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Individualized and precision medicine approaches to exercise for cognitive and brain health in aging have the potential to improve intervention efficacy. Predicting adherence to an exercise intervention in older adults prior to its commencement will allow for adaptive and optimized approaches that could save time (no need to demonstrate failure before changing course) and money (cost of de-implementing approaches that do not work for certain individuals) which ultimately could improve health outcomes (e.g., preventative medicine approaches prior to the onset of symptoms). Individual differences in brain structure and function in older adults are potential proxies of brain and brain reserve or maintenance and may provide strong predictions of adherence. We hypothesized that brain-based measures would predict adherence to a six-month randomized controlled trial of exercise in older adults, alone and in combination with psychosocial, cognitive and health measures. In 131 older adults (aged 65.79 ± 4.65 years, 63% female) we found, using regularized elastic net regression within a nested cross-validation framework, that brain structure (cortical thickness and cortical surface area) in somatosensory, inferior temporal, and inferior frontal regions and functional connectivity (degree count) in primary information processing (somatosensory, visual), executive control, default, and attentional networks, predicted exercise adherence (R2 = 0.15, p < 0.001). Traditional survey and clinical measures such as gait and walking self-efficacy, biological sex and perceived stress also predicted adherence (R2 = 0.06, p = 0.001) but a combined multimodal model achieved the highest predictive strength (R2 = 0.22, p

BackgroundIndividuals with multiple sclerosis (MS) are vulnerable to deficits in working memory, and the search for neural correlates of working memory in circumscribed areas has yielded inconclusive findings. Given the widespread neural alterations observed in MS, predictive modeling approaches that capitalize on whole-brain connectivity may better capture individual-level working memory in this population.MethodsHere, we applied connectome-based predictive modeling to functional MRI data from working memory tasks in two independent samples with relapsing-remitting MS. In the internal validation sample (ninternal = 36), functional connectivity data were used to train a model through cross-validation to predict accuracy on the Paced Visual Serial Addition Test, a gold-standard measure of working memory in MS. We then tested its ability to predict performance on the N-back working memory task in the external validation sample (nexternal = 36).ResultsThe resulting model successfully predicted working memory in the internal validation sample but did not extend to the external sample. We also tested the generalizability of an existing model of working memory derived in healthy young adults to people with MS. It showed successful prediction in both MS samples, demonstrating its translational potential. We qualitatively explored differences between the healthy and MS models in intra- and inter-network connectivity amongst canonical networks.DiscussionThese findings suggest that connectome-based predictive models derived in people with MS may have limited generalizability. Instead, models identified in healthy individuals may offer superior generalizability to clinical samples, such as MS, and may serve as more useful targets for intervention.Impact StatementWorking memory deficits in people with multiple sclerosis have important consequence for employment, leisure, and daily living activities. Identifying a functional connectivity-based marker that accurately captures individual differences in working memory may offer a useful target for cognitive rehabilitation. Manglani et al. demonstrate machine learning can be applied to whole-brain functional connectivity data to identify networks that predict individual-level working memory in people with multiple sclerosis. However, existing network-based models of working memory derived in healthy adults outperform those identified in multiple sclerosis, suggesting translational potential of brain networks derived in large, healthy samples for predicting cognition in multiple sclerosis.

