In vivo tau is associated with change in memory and processing speed, but not reasoning, in cognitively unimpaired older adults.

The relationship between tau deposition and cognitive decline in cognitively healthy older adults is still unclear. The tau PET tracer 18F-MK-6240 has shown favorable imaging characteristics to identify early tau deposition in aging. We evaluated the relationship between in vivo tau levels (18F-MK-6240) and retrospective cognitive change over 5 years in episodic memory, processing speed, and reasoning. For tau quantification, a set of regions of interest (ROIs) was selected a priori based on previous literature: (1) total-ROI comprising selected areas, (2) medial temporal lobe-ROI, and (3) lateral temporal lobe-ROI and cingulate/parietal lobe-ROI. Higher tau burden in most ROIs was associated with a steeper decline in memory and speed. There were no associations between tau and reasoning change. The novelty of this finding is that tau burden may affect not only episodic memory, a well-established finding but also processing speed. Our finding reinforces the notion that early tau deposition in areas related to Alzheimer's disease is associated with cognitive decline in cognitively unimpaired individuals, even in a sample with low amyloid-ß pathology.

Effects of aging on cognitive and brain inter-network integration patterns underlying usual and dual-task gait performance.

Introduction: Aging affects the interplay between cognition and gait performance. Neuroimaging studies reported associations between gait performance and structural measures; however, functional connectivity (FC) analysis of imaging data can help to identify dynamic neural mechanisms underlying optimal performance. Here, we investigated the effects on divergent cognitive and inter-network FC patterns underlying gait performance during usual (UW) and dual-task (DT) walking. Methods: A total of 115 community-dwelling, healthy participants between 20 and 80 years were enrolled. All participants underwent comprehensive cognitive and gait assessments in two conditions and resting state functional MRI (fMRI) scans. Inter-network FC from motor-related to 6 primary cognitive networks were estimated. Step-wise regression models tested the relationships between gait parameters, inter-network FC, neuropsychological scores, and demographic variables. A threshold of p < 0.05 was adopted for all statistical analyses. Results: UW was largely associated with FC levels between motor and sustained attention networks. DT performance was associated with inter-network FC between motor and divided attention, and processing speed in the overall group. In young adults, UW was associated with inter-network FC between motor and sustained attention networks. On the other hand, DT performance was associated with cognitive performance, as well as inter-network connectivity between motor and divided attention networks (VAN and SAL). In contrast, the older age group (> 65 years) showed increased integration between motor, dorsal, and ventral attention, as well as default-mode networks, which was negatively associated with UW gait performance. Inverse associations between motor and sustained attention inter-network connectivity and DT performance were observed. Conclusion: While UW relies on inter-network FC between motor and sustained attention networks, DT performance relies on additional cognitive capacities, increased motor, and executive control network integration. FC analyses demonstrate that the decline in cognitive performance with aging leads to the reliance on additional neural resources to maintain routine walking tasks.

Diet moderates the effect of resting state functional connectivity on cognitive function.

Past research suggests modifiable lifestyle factors impact structural and functional measures of brain health, as well as cognitive performance, but no study to date has tested the effect of diet on resting state functional connectivity (rsFC), and its relationship with cognition. The current study tested whether Mediterranean diet (MeDi) moderates the associations between internetwork rsFC and cognitive function. 201 cognitively intact adults 20-80 years old underwent resting state fMRI to measure rsFC among 10 networks, and completed 12 cognitive tasks assessing perceptual speed, fluid reasoning, episodic memory, and vocabulary. Food frequency questionnaires were used to categorize participants into low, moderate, and high MeDi adherence groups. Multivariable linear regressions were used to test associations between MeDi group, task performance, and internetwork rsFC. MeDi group moderated the relationship between rsFC and fluid reasoning for nine of the 10 functional networks' connectivity to all others: higher internetwork rsFC predicted lower fluid reasoning performance in the low MeDi adherence group, but not in moderate and high MeDi groups. Results suggest healthy diet may support cognitive ability despite differences in large-scale network connectivity at rest. Further research is warranted to understand how diet impacts neural processes underlying cognitive function over time.

