Effects and Mechanisms of Cognitive, Aerobic Exercise, and Combined Training on Cognition, Health, and Brain Outcomes in Physically Inactive Older Adults: The Projecte Moviment Protocol.

INTRODUCTION: Age-related health, brain, and cognitive impairment is a great challenge in current society. Cognitive training, aerobic exercise and their combination have been shown to benefit health, brain, cognition and psychological status in healthy older adults. Inconsistent results across studies may be related to several variables. We need to better identify cognitive changes, individual variables that may predict the effect of these interventions, and changes in structural and functional brain outcomes as well as physiological molecular correlates that may be mediating these effects. Projecte Moviment is a multi-domain randomized trial examining the effect of these interventions applied 5 days per week for 3 months compared to a passive control group. The aim of this paper is to describe the sample, procedures and planned analyses. METHODS: One hundred and forty healthy physically inactive older adults will be randomly assigned to computerized cognitive training (CCT), aerobic exercise (AE), combined training (COMB), or a control group. The intervention consists of a 3 month home-based program 5 days per week in sessions of 45 min. Data from cognitive, physical, and psychological tests, cardiovascular risk factors, structural and functional brain scans, and blood samples will be obtained before and after the intervention. RESULTS: Effects of the interventions on cognitive outcomes will be described in intention-to-treat and per protocol analyses. We will also analyze potential genetic, demographic, brain, and physiological molecular correlates that may predict the effects of intervention, as well as the association between cognitive effects and changes in these variables using the per protocol sample. DISCUSSION: Projecte Moviment is a multi-domain intervention trial based on prior evidence that aims to understand the effects of CCT, AE, and COMB on cognitive and psychological outcomes compared to a passive control group, and to determine related biological correlates and predictors of the intervention effects.Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT03123900.

Investigating Gains in Neurocognition in an Intervention Trial of Exercise (IGNITE): Protocol.

Despite the ubiquity of normal age-related cognitive decline there is an absence of effective approaches for improving neurocognitive health. Fortunately, moderate intensity exercise is a promising method for improving brain and cognitive health in late life, but its effectiveness remains a matter of skepticism and debate because of the absence of large, comprehensive, Phase III clinical trials. Here we describe the protocol for such a randomized clinical trial called IGNITE (Investigating Gains in Neurocognition in an Intervention Trial of Exercise), a study capable of more definitively addressing whether exercise influences cognitive and brain health in cognitively normal older adults. We are conducting a 12-month, multi-site, randomized dose-response exercise trial in 639 cognitively normal adults between 65 and 80 years of age. Participants are randomized to (1) a moderate intensity aerobic exercise condition of 150 min/week (N = 213), (2) a moderate intensity aerobic exercise condition at 225 min/week (N = 213), or (3) a light intensity stretching-and-toning control condition for 150 min/week (N = 213). Participants are engaging in 3 days/week of supervised exercise and two more days per week of unsupervised exercise for 12 months. A comprehensive cognitive battery, blood biomarkers and battery of psychosocial questionnaires is assessed at baseline, 6 and 12-months. In addition, brain magnetic resonance imaging, physiological biomarkers, cardiorespiratory fitness, physical function, and positron emission tomography of amyloid deposition are assessed at baseline and at the 12-month follow-up. The results from this trial could transform scientific-based policy and health care recommendations for approaches to improve cognitive function in cognitively normal older adults.

Associations between cardiorespiratory fitness, physical activity, intraindividual variability in behavior, and cingulate cortex in younger adults.

BACKGROUND: Higher levels of cardiorespiratory fitness (CRF) and greater amounts of physical activity have been associated with lower intraindividual variability (IIV) in executive function in children and older adults. In the present study, we examined whether CRF, measured as maximal oxygen uptake (VO2max), and daily volume of moderate-to-vigorous intensity physical activity (MVPA) were associated with IIV of reaction time during performance of the incongruent condition of the Stroop task in younger adults. Further, we examined whether the thickness of the cingulate cortex was associated with regulating variability in reaction time performance in the context of CRF or physical activity. METHODS: CRF (measured as VO2max), accelerometry-measured MVPA, Stroop performance, and thickness of the rostral anterior cingulate cortex (rACC) derived from magnetic resonance imaging data were collected in 48 younger adults (age = 24.58 ± 4.95 years, mean ± SD). Multiple regression was used to test associations between IIV during the Stroop task and CRF, MVPA, and rACC thickness. Mediation was tested using maximum likelihood estimation with bootstrapping. RESULTS: Consistent with our predictions, higher VO2max was associated with greater rACC thickness for the right hemisphere and greater daily amounts of MVPA were associated with greater rACC thickness for both the left and right hemispheres. Greater thickness of the right rACC was associated with lower IIV for the incongruent condition of the Stroop task. CRF and MVPA were not directly associated with IIV. However, we did find that IIV and both CRF and MVPA were indirectly associated via the thickness of the right rACC. CONCLUSION: These results indicate that higher CRF and greater daily volume of MVPA may be associated with lower IIV during the Stroop task via structural integrity of the rACC. Randomized controlled trials of MVPA would provide crucial information about the causal relations between these variables.

Higher Cardiorespiratory Fitness is Associated with Reduced Functional Brain Connectivity During Performance of the Stroop Task.

