CRCI), little is known about the interactive effects of behaviors across the 24-h period. The present purpose was to examine the cognitive effects of reallocating sedentary time to light-intensity physical activity, moderate-to-vigorous physical activity (MVPA), or sleep in breast cancer survivors. Methods Breast cancer survivors (N = 271, Mage = 57.81 ± 9.50 years) completed iPad-based questionnaires and cognitive tasks assessing demographics, health history, executive function, and processing speed (Task-Switch, Trail Making). Participants wore an accelerometer for seven consecutive days to measure their sedentary, physical activity, and sleep behaviors. Single effects (each behavior individually) and partition (controlling for other behaviors) models were used to examine associations among behaviors and cognitive performance. Isotemporal substitution models were used to test the cognitive effects of substituting 30 min of sedentary time with 30 min of light-intensity activity, MVPA, and sleep. Results MVPA was associated with faster Task-switch reaction time in the partition models (stay: B = − 35.31, p = 0.02; switch: B = − 48.24, p = 0.004). Replacing 30 min of sedentary time with 30 min of MVPA yielded faster reaction times on Task-Switch stay (B = − 29.37, p = 0.04) and switch (B = − 39.49, p = 0.02) trials. In Trails A single effects models, sedentary behavior was associated with faster completion (B = − 0.97, p = 0.03) and light-intensity activity with slower completion (B = 1.25, p = 0.006). No single effects were observed relative to Trails B completion (all p > 0.05). Only the effect of MVPA was significant in the partition models (Trails A: B = − 3.55, p = 0.03; Trails B: B = − 4.46, p = 0.049). Replacing sedentary time with light-intensity activity was associated with slower Trails A (B = 1.55 p = 0.002) and Trails B (B = 1.69, p = 0.02) completion. Replacing light activity with MVPA yielded faster Trails A (B = − 4.35, p = 0.02) and Trails B (B = − 5.23, p = 0.03) completion. Conclusions Findings support previous research suggesting MVPA may be needed to improve cognitive function in breast cancer survivors. Trails findings underscore the need to dissect sedentary contexts to better understand the impact of daily behavioral patterns on CRCI. Additional research investigating the cognitive impacts of behaviors across the 24-h period is warranted. Trial registration This study is registered with United States ClinicalTrials.gov (NCT02523677; 8/14/2015).

Abstract Background Physical activity (PA) participation and adherence among cancer survivors is low, despite research indicating numerous physical, psychological and emotional health benefits of exercise. Tailoring exercise programs specific to the PA preferences in cancer survivors has merit for increasing PA participation and adherence to accrue these benefits. This systematic review identifies and differentiates PA programming and counseling preferences of adult cancer survivors across various cancer survivor groups. Methods PubMed, SPORTDiscus, Scopus, PsycINFO, EMBASE, Web of Science and CINAHL were electronically searched (inception to Oct 2017) and articles were identified using PRISMA guidelines. Two reviewers independently assessed identified articles to determine eligibility and then individually performed a quality assessment on all final studies. Extracted and analyzed data included participant characteristics, interest in exercise counseling and programming, as well as specific exercise and counseling preferences (e.g. location, timing, intensity). Results Forty-one articles were included in this systematic review. Most studies assessed mixed cancer survivor groups or breast cancer survivors. Most cancer survivors felt able and interested in participating in a PA program, though starting a PA program after or before treatment was preferred. Walking was the strongest PA modality preference, and most cancer survivors preferred moderate intensity PA. Cancer survivors also indicated preferences for home-based PA that could take place in the morning. Slight preferences were found towards physical activity counseling delivered by a fitness expert from a cancer center. Both quantitative and qualitative studies were found to be of moderate to high quality based on the Appraisal Tool for Cross-Sectional Studies (AXIS) and the Consolidated Criteria for Reporting Qualitative Research (COREQ), respectively. Conclusion Cancer survivors have an interest in participating in PA programs with walking as the primary modality. Additionally, morning-based PA programs that can be tapered to home-based programs are desirable. However, there was wide variation in other PA preference variables, suggesting multiple program options would be beneficial. Many cancer survivors felt interested and able to participate in PA, and therefore designing PA programs that are tailored to cancer survivors is integral for optimizing recruitment and adherence, as well as enhancing health outcomes in cancer survivors.

