PERSISTENT NEUROCOGNITIVE EFFECTS OF CONCUSSION IN MIDDLE-ADULTHOOD

Past studies on the persistent effects of concussions on neurocognitive health have suggested that former athletes in younger and older adulthood are at risk for persistent cognitive impairment, functional neural inefficiency, and loss of structural neural integrity. However, few studies have focused on the effects of concussions on these measures in former athletes in middle-adulthood in order to gain a more complete picture of neurocognitive health in the lifespan of former athletes. The present study utilized a sample of former collegiate athletes to examine neurocognitive health in middle-adulthood via cognitive testing, a functional magnetic resonance imaging scan assessing neural connectivity during a memory binding task, and analysis of white matter integrity along tracts implicated in the neuropathology of concussive and neurodegenerative injury. Based on past research, former athletes with a history of concussions were hypothesized to perform worse on tasks involving high demands on cognitive control and memory, and to show impaired modulation of functional connectivity and compromised structural neural integrity. Results from these analyses showed few differences between athletes with and without a history of concussions: athletes with a history of concussions performed within the normal range on standard cognitive assessments, performed equivalently to athletes with no history of concussions on a task of memory binding, and showed no evidence of reduced white matter integrity. However, former football players with a history of concussions showed inefficient patterns of functional connectivity between a task-relevant and task-irrelevant network. Thus, concussion history may not be consistently associated with widespread neurocognitive dysfunction in middle-adulthood, but it may be associated with inefficient recruitment of cognitive neural networks during a challenging cognitive task. These results have implications for the long-term neurocognitive health of these former football athletes, and raise concerns about the effects of concussion history on more subtle expressions of reduced cognitive reserve throughout the aging process.Doctor of Philosoph

Does Genotype Moderate the Effects of Concussion History and Contact Exposure on Working Memory Processes in Retired Football Players?

Recent studies have linked concussions earlier in life and later memory problems, but little is known about neurocognitive long-term effects of concussion, and whether a genetic risk factor for Alzheimer's Disease, Apolipoprotein-e4 (APOE-e4), might play a role in these long-term effects. In the present study, participants between 50-65 (N=63) were grouped based on concussion history (0-1 or 3+), football exposure (college or college+NFL), and APOE-e4 status (APOE-e4+ or APOE-e4-). Participants completed two batteries of neurocognitive tasks, and performed an fMRI-adapted N-back task. Neurocognitive results revealed selective deficits in memory across all sub-groups, but no differences between the groups. Functional connectivity results suggested that APOE-e4 genotype interacted with concussion and exposure history in accounting for differences in connectivity within a fronto-parietal working memory network. Thus, while there are no behavioral differences between groups, functional connectivity may be altered by the interaction between concussion history, football exposure, and APOE-e4 status.Master of Art

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

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

Global cognitive performance is not influenced by diurnal rhythm: Psychosocial factors and environmental design/Environmental design and technology

Background: There are conflicting reports on the extent to which cognitive performance varies over the course of the day and whether such effects change with advancing age. Method: We used data collected in two longitudinal studies of cognitive reserve: Cognitive Reserve & Reference Ability Neural Network. We reviewed study documents and extracted the time of the day during which an individual’s cognitive battery. Of 543 subjects with available cross‐sectional data, 281 were tested in the AM and 242 in the PM. Mean age was 55 yo. 178 subjects were <50 yo. Multivariate models were used to evaluate the data. Result: We found expected effects of age on cognitive performance, but we found no evidence supporting a difference in either global cognitive performance or of performance in one of the four tested domains in relation to time of day. Further, we saw no evidence for an interaction by age: age did not influence performance differences relative to time of day. Conclusion: We have analyzed a large dataset of prospectively collected data in which we see no evidence that time of day influences results of cognitive testing. This analysis settles an important issue that could have implications on study design when subjects select study visits that are convenient for their schedule

Table_1_Effects of aging on cognitive and brain inter-network integration patterns underlying usual and dual-task gait performance.docx

IntroductionAging 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.MethodsA 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 ResultsUW 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.ConclusionWhile 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.</p