BACKGROUND: Although higher cardiorespiratory fitness (CRF) has been linked to better executive function, the mechanisms by which this occurs remain a matter of speculation. One hypothesis is that higher CRF is associated with elevated top-down control in which brain regions processing task-relevant information are up-regulated and brain regions processing task-irrelevant information are down-regulated. METHODS: We tested this top-down hypothesis in 50 young adults (µ age = 25.22 ±â€Š5.17 years) by measuring CRF via a graded maximal exercise test and performing functional Magnetic Resonance Imaging (fMRI) during a color-word Stroop task. We used task-evoked functional connectivity, quantified from a psychophysiological interaction analysis (PPI), to test our hypotheses that (a) higher CRF would be associated with greater connectivity between control centers (i.e., prefrontal and parietal areas) and visual feature centers (i.e., occipital areas) that are involved with processing task-relevant stimulus dimensions (i.e., color), and (b) higher CRF would be associated with lower connectivity between control centers and visual feature centers that are involved with processing task-irrelevant dimensions of the stimuli (i.e., word processing areas). RESULTS: Controlling for sex and BMI, we found, consistent with our second hypothesis, that higher CRF was associated with reduced functional connectivity between parietal and occipital areas involved in the task-irrelevant dimension of the task (i.e., word form areas). There were no associations between CRF and functional connectivity with the prefrontal cortex or evidence of heightened connectivity between attentional control and visual feature centers. CONCLUSIONS: These results suggest that CRF associations with executive functioning might be explained by CRF-mediated differences between brain regions involved with attentional control (parietal regions) and the down-regulation of regions involved with processing task-irrelevant stimulus features (occipital regions).

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.

Cardiorespiratory fitness is associated with enhanced hippocampal functional connectivity in healthy young adults.

Consistent associations have been found between higher cardiorespiratory fitness (CRF) and indices of enhanced brain health and function, including behavioral measures of cognition as well as neuroimaging indicators such as regional brain volume. Several studies have reported that higher CRF levels are associated with a larger hippocampus, yet associations between volume and memory or functional connectivity metrics remain poorly understood. Using a multi-modal framework, we hierarchically examine the association between CRF and hippocampal volume and resting state functional connectivity (rsFC) in younger adults, as well as their relationship between with memory function. We conducted theoretically-driven analyses with seeds in the anterior and posterior hippocampus, as well as control seeds in the caudate nucleus. We tested whether (1) hippocampal connectivity with prefrontal cortical regions was associated with CRF in an adult sample much younger than traditionally tested, (2) associations between CRF and rsFC remain significant after adjusting for volume, and (3) volume and rsFC are related to memory. We found that higher CRF levels were associated with larger anterior hippocampal volume and more positive rsFC of the anterior hippocampus to several regions including the prefrontal cortex. rsFC also accounted for significant variance in CRF, above and beyond volume. CRF can thus be independently linked to increased anterior hippocampal volume, as well as stronger hippocampal rsFC in a population much younger than those typically tested, suggesitng it is critical to maintainig multiple aspects of brain health.

Physical Activity Is Associated with Reduced Implicit Learning but Enhanced Relational Memory and Executive Functioning in Young Adults.

Accumulating evidence suggests that physical activity improves explicit memory and executive cognitive functioning at the extreme ends of the lifespan (i.e., in older adults and children). However, it is unknown whether these associations hold for younger adults who are considered to be in their cognitive prime, or for implicit cognitive functions that do not depend on motor sequencing. Here we report the results of a study in which we examine the relationship between objectively measured physical activity and (1) explicit relational memory, (2) executive control, and (3) implicit probabilistic sequence learning in a sample of healthy, college-aged adults. The main finding was that physical activity was positively associated with explicit relational memory and executive control (replicating previous research), but negatively associated with implicit learning, particularly in females. These results raise the intriguing possibility that physical activity upregulates some cognitive processes, but downregulates others. Possible implications of this pattern of results for physical health and health habits are discussed.

Rhythm experience and Africana culture trial (REACT!): A culturally salient intervention to promote neurocognitive health, mood, and well-being in older African Americans.

The Rhythm Experience and Africana Culture Trial (REACT!) is a multi-site randomized controlled intervention study designed to examine the efficacy of using African Dance as a form of moderate-intensity physical activity to improve cognitive function in older African Americans. African Americans are almost two times more likely than Caucasians to experience cognitive impairment in late adulthood. This increased risk may be attributed to lower level and quality of education, lower socioeconomic status, and higher prevalence of vascular diseases, type 2 diabetes, hypertension, and obesity, all of which are recognized as risk factors for dementia. Fortunately, interventions targeting cardiovascular health (i.e., physical activity) are associated with improved neurocognitive function and a reduced risk for dementia, so African Americans may be particularly suited for interventions targeting cardiovascular health and cognitive function. Here, we describe a randomized intervention protocol for increasing physical activity in older (65-75years) African Americans. Participants (n=80) at two study locations will be randomized into one of two groups. The treatment group will participate in African Dance three times per week for six months and the control group will receive educational training on Africana history and culture, as well as information about health behaviors, three times per week for six months. If successful, the REACT! study may transform community interventions and serve as a platform and model for testing other populations, age groups, and health outcomes, potentially identifying novel and creative methods for reducing or eliminating health disparities.