We propose a randomized controlled trial (RCT) examining the feasibility of square-stepping exercise (SSE) delivered as a home-based program for older adults with multiple sclerosis (MS). We will assess feasibility in the four domains of process, resources, management and scientific outcomes. The trial will recruit older adults (aged 60 years and older) with mild-to-moderate MS-related disability who will be randomized into intervention or attention control conditions. Participants will complete assessments before and after completion of the conditions delivered over a 12-week period. Participants in the intervention group will have biweekly meetings with an exercise trainer in the Exercise Neuroscience Research Laboratory and receive verbal and visual instruction on step patterns for the SSE program. Participants will receive a mat for home-based practice of the step patterns, an instruction manual, and a logbook and pedometer for monitoring compliance. Compliance will be further monitored through weekly scheduled Skype calls. This feasibility study will inform future phase II and III RCTs that determine the actual efficacy and effectiveness of a home-based exercise program for older adults with MS. Keywords: Exercise, Feasibility, Home-based, Multiple sclerosis, Older adults

Musical practice, including musical training and musical performance, has been found to benefit cognitive function in older adults. Less is known about the role of musical experiences on brain structure in older adults. The present study examined the role of different types of musical behaviors on brain structure in older adults. We administered the Goldsmiths Musical Sophistication Index, a questionnaire that includes questions about a variety of musical behaviors, including performance on an instrument, musical practice, allocation of time to music, musical listening expertise, and emotional responses to music. We demonstrated that musical training, defined as the extent of musical training, musical practice, and musicianship, was positively and significantly associated with the volume of the inferior frontal cortex and parahippocampus. In addition, musical training was positively associated with volume of the posterior cingulate cortex, insula, and medial orbitofrontal cortex. Together, the present study suggests that musical behaviors relate to a circuit of brain regions involved in executive function, memory, language, and emotion. As gray matter often declines with age, our study has promising implications for the positive role of musical practice on aging brain health.

Recent work suggests that the brain can be conceptualized as a network comprised of groups of sub-networks or modules. The extent of segregation between modules can be quantified with a modularity metric, where networks with high modularity have dense connections within modules and sparser connections between modules. Previous work has shown that higher modularity predicts greater improvements after cognitive training in patients with traumatic brain injury and in healthy older and young adults. It is not known, however, whether modularity can also predict cognitive gains after a physical exercise intervention. Here, we quantified modularity in older adults (N = 128, mean age = 64.74) who underwent one of the following interventions for 6 months (NCT01472744 on ClinicalTrials.gov): (1) aerobic exercise in the form of brisk walking (Walk), (2) aerobic exercise in the form of brisk walking plus nutritional supplement (Walk+), (3) stretching, strengthening and stability (SSS), or (4) dance instruction. After the intervention, the Walk, Walk+ and SSS groups showed gains in cardiorespiratory fitness (CRF), with larger effects in both walking groups compared to the SSS and Dance groups. The Walk, Walk+ and SSS groups also improved in executive function (EF) as measured by reasoning, working memory, and task-switching tests. In the Walk, Walk+, and SSS groups that improved in EF, higher baseline modularity was positively related to EF gains, even after controlling for age, in-scanner motion and baseline EF. No relationship between modularity and EF gains was observed in the Dance group, which did not show training-related gains in CRF or EF control. These results are consistent with previous studies demonstrating that individuals with a more modular brain network organization are more responsive to cognitive training. These findings suggest that the predictive power of modularity may be generalizable across interventions aimed to enhance aspects of cognition and that, especially in low-performing individuals, global network properties can capture individual differences in neuroplasticity.

