Regina L. Leckie

Physical activity, fitness, and gray matter volume

In this review, we explore the association among physical activity, cardiorespiratory fitness, and exercise on gray matter volume in older adults. We conclude that higher cardiorespiratory fitness levels are routinely associated with greater gray matter volume in the prefrontal cortex and hippocampus and less consistently in other regions. We also conclude that physical activity is associated with greater gray matter volume in the same regions that are associated with cardiorespiratory fitness including the prefrontal cortex and hippocampus. Some heterogeneity in the literature may be explained by effect moderation by age, stress, or other factors. Finally, we report promising results from randomized exercise interventions that suggest that the volume of the hippocampus and prefrontal cortex remain pliable and responsive to moderate intensity exercise for 6 months-1 year. Physical activity appears to be a propitious method for influencing gray matter volume in late adulthood, but additional well-controlled studies are necessary to inform public policies about the potential protective or therapeutic effects of exercise on brain volume.

fMRI reveals reciprocal inhibition between social and physical cognitive domains.

Two lines of evidence indicate that there exists a reciprocal inhibitory relationship between opposed brain networks. First, most attention-demanding cognitive tasks activate a stereotypical set of brain areas, known as the task-positive network and simultaneously deactivate a different set of brain regions, commonly referred to as the task negative or default mode network. Second, functional connectivity analyses show that these same opposed networks are anti-correlated in the resting state. We hypothesize that these reciprocally inhibitory effects reflect two incompatible cognitive modes, each of which may be directed towards understanding the external world. Thus, engaging one mode activates one set of regions and suppresses activity in the other. We test this hypothesis by identifying two types of problem-solving task which, on the basis of prior work, have been consistently associated with the task positive and task negative regions: tasks requiring social cognition, i.e., reasoning about the mental states of other persons, and tasks requiring physical cognition, i.e., reasoning about the causal/mechanical properties of inanimate objects. Social and mechanical reasoning tasks were presented to neurologically normal participants during fMRI. Each task type was presented using both text and video clips. Regardless of presentation modality, we observed clear evidence of reciprocal suppression: social tasks deactivated regions associated with mechanical reasoning and mechanical tasks deactivated regions associated with social reasoning. These findings are not explained by self-referential processes, task engagement, mental simulation, mental time travel or external vs. internal attention, all factors previously hypothesized to explain default mode network activity. Analyses of resting state data revealed a close match between the regions our tasks identified as reciprocally inhibitory and regions of maximal anti-correlation in the resting state. These results indicate the reciprocal inhibition is not attributable to constraints inherent in the tasks, but is neural in origin. Hence, there is a physiological constraint on our ability to simultaneously engage two distinct cognitive modes. Further work is needed to more precisely characterize these opposing cognitive domains.

BDNF mediates improvements in executive function following a 1-year exercise intervention

Executive function declines with age, but engaging in aerobic exercise may attenuate decline. One mechanism by which aerobic exercise may preserve executive function is through the up-regulation of brain-derived neurotropic factor (BDNF), which also declines with age. The present study examined BDNF as a mediator of the effects of a 1-year walking intervention on executive function in 90 older adults (mean age = 66.82). Participants were randomized to a stretching and toning control group or a moderate intensity walking intervention group. BDNF serum levels and performance on a task-switching paradigm were collected at baseline and follow-up. We found that age moderated the effect of intervention group on changes in BDNF levels, with those in the highest age quartile showing the greatest increase in BDNF after 1-year of moderate intensity walking exercise (p = 0.036). The mediation analyses revealed that BDNF mediated the effect of the intervention on task-switch accuracy, but did so as a function of age, such that exercise-induced changes in BDNF mediated the effect of exercise on task-switch performance only for individuals over the age of 71. These results demonstrate that both age and BDNF serum levels are important factors to consider when investigating the mechanisms by which exercise interventions influence cognitive outcomes, particularly in elderly populations.

Visioning in the brain: an fMRI study of inspirational coaching and mentoring.

Effective coaching and mentoring is crucial to the success of individuals and organizations, yet relatively little is known about its neural underpinnings. Coaching and mentoring to the Positive Emotional Attractor (PEA) emphasizes compassion for the individuals hopes and dreams and has been shown to enhance a behavioral change. In contrast, coaching to the Negative Emotional Attractor (NEA), by focusing on externally defined criteria for success and the individuals weaknesses in relation to them, does not show sustained change. We used fMRI to measure BOLD responses associated with these two coaching styles. We hypothesized that PEA coaching would be associated with increased global visual processing and with engagement of the parasympathetic nervous system (PNS), while the NEA coaching would involve greater engagement of the sympathetic nervous system (SNS). Regions showing more activity in PEA conditions included the lateral occipital cortex, superior temporal cortex, medial parietal, subgenual cingulate, nucleus accumbens, and left lateral prefrontal cortex. We relate these activations to visioning, PNS activity, and positive affect. Regions showing more activity in NEA conditions included medial prefrontal regions and right lateral prefrontal cortex. We relate these activations to SNS activity, self-trait attribution and negative affect.

Potential moderators of physical activity on brain health.

Age-related cognitive decline is linked to numerous molecular, structural, and functional changes in the brain. However, physical activity is a promising method of reducing unfavorable age-related changes. Physical activity exerts its effects on the brain through many molecular pathways, some of which are regulated by genetic variants in humans. In this paper, we highlight genes including apolipoprotein E (APOE), brain derived neurotrophic factor (BDNF), and catechol-O-methyltransferase (COMT) along with dietary omega-3 fatty acid, docosahexaenoic acid (DHA), as potential moderators of the effect of physical activity on brain health. There are a growing number of studies indicating that physical activity might mitigate the genetic risks for disease and brain dysfunction and that the combination of greater amounts of DHA intake with physical activity might promote better brain function than either treatment alone. Understanding whether genes or other lifestyles moderate the effects of physical activity on neurocognitive health is necessary for delineating the pathways by which brain health can be enhanced and for grasping the individual variation in the effectiveness of physical activity interventions on the brain and cognition. There is a need for future research to continue to assess the factors that moderate the effects of physical activity on neurocognitive function.

Omega-3 fatty acids moderate effects of physical activity on cognitive function

Greater amounts of physical activity (PA) and omega-3 fatty acids have both been independently associated with better cognitive performance. Because of the overlapping biological effects of omega-3 fatty acids and PA, fatty acid intake may modify the effects of PA on neurocognitive function. The present study tested this hypothesis by examining whether the ratio of serum omega-6 to omega-3 fatty acid levels would moderate the association between PA and executive and memory functions in 344 participants (Mean age=44.42 years, SD=6.72). The Paffenbarger Physical Activity Questionnaire (PPAQ), serum fatty acid levels, and performance on a standard neuropsychological battery were acquired on all subjects. A principal component analysis reduced the number of cognitive outcomes to three factors: n-back working memory, Trail Making test, and Logical Memory. We found a significant interaction between PA and the ratio of omega-6 to omega-3 fatty acid serum levels on Trail Making performance and n-back performance, such that higher amounts of omega-3 levels offset the deleterious effects of lower amounts of PA. These effects remained significant in a subsample (n=299) controlling for overall dietary fat consumption. There were no significant additive or multiplicative benefits of higher amounts of both omega-3 and PA on cognitive performance. Our results demonstrate that a diet high in omega-3 fatty acids might mitigate the effect of lower levels of PA on cognitive performance. This study illuminates the importance of understanding dietary and PA factors in tandem when exploring their effects on neurocognitive health.

Measuring Physical Activity Using Accelerometry in a Community Sample with Dementia

To the Editor: Physical activity (PA) reduces the risk of dementia1 and extends the lifespan.2 Although most prospective studies assess PA according to self-report, these measures are limited in scope and susceptible to social desirability biases. Despite the prospect that PA may alleviate cognitive impairment, few studies have objectively assessed PA in cognitively impaired individuals. Herein the feasibility of objectively measuring PA and adherence to wearing an activity-monitoring device in a cognitively impaired sample was assessed. Participants were recruited from the Pittsburgh Alzheimers Disease Research Center (ADRC). Details of clinical adjudication have been described.3,4 Participants and care-givers signed an informed consent/assent approved by the University of Pittsburgh institutional review board and were remunerated

Photoperiod is associated with hippocampal volume in a large community sample

50. A control group of 28 cognitively normal adults, age matched to the impaired group, were also enrolled. Information on the number of subjects recruited, consented, and returning the device was documented. Participants were given a PA monitoring device (BodyMedia, SenseWear, Pittsburgh, PA), an accelerometer designed to be worn on the arm, at the time of their ADRC visit and were asked to return the device in a prepaid envelope after 7 days of data collection. Caregivers were required to be present at the ADRC visit, so results are reported only from subjects with caregivers. Caregivers were important in maintaining adherence and were provided information and instructions on the device. The device collected information on number of steps, estimates of metabolic equivalent of tasks (METs), and active energy expenditure (EE) and has been extensively validated.5 Minutes of moderate and intense PA were estimated from standard criteria based on METs. Fifty-two cognitively impaired individuals were approached, and 47 (90.4%) were recruited. At least 3 days of accelerometry are necessary for assessing PA.6 Of the 39 participants (83%) completing the study with at least 3 days of data, 26 were diagnosed with Alzheimers disease (AD) and 13 with mild cognitive impairment (MCI). Nine lived alone (4 AD, 5 MCI) and 30 with a caregiver. The AD group was less educated than the MCI or control group (P = .005) and slightly older than the MCI group (P = .05) (Table 1). Table 1 Physical Activity and Demographic Information According to Group Of the eight cognitively impaired individuals not completing the study, four were diagnosed with AD, three with MCI, and one with impairment without subjective memory complaints. Those not completing the study (mean age 78.2 ± 9.5) were older but statistically equivalent to those finishing the study (mean age 74.2 ± 10.3; P = .70). The reasons for not finishing the study were that the monitoring device was lost or not returned (n = 2), was returned without data (n = 2), was returned but was worn for fewer than 3 days (n = 3), and was returned prematurely for unknown reasons (n = 1). The cognitively normal adults (n = 28) had a 100% adherence rate for wearing the device for at least 3 days. The daily percentage of time wearing the device did not differ between the cognitively normal and impaired groups (t(1,65) = 0.89; P = .40), nor did it differ between the diagnostic subgroups (t(1,37) = 0.81; P = .42). This study demonstrates that it is feasible to use PA monitoring devices in individuals with cognitive impairment. There was interest in and a commitment to wearing the device for at least 3 days, and most wore the device for 7 days (Table 1). Demonstrating feasibility of PA monitoring devices in a cognitively impaired population is fundamental for designing randomized trials of PA, but despite the high level of interest in participating, adherence was lower in the cognitively impaired population (83%) than in the cognitively normal adults (100%). These numbers should be considered when designing future trials and power analyses to assess adherence and sample sizes. PA monitoring devices have been validated in samples across the lifespan7 and are used to assess risk of falls,8 quality of life,9 and sleep10 in elderly adults. The current study demonstrated the feasibility of objectively assessing PA in a community sample of individuals with dementia. Given the cross-sectional nature of the study, the small sample size, and the limited information on comorbidities, it will be necessary for future studies to systematically and comprehensively assess and control for potential confounders between groups. Nonetheless, this study demonstrates that there is interest in using this type of technology to monitor activity and lifestyle in cognitively impaired individuals. Future studies could use this technology for monitoring activity, sleep, and physical exertion in elderly adults with the aim of developing non-pharmacological interventions to enhance cognition or prevent further cognitive decline.

Education mitigates age-related decline in N-Acetylaspartate levels.

Although animal research has demonstrated seasonal changes in hippocampal volume, reflecting seasonal neuroplasticity, seasonal differences in human hippocampal volume have yet to be documented. Hippocampal volume has also been linked to depressed mood, a seasonally varying phenotype. Therefore, we hypothesized that seasonal differences in day‐length (i.e., photoperiod) would predict differences in hippocampal volume, and that this association would be linked to low mood. Healthy participants aged 30–54 (M = 43; SD = 7.32) from the University of Pittsburgh Adult Health and Behavior II project (n = 404; 53% female) were scanned in a 3T MRI scanner. Hippocampal volumes were determined using an automated segmentation algorithm using FreeSurfer. A mediation model tested whether hippocampal volume mediated the relationship between photoperiod and mood. Secondary analyses included seasonally fluctuating variables (i.e., sleep and physical activity) which have been shown to influence hippocampal volume. Shorter photoperiods were significantly associated with higher BDI scores (R2 = 0.01, β = −0.12, P = 0.02) and smaller hippocampal volumes (R2 = 0.40, β = 0.08, P = 0.04). However, due to the lack of an association between hippocampal volume and Beck Depression Inventory scores in the current sample, the mediation hypothesis was not supported. This study is the first to demonstrate an association between season and hippocampal volume. These data offer preliminary evidence that human hippocampal plasticity could be associated with photoperiod and indicates a need for longitudinal studies.

Physical activity and hippocampal volume in middle-aged patients with type 1 diabetes

Greater educational attainment is associated with better neurocognitive health in older adults and is thought to reflect a measure of cognitive reserve. In vivo neuroimaging tools have begun to identify the brain systems and networks potentially responsible for reserve.