Self-awareness for financial decision making abilities is linked to right temporal cortical thickness in older adults.

Everyday financial decision making and the awareness of the integrity of one's financial decision making abilities (or financial awareness) are both critical to study in older adults as they can help identify those at risk for making suboptimal financial decisions and prevent financial loss. In the current study, we examined the cognitive and cortical thickness correlates of financial decision making and financial awareness in 59 community-dwelling participants co-enrolled in a larger study (mean age=68.35 years (SD=5.5), mean education=15.91 (SD=2.36), 61% = women, 67% = White, 30% = Black participants). Data from standardized measures of financial decision making and cognition was investigated along with FreeSurfer (v. 5.3) derived thickness regions. Based on metacognitive frameworks, financial awareness was measured along with a well-validated measure of memory awareness. Results revealed that numeracy, executive functioning and vocabulary were associated with financial decision making, whereas in analysis adjusted for financial decision making, memory awareness relative to cognition was most strongly linked to financial awareness. No significant associations between thickness and financial decision making were found. However, both financial and memory awareness were associated with the same right-hemisphere temporal thickness regions underscoring the idea of a common substrate of awareness. Interestingly, our findings converge with the emerging work on financial exploitation in which the right sided temporal regions have been found to play a prominent role. Incorporating the contributing role of self-awareness in various models of financial exploitation will be an important consideration for future studies.

The role of neural flexibility in cognitive aging.

Studies assessing relationships between neural and cognitive changes in healthy aging have shown that a variety of aspects of brain structure and function explain a significant portion of the variability in cognitive outcomes throughout adulthood. Many studies assessing relationships between brain function and cognition have utilized time-averaged, or static functional connectivity methods to explore ways in which brain network organization may contribute to aspects of cognitive aging. However, recent studies in this field have suggested that time-varying, or dynamic measures of functional connectivity, which assess changes in functional connectivity over the course of a scan session, may play a stronger role in explaining cognitive outcomes in healthy young adults. Further, both static and dynamic functional connectivity studies suggest that there may be differences in patterns of brain-cognition relationships as a function of whether or not the participant is performing a task during the scan. Thus, the goals of the present study were threefold: (1) assess whether neural flexibility during both resting as well as task-based scans is related to participant age and cognitive performance in a lifespan aging sample, (2) determine whether neural flexibility moderates relationships between age and cognitive performance, and (3) explore differences in neural flexibility between rest and task. Participants in the study were 386 healthy adults between the ages of 20-80 who provided resting state and/or task-based (Matrix Reasoning) functional magnetic resonance imaging (fMRI) scan data as part of their participation in two ongoing studies of cognitive aging. Neural flexibility measures from both resting and task-based scans reflected the number of times each node changed network assignment, and were averaged both across the whole brain (global neural flexibility) as well as within ten somatosensory/cognitive networks. Results showed that neural flexibility was not related to participant age, and that task-based global neural flexibility, as well as task-based neural flexibility in several networks, tended to be negatively related to reaction times during the Matrix Reasoning task, however these effects did not survive strict multiple comparisons correction. Resting state neural flexibility was not significantly related to either participant age or cognitive performance. Additionally, no neural flexibility measures significantly moderated relationships between participant age and cognitive outcomes. Further, neural flexibility differed as a function of scan type, with resting state neural flexibility being significantly greater than task-based neural flexibility. Thus, neural flexibility measures computed during a cognitive task may be more meaningfully related to cognitive performance across the adult lifespan then resting state measures of neural flexibility.

Longitudinal association between changes in resting-state network connectivity and cognition trajectories: The moderation role of a healthy diet.