Introduction: Despite the prevalence of and negative health consequences associated with perceived loneliness in older adults, few studies have examined interactions among behavioral, psychosocial, and neural mechanisms. Research suggests that physical activity and improvements in perceived social support and stress are related to reductions in loneliness. Yet, the influence of brain structure on these changes is unknown. The present study examined whether change in regional brain volume mediated the effects of changes in social support and stress on change in perceived loneliness after an exercise intervention. We also examined the extent to which baseline brain volumes moderated the relationship between changes in social support, stress, and loneliness.Methods: Participants were 247 older adults (65.4 ± 4.6 years-old) enrolled in a 6-month randomized controlled trial comprised of four exercise conditions: Dance (n = 69), Strength/Stretching/Stability (n = 70), Walk (n = 54), and Walk Plus (n = 54). All groups met for 1 h, three times weekly. Participants completed questionnaires assessing perceived social support, stress, and loneliness at baseline and post-intervention. Regional brain volumes (amygdala, prefrontal cortex [PFC], hippocampus) before and after intervention were measured with automatic segmentation of each participant's T1-weighted structural MRI. Data were analyzed in a latent modeling framework.Results: Perceived social support increased (p = 0.003), while stress (p < 0.001), and loneliness (p = 0.001) decreased over the intervention. Increased social support directly (−0.63, p < 0.01) and indirectly, through decreased stress (−0.10, p = 0.02), predicted decreased loneliness. Changes in amygdala, PFC, and hippocampus volumes were unrelated to change in psychosocial variables (all p ≥ 0.44). However, individuals with larger baseline amygdalae experienced greater decreases in loneliness due to greater reductions in stress (0.35, p = 0.02). Further, individuals with larger baseline PFC volumes experienced greater reductions in stress due to greater increases in social support (−0.47, p = 0.02). No group differences in these pathways were observed.Conclusions: The social support environment and resulting reductions in stress, as opposed to exercise mode, may represent important features of exercise programs for improving older adults' perceived loneliness. As amygdala volume has been linked to anxiety, depression and impaired cognitive control processes in the PFC, moderation findings suggest further investigation in this area is warranted.Trial Registration: ClinicalTrials.gov identifier NCT01472744 (https://clinicaltrials.gov/ct2/show/NCT01472744?term=NCT01472744&rank=1).

Increased survival rates among breast cancer patients have drawn significant attention to consequences of both the presence of cancer, and the subsequent treatment-related impact on the brain. The incidence of breast cancer and the effects of treatment often result in alterations in the microstructure of white matter and impaired cognitive functioning. However, physical activity is proving to be a successful modifiable lifestyle factor in many studies that could prove beneficial to breast cancer survivors. This study investigates the link between white matter lesion volume, moderate physical activity, and cognition in breast cancer survivors following treatment compared to non-cancer age-matched controls. Results revealed that brain structure significantly predicted cognitive function via mediation of physical activity in breast cancer survivors. Overall, the study provided preliminary evidence suggesting moderate physical activity may help reduce the treatment related risks associated with breast cancer, including changes to WM integrity and cognitive impairment.

Contamination is commonly overlooked in randomized trials. The present study examined contamination (minutes of aerobic activity outside of exercise sessions) within an active control condition in a 6-month randomized exercise trial for older adults. We hypothesized that outside aerobic activity would be greater in the control condition compared to the intervention conditions. Participants (mean age = 65.06 years, 66.2% female) were randomly assigned to: Dance (n = 50), Walking, (n = 108), or Strength/Stretching/Stability (SSS; n = 48). Dance and Walking represented the experimental conditions and SSS the control condition. Participants attended exercise sessions three times weekly for 24 weeks. Participants recorded their physical activity outside of class on a weekly home log. Group assignment and covariates (age, gender, body mass index, exercise session intensity and enjoyment, and program adherence) were examined as predictors of weekly aerobic activity outside of exercise sessions. Participants who returned zero home logs were removed from the dataset (final N = 195). Out-of-class aerobic activity was lowest in the Walking group. Significant effects of gender, group, enjoyment, and intensity on out-of-class weekly aerobic activity were observed, all p