Early detection of Alzheimer’s disease (AD) is a necessity as prognosis is poor upon symptom onset. Although previous work diagnosing AD from protein-based biomarkers has been encouraging, cerebrospinal (CSF) biomarker measurement of AD proteins requires invasive lumbar puncture, whereas assessment of direct accumulation requires radioactive substance exposure in positron emission tomography (PET) imaging. Functional magnetic resonance imaging (fMRI)-based neuromarkers, offers an alternative, especially those built by capitalizing on variance distributed across the entire human connectome. In this study, we employed connectome-based predictive modeling (CPM) to build a model of functional connections that would predict CSF p-tau/Aβ42 (PATH-fc model) in individuals diagnosed with Mild Cognitive Impairment (MCI) and AD dementia. fMRI, CSF-based biomarker data, and longitudinal data from neuropsychological testing from the Alzheimer’s Disease NeuroImaging Initiative (ADNI) were utilized to build the PATH-fc model. Our results provide support for successful in-sample fit of the PATH-fc model in predicting AD pathology in MCI and AD dementia individuals. The PATH-fc model, distributed across all ten canonical networks, additionally predicted cognitive decline on composite measures of global cognition and executive functioning. Our highly distributed pathology-based model of functional connectivity disruptions had a striking overlap with the spatial affinities of amyloid and tau pathology, and included the default mode network as the hub of such network-based disruptions in AD. Future work validating this model in other external datasets, and to midlife adults and older adults with no known diagnosis, will critically extend this neuromarker development work using fMRI.Significance StatementAlzheimer’s disease (AD) is clinical-pathological syndrome with multi-domain amnestic symptoms considered the hallmark feature of the disease. However, accumulating evidence from autopsy studies evince support for the onset of pathophysiological processes well before the onset of symptoms. Although CSF- and PET-based biomarkers provide indirect and direct estimates of AD pathology, both methodologies are invasive. In here, we implemented a supervised machine learning algorithm – connectome-based predictive modeling – on fMRI data and found support for a whole-brain model of functional connectivity to predict AD pathology and decline in cognitive functioning over a two-year period. Our study provides support for AD pathology dependent functional connectivity disturbances in large-scale functional networks to influence the trajectory of key cognitive domains in MCI and AD patients.

INTRODUCTIONThe most well-studied biomarkers in AD are CSF amyloid beta-42 (Aβ42), tau, p-tau, and the ratio p-tau/Aβ42. The ratiometric measure of p-tau/Aβ42 shows the best diagnostic accuracy, and correlates reliably with metrics of cognition in unimpaired participants. However, no study has examined the impact of the CSF p-tau/Aβ42 ratio in predicting cognitive decline in both healthy and AD individuals in one sample. The goal of this study was to examine whether CSF-based p-tau/Aβ42 predicts changes in global cognitive functioning, episodic memory, and executive functioning over a two-year period in cognitively impaired older adults (CU), and in individuals with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD).METHODSThis study involves secondary analysis of data from 1215 older adults available in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neuropsychological variables, collected at baseline, 6-month, 12-month, and 24-month follow-ups, included the Preclinical Alzheimer’s Cognitive Composite (PACC) to assess global cognitive functioning, ADNI-MEM to assess episodic memory functioning, and ADNI-EF to assess executive functioning. Linear mixed models were constructed to examine the effect of CSF p-tau/Aβ42, diagnostic group, and change over time (baseline, 6-month, 12-month, and 24-month) on cognitive scores.RESULTSCSF p-tau/Aβ42 ratios predicted worsening cognitive impairment, both on global cognition and episodic memory in individuals with MCI and AD, but not in CU older adults and predicted decline in executive functioning for all three diagnostic groups.DISCUSSIONOur study, including CU, MCI, and AD individuals, provides evidence for differential cognitive consequences of accumulated AD pathology based on diagnostic groups.

Objective The aim of this preregistered, secondary analysis of a pilot randomized controlled trial (NCT02717429) was to compare the impact of 4-week mindfulness-based training and adaptive cognitive training, with a waitlist control condition, on processing speed and working memory in people with multiple sclerosis (PwMS). Method Sixty-one PwMS were randomized to mindfulness-based training (MBT), adaptive computerized cognitive training (aCT), or a waitlist (WL) control group and completed the Brief Repeatable Battery of Neuropsychological Tests at pre- and posttraining. Training-related changes on the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT) were the primary outcomes of interest. Baseline cognitive status was examined as a moderator of treatment gains. Practice time, change in aCT game difficulty, and rate of change in state awareness across MBT were assessed as correlates of cognitive gains. Findings Compared with aCT and WL, mindfulness training significantly improved processing speed (ηp² = .14). Baseline cognitive status did not moderate change in processing speed (ηp² = .005) or working memory (ηp² = .014). Practice time and change in game difficulty were not significantly correlated with cognitive gains (all ps > .49). In the MBT group, rate of change in awareness was significantly associated with improvement in working memory (ρ = .52, p = .04). Conclusions In PwMS, 4 weeks of mindfulness meditation training improved processing speed above and beyond aCT and WL. More rapid change in awareness during mindfulness training may be associated with greater gains in working memory. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Objectives: Aging is associated with declines in performance on certain laboratory tasks of attentional control. However, older adults tend to report greater mindful, present-moment attention and less mind-wandering (MW) than young adults. For older adults, high levels of these traits may be protective for attentional performance. This study examined age-related differences in global (i.e., full-task) and local (i.e., pre-MW) attentional control and explored the variance explained by MW and mindfulness. Methods: Cross-sectional comparisons were conducted on data from a previously reported sample of 75 older adults (ages, 60–75 years) and a new sample of 50 young adults (ages, 18–30 years). All participants completed a Go/No-Go task and a Continuous Performance Task with quasi-random MW probes. Results: There were few age-related differences in attentional control. Although MW was not associated with decrements in global performance, local performance measures revealed deleterious effects of MW, which were present across age groups. Older adults reported higher trait mindfulness and less MW than young adults, and these variables helped explain the lack of observed age-related differences in attentional control. Conclusions: Individual differences in dispositional mindfulness and MW propensity explain important variance in attentional performance across age. Increasing present-moment focus and reducing lapses in attention represent important targets for cognitive rehabilitation interventions. (JINS, 2018, 24, 876–888)

BACKGROUND: High levels of circulating proinflammatory cytokines are characteristic of inflammaging, a term coined to describe age-related chronic systemic inflammation involved in the etiology of many age-related disorders including nonhealing wounds. Some studies have shown that supplementing diets with n-3 polyunsaturated fatty acids (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) lowers systemic levels of key proinflammatory cytokines associated with inflammaging. However, findings from the few studies that have focused exclusively on older adults are inconclusive. As such, the objective of this randomized controlled study was to test the effects of EPA+DHA therapy on circulating levels of proinflammatory cytokines in adults in middle to late adulthood. METHODS: Plasma levels of fatty acids and interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were measured in 35 participants with chronic venous leg ulcers (mean age: 60.6 years) randomnly assigned to 8 weeks of EPA+DHA therapy (2.5 g/d) or placebo therapy. RESULTS: EPA+DHA therapy had a significant lowering effect on levels of IL-6, IL-1β and TNF-α after 4 weeks of therapy and an even greater lowering effect after 8 weeks of therapy. Further, after adjusting for baseline difference, the treatment group had significantly lower levels of IL-6 (p = .008), IL-1β (p < .001), and TNF-α (p < .001) at Week 4 and at Week 8 [IL-6 (p = .007), IL-1β (p < .001), and TNF-α (p < .001)] compared to the control group. CONCLUSION: Adults in middle to late adulthood receiving EPA+DHA therapy demonstrated significantly greater reductions in circulating levels of proinflammatory cytokines compared with those receiving placebo therapy. EPA+DHA therapy may be an effective low-risk dietary intervention for assuaging the harmful effects of inflammaging.

Loneliness, an interpersonally stressful state of perceived social isolation, enhances risk for cognitive difficulties. For example, loneliness has been linked to the development of cognitive impairment and dementia among older adults. Lonelier adults ages 65 and above experienced more cognitive impairment, as assessed by the Abbreviated Mental Test, than those who were less lonely (1). Lonelier adults ages 75 and older had larger cognitive declines over 10 years than their less lonely counterparts, as measured by the Mini-Mental State Examination (2). In addition, lonelier adults who were an average of 81 years old were twice as likely to develop Alzheimer’s disease during a 6-year period compared with those who were less lonely (3). Recent research has also addressed the relationship between loneliness and specific types of cognitive function. A report from the English Longitudinal Study of Ageing demonstrated that lonelier adults who were an average of 65 years old had larger declines in verbal episodic memory, but not verbal fluency, over a 4-year period compared with those who were less lonely (4). Accordingly, it is important to