Introduction: Healthy diet has been shown to alter brain structure and function and improve cognitive performance, and prior work from our group showed that Mediterranean diet (MeDi) moderates the effect of between-network resting-state functional connectivity (rsFC) on cognitive function in a cross-sectional sample of healthy adults. The current study aimed to expand on this previous work by testing whether MeDi moderates the effects of changes in between- and within-network rsFC on changes in cognitive performance over an average of 5 years. Methods: At baseline and 5-year follow up, 124 adults aged 20-80 years underwent resting state fMRI to measure connectivity within and between 10 pre-defined networks, and completed six cognitive tasks to measure each of four cognitive reference abilities (RAs): fluid reasoning (FLUID), episodic memory, processing speed and attention, and vocabulary. Participants were categorized into low, moderate, and high MeDi groups based on food frequency questionnaires (FFQs). Multivariable linear regressions were used to test relationships between MeDi, change in within- and between-network rsFC, and change in cognitive function. Results: Results showed that MeDi group significantly moderated the effects of change in overall between-network and within-network rsFC on change in memory performance. Exploratory analyses on individual networks revealed that interactions between MeDi and between-network rsFC were significant for nearly all individual networks, whereas the moderating effect of MeDi on the relationship between within-network rsFC change and memory change was limited to a subset of specific functional networks. Discussion: These findings suggest healthy diet may protect cognitive function by attenuating the negative effects of changes in connectivity over time. Further research is warranted to understand the mechanisms by which MeDi exerts its neuroprotective effects over the lifespan.

A framework for identification of a resting-bold connectome associated with cognitive reserve.

The concept of cognitive reserve proposes that specific life experiences result in more flexible or resilient cognitive processing allowing some people to cope better with age- or disease-related brain changes than others. Imaging studies seeking to understand the neural implementation of cognitive reserve have most often used task-related fMRI studies. Using that approach, we recently described a task-invariant cognitive-reserve network whose expression correlated with IQ and that moderated between cortical thickness and cognitive performance. Here we sought to identify a pattern of resting BOLD connectivity related to cognitive reserve. We identified a connectome pattern whose connectivity correlated with IQ in both the derivation sample and a separate replication sample. The majority of the edges showing positive relationships with IQ implicate frontal regions. In the derivation sample, connectivity either moderated the relationship between mean cortical thickness and a set of cognitive outcomes or accounted for unique variance in cognitive performance after accounting for cortical thickness. In a replication sample we found that expression of this connectome correlated significantly with the primary endpoint of IQ, and also accounted for unique variance in cognitive performance beyond cortical thickness. Our findings represent an intermediate level of replication and are unlikely to have arisen purely by type-I error. This connectivity pattern therefore meets some of our theoretical criteria for a cognitive reserve-related network and provides insight into the neural implementation of cognitive reserve. Further, expression of this connectome could potentially be used as a direct measure of cognitive reserve, and as an outcome measure for intervention studies that seek to influence cognitive reserve. Future validation of and re-derivation of the pattern in expanded data sets by our and other groups will lead to further improved estimates of cognitive reserve in resting functional connectivity.

Task-based functional connectivity in aging: How task and connectivity methodology affect discovery of age effects.

INTRODUCTION: Past studies have found that healthy aging has a significant effect on the organization and function of networks in the human brain. Many of these studies have examined how functional connectivity during one task or at rest is affected by aging; however, few studies have systematically examined how the effect of age on functional connectivity may vary as a function of choice of in-scanner task. METHODS: The present study included healthy adults between the ages of 20 and 80 and examined a variety of metrics of functional connectivity during performance of 11 in-scanner tasks, falling into 4 cognitive domains: vocabulary, processing speed, fluid reasoning, and episodic memory. Functional connectivity was assessed at three levels: average correlations within and between 10 networks, system segregation (sensorimotor vs. association networks), and whole-brain graph theory metrics (global efficiency and modularity). RESULTS: Results showed that the effect of age on these metrics differed as a function of task-for example, age had a more consistent effect on functional connectivity metrics computed during fluid reasoning tasks; however, there was less of an effect of age on functional connectivity metrics computed during tasks of episodic memory. Further, some of these measures showed relationships with behavioral performance on the in-scanner task, with different networks playing a role in the different cognitive domains. CONCLUSION: These findings suggest that while aging may be generally associated with reductions in within- and between-network connectivity, system segregation, global efficiency, and modularity, the magnitude and presence of these effects varies by in-scanner task.

Associations between personality and whole-brain functional connectivity at rest: Evidence across the adult lifespan.