Decline in cognitive performance in old age is linked to both suboptimal neural processing in grey matter (GM) and reduced integrity of white matter (WM), but the whole-brain structure-function-cognition associations remain poorly understood. Here we apply a novel measure of GM processing-moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD)-to study the associations between GM function during resting state, performance on four main cognitive domains (i.e., fluid intelligence, perceptual speed, episodic memory, vocabulary), and WM microstructural integrity in 91 healthy older adults (aged 60-80 years). We modeled the relations between whole-GM SDBOLD with cognitive performance using multivariate partial least squares analysis. We found that greater SDBOLD was associated with better fluid abilities and memory. Most of regions showing behaviorally relevant SDBOLD (e.g., precuneus and insula) were localized to inter- or intra-network "hubs" that connect and integrate segregated functional domains in the brain. Our results suggest that optimal dynamic range of neural processing in hub regions may support cognitive operations that specifically rely on the most flexible neural processing and complex cross-talk between different brain networks. Finally, we demonstrated that older adults with greater WM integrity in all major WM tracts had also greater SDBOLD and better performance on tests of memory and fluid abilities. We conclude that SDBOLD is a promising functional neural correlate of individual differences in cognition in healthy older adults and is supported by overall WM integrity.

Higher cardiorespiratory fitness (CRF) and physical activity (PA) in old age are associated with greater brain structural and functional integrity, and higher cognitive functioning. However, it is not known how different aspects of lifestyle such as sedentariness, light PA (LI-PA), or moderate-to-vigorous physical activity (MV-PA) relate to neural activity in aging. In addition, it is not known whether the effects of PA on brain function differ or overlap with those of CRF. Here, we objectively measured CRF as oxygen consumption during a maximal exercise test and measured PA with an accelerometer worn for 7 days in 100 healthy but low active older adults (aged 60-80 years). We modeled the relationships between CRF, PA, and brain functional integrity using multivariate partial least squares analysis. As an index of functional brain integrity we used spontaneous moment-to-moment variability in the blood oxygenation level-dependent signal (SDBOLD), known to be associated with better cognitive functioning in aging. We found that older adults who engaged more in LI-PA and MV-PA had greater SDBOLD in brain regions that play a role in integrating segregated functional domains in the brain and benefit from greater CRF or PA, such as precuneus, hippocampus, medial and lateral prefrontal, and temporal cortices. Our results suggest that engaging in higher intensity PA may have protective effects on neural processing in aging. Finally, we demonstrated that older adults with greater overall WM microstructure were those showing more LI-PA and MV-PA and greater SDBOLD. We conclude that SDBOLD is a promising correlate of functional brain health in aging. Future analyses will evaluate whether SDBOLD is modifiable with interventions aimed to increase PA and CRF in older adults.

OBJECTIVES:The overall goal of the study was to identify functional and behavioral differences between individuals with higher tinnitus distress and individuals with lower tinnitus distress. Subsequent exploratory analyses were conducted to investigate the role physical activity may have on the observed results between high and low distress groups. The purpose of the experiment was to identify brain regions to be targeted in future intervention studies for tinnitus. DESIGN:A total of 32 individuals with varying levels of tinnitus severity were recruited from the Urbana-Champaign area. Volunteers were divided into higher tinnitus distress (HD) and lower tinnitus distress (LD) groups. Note that these groups also significantly differed based on physical activity level and were subsequently stratified into higher and lower physical activity level subgroups for exploratory analysis. While in a functional magnetic resonance imaging (fMRI) scanner, subjects listened to affective sounds classified as pleasant, neutral or unpleasant from the International Affective Digital Sounds database. RESULTS:The HD group recruited amygdala and parahippocampus to a greater extent than the LD group when listening to affective sounds. The LD group engaged frontal regions to a greater extent when listening to the affective stimuli compared to the HD group. Both higher physical activity level subgroups recruited more frontal regions, and both lower levels of physical activity subgroups recruited more limbic regions respectively. CONCLUSION:Individuals with lower tinnitus distress may utilize frontal regions to better control their emotional response to affective sounds. Our analysis also suggests physical activity may contribute to lower tinnitus severity and greater engagement of the frontal cortices. We suggest that future intervention studies focus on changes in the function of limbic and frontal regions when evaluating the efficacy of treatment. Additionally, we recommend further investigation concerning the impact of physical activity level on tinnitus distress.

