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.

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.

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.

Motor sequence learning-induced neural efficiency in functional brain connectivity.

Previous studies have shown the functional neural circuitry differences before and after an explicitly learned motor sequence task, but have not assessed these changes during the process of motor skill learning. Functional magnetic resonance imaging activity was measured while participants (n=13) were asked to tap their fingers to visually presented sequences in blocks that were either the same sequence repeated (learning block) or random sequences (control block). Motor learning was associated with a decrease in brain activity during learning compared to control. Lower brain activation was noted in the posterior parietal association area and bilateral thalamus during the later periods of learning (not during the control). Compared to the control condition, we found the task-related motor learning was associated with decreased connectivity between the putamen and left inferior frontal gyrus and left middle cingulate brain regions. Motor learning was associated with changes in network activity, spatial extent, and connectivity.

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.

Genetic Risk Score Predicts Late-Life Cognitive Impairment.

Introduction. A family history of Alzheimer's disease is a significant risk factor for its onset, but the genetic risk associated with possessing multiple risk alleles is still poorly understood. Methods. In a sample of 95 older adults (Mean age = 75.1, 64.2% female), we constructed a genetic risk score based on the accumulation of risk alleles in BDNF, COMT, and APOE. A neuropsychological evaluation and consensus determined cognitive status (44 nonimpaired, 51 impaired). Logistic regression was performed to determine whether the genetic risk score predicted cognitive impairment above and beyond that associated with each gene. Results. An increased genetic risk score was associated with a nearly 4-fold increased risk of cognitive impairment (OR = 3.824, P = .013) when including the individual gene polymorphisms as covariates in the model. Discussion. A risk score combining multiple genetic influences may be more useful in predicting late-life cognitive impairment than individual polymorphisms.