INTRODUCTION: Personality is associated with cognitive, emotional, and social functioning, and can play a role in age-related cognitive decline and dementia risk; however, little is known about the brain dynamics underlying personality characteristics, and whether they are moderated by age. METHODS: We investigated the associations between personality and resting-state functional MRI data from 365 individuals across the adult lifespan (20-80 years). Participants completed the 50-item International Personality Item Pool and a resting-state imaging protocol on a 3T MRI scanner. Within-network connectivity values were computed based on predefined networks. Regression analyzes were conducted in order to investigate personality-connectivity associations, as well as moderation by age. All models controlled for potential confounders (such as age, sex, education, IQ, and the other personality traits). RESULTS: We found that openness was positively associated with connectivity in the default-mode network, neuroticism was negatively associated with both the ventral and dorsal attention networks, and agreeableness was negatively associated with the dorsal attention network. In addition, age moderated the association between conscientiousness and the frontoparietal network, indicating that this association become stronger in older age. CONCLUSIONS: Our findings demonstrate that personality is associated with brain connectivity, which may contribute to identifying personality profiles that play a role in protection against or risk for age-related brain changes and dementia.

The Effect of Aging on Resting State Connectivity of Predefined Networks in the Brain.

Recent studies have found a deleterious effect of age on a wide variety of measures of functional connectivity, and some hints at a relationship between connectivity at rest and cognitive functioning. However, few studies have combined multiple functional connectivity methods, or examined them over a wide range of adult ages, to try to uncover which metrics and networks seem to be particularly sensitive to age-related decline across the adult lifespan. The present study utilized multiple resting state functional connectivity methods in a sample of adults from 20-80 years old to gain a more complete understanding of the effect of aging on network function and integrity. Whole-brain results showed that aging results in weakening average within-network connectivity, lower system segregation and local efficiency, and higher participation coefficient. Network-level results suggested that nearly every primary sensory and cognitive network faces some degree of age-related decline, including reduced within-network connectivity, higher network-based participation coefficient, and reduced network-level local efficiency. Further, some of these connectivity metrics showed relationships with cognitive performance. Thus, these results suggest that a multi-method analysis of functional connectivity data may be critical to capture the full effect of aging on the health of brain networks.

Between-network Functional Connectivity Is Modified by Age and Cognitive Task Domain.

Research on the cognitive neuroscience of aging has identified myriad neurocognitive processes that are affected by the aging process, with a focus on identifying neural correlates of cognitive function in aging. This study aimed to test whether internetwork connectivity among six cognitive networks is sensitive to age-related changes in neural efficiency and cognitive functioning. A factor analytic connectivity approach was used to model network interactions during 11 cognitive tasks grouped into four primary cognitive domains: vocabulary, perceptual speed, fluid reasoning, and episodic memory. Results showed that both age and task domain were related to internetwork connectivity and that some of the connections among the networks were associated with performance on the in-scanner tasks. These findings demonstrate that internetwork connectivity among several cognitive networks is not only affected by aging and task demands but also shows a relationship with task performance. As such, future studies examining internetwork connectivity in aging should consider multiple networks and multiple task conditions to better measure dynamic patterns of network flexibility over the course of cognitive aging.

Effects of Career Duration, Concussion History, and Playing Position on White Matter Microstructure and Functional Neural Recruitment in Former College and Professional Football Athletes.

Purpose To better understand the relationship between exposure to concussive and subconcussive head impacts, white matter integrity, and functional task-related neural activity in former U.S. football athletes. Materials and Methods Between 2011 and 2013, 61 cognitively unimpaired former collegiate and professional football players (age range, 52-65 years) provided informed consent to participate in this cross-sectional study. Participants were stratified across three crossed factors: career duration, concussion history, and primary playing position. Fractional anisotropy (FA) and blood oxygen level-dependent (BOLD) percent signal change (PSC) were measured with diffusion-weighted and task-related functional magnetic resonance imaging, respectively. Analyses of variance of FA and BOLD PSC were used to determine main or interaction effects of the three factors. Results A significant interaction between career duration and concussion history was observed; former college players with more than three concussions had lower FA in a broadly distributed area of white matter compared with those with zero to one concussion (t29 = 2.774; adjusted P = .037), and the opposite was observed for former professional players (t29 = 3.883; adjusted P = .001). A separate interaction between concussion history and position was observed: Nonspeed players with more than three concussions had lower FA in frontal white matter compared with those with zero to one concussion (t25 = 3.861; adjusted P = .002). Analysis of working memory-task BOLD PSC revealed a similar interaction between concussion history and position (all adjusted P < .004). Overall, former players with lower FA tended to have lower BOLD PSC across three levels of a working memory task. Conclusion Career duration and primary playing position seem to modify the effects of concussion history on white matter structure and neural recruitment. The differences in brain structure and function were observed in the absence of clinical impairment, which suggested that multimodal imaging may provide early markers of onset of traumatic neurodegenerative disease. © RSNA, 2017 Online supplemental material is available for this article.

Estimating Contact Exposure in Football Using the Head Impact Exposure Estimate.

Over the past decade, there has been significant debate regarding the effect of cumulative subconcussive head impacts on short and long-term neurological impairment. This debate remains unresolved, because valid epidemiological estimates of athletes' total contact exposure are lacking. We present a measure to estimate the total hours of contact exposure in football over the majority of an athlete's lifespan. Through a structured oral interview, former football players provided information related to primary position played and participation in games and practice contacts during the pre-season, regular season, and post-season of each year of their high school, college, and professional football careers. Spring football for college was also included. We calculated contact exposure estimates for 64 former football players (n = 32 college football only, n = 32 professional and college football). The head impact exposure estimate (HIEE) discriminated between individuals who stopped after college football, and individuals who played professional football (p < 0.001). The HIEE measure was independent of concussion history (p = 0.82). Estimating total hours of contact exposure may allow for the detection of differences between individuals with variation in subconcussive impacts, regardless of concussion history. This measure is valuable for the surveillance of subconcussive impacts and their associated potential negative effects.

Exercise reinforcement, stress, and ß-endorphins: an initial examination of exercise in anabolic-androgenic steroid dependence.

BACKGROUND: Anabolic-androgenic steroids (AASs) are abused primarily in the context of intense exercise and for the purposes of increasing muscle mass as opposed to drug-induced euphoria. AASs also modulate the HPA axis and may increase the reinforcing value of exercise through changes to stress hormone and endorphin release. To test this hypothesis, 26 adult males drawn from a larger study on AAS use completed a progressive ratio task designed to examine the reinforcing value of exercise relative to financial reinforcer. METHOD: Sixteen experienced and current users (8 on-cycle, 8 off-cycle) and 10 controls matched on quantity×frequency of exercise, age, and education abstained from exercise for 24 h prior to testing and provided 24-h cortisol, plasma cortisol, ACTH, ß-endorphin samples, and measures of mood, compulsive exercise, and body image. RESULTS: Between group differences indicated that on-cycle AAS users had the highest ß-endorphin levels, lowest cortisol levels, higher ACTH levels than controls. Conversely, off-cycle AAS users had the highest cortisol and ACTH levels, but the lowest ß-endorphin levels. Exercise value was positively correlated with ß-endorphin and symptoms of AAS dependence. CONCLUSION: The HPA response to AASs may explain why AASs are reinforcing in humans and exercise may play a key role in the development of AAS dependence.

Gay male attraction toward muscular men: does mating context matter?

The purpose of this study was to examine gay men's perceived attractiveness of male figures based on short-term and long-term partner contexts. A sample of 190 gay adult men rated the attractiveness of line-drawings depicting male figures varying systematically in muscularity and body fat percentage in both short-term and long-term dating contexts. Mixed effects modeling was used to estimate the effects of figure (muscularity and body fat), dating context (short-term vs. long-term), and individual rater characteristics on attractiveness ratings. Results indicated that figure muscularity and body-fat had significant non-linear (i.e., quadratic) relationships with attractiveness ratings, and short-term dating context was associated with more discriminating ratings of attractiveness. Interactions between individual characteristics and figure characteristics indicated that the more available the individual and lower body fat, the more discriminating they were in ratings of attractiveness. The implications for future investigations considering both object and observer characteristics of attractiveness preferences are discussed.