Physical activity (PA) and cardiorespiratory fitness (CRF) are associated with better cognitive function in late life, but the neural correlates for these relationships are unclear. To study these correlates, we examined the association of both PA and CRF with measures of white matter (WM) integrity in 88 healthy low-fit adults (age 60-78). Using accelerometry, we objectively measured sedentary behavior, light PA, and moderate to vigorous PA (MV-PA) over a week. We showed that greater MV-PA was related to lower volume of WM lesions. The association between PA and WM microstructural integrity (measured with diffusion tensor imaging) was region-specific: light PA was related to temporal WM, while sedentary behavior was associated with lower integrity in the parahippocampal WM. Our findings highlight that engaging in PA of various intensity in parallel with avoiding sedentariness are important in maintaining WM health in older age, supporting public health recommendations that emphasize the importance of active lifestyle.

To better understand age differences in brain function and behavior, the current study applied network science to model functional interactions between brain regions. We observed a shift in network topology whereby for older adults subcortical and cerebellar structures overlapping with the Salience network had more connectivity to the rest of the brain, coupled with fragmentation of large-scale cortical networks such as the Default and Fronto-Parietal networks. Additionally, greater integration of the dorsal medial thalamus and red nucleus in the Salience network was associated with greater satisfaction with life for older adults, which is consistent with theoretical predictions of age-related increases in emotion regulation that are thought to help maintain well-being and life satisfaction in late adulthood. In regard to cognitive abilities, greater ventral medial prefrontal cortex coherence with its topological neighbors in the Default Network was associated with faster processing speed. Results suggest that large-scale organizing properties of the brain differ with normal aging, and this perspective may offer novel insight into understanding age-related differences in cognitive function and well-being.

Research has shown that aging is associated with increased systemic inflammation as well as a reduction in the strength of immune responses. However, little evidence exists linking the decrease in cell-mediated immunity in older adults with other health parameters. We sought to examine the relationship between cell-mediated immunity as measured in vivo by the delayed-type hypersensitivity (DTH) response to candida antigen and demographic and physiological variables in older (65-80 y.o.) adults. Candida antigen response was not related to gender or obesity, or to a number of other physiological variables including fitness and body composition. However, positive responders had significantly lower serum C-reactive protein levels (CRP, p4.75 mg•L(-1). Therefore, positive responses to candida antigen in older adults appears to be related to lower levels of systemic inflammation.

The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years, N=179). Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum.

A growing body of literature provides evidence for the prophylactic influence of cardiorespiratory fitness on cognitive decline in older adults. This study examined the association between cardiorespiratory fitness and recruitment of the neural circuits involved in an attentional control task in a group of healthy older adults. Employing a version of the Stroop task, we examined whether higher levels of cardiorespiratory fitness were associated with an increase in activation in cortical regions responsible for imposing attentional control along with an up-regulation of activity in sensory brain regions that process task-relevant representations. Higher fitness levels were associated with better behavioral performance and an increase in the recruitment of prefrontal and parietal cortices in the most challenging condition, thus providing evidence that cardiorespiratory fitness is associated with an increase in the recruitment of the anterior processing regions. There was a top-down modulation of extrastriate visual areas that process both task-relevant and task-irrelevant attributes relative to the baseline. However, fitness was not associated with differential activation in the posterior processing regions, suggesting that fitness enhances attentional function by primarily influencing the neural circuitry of anterior cortical regions. This study provides novel evidence of a differential association of fitness with anterior and posterior brain regions, shedding further light onto the neural changes accompanying cardiorespiratory fitness.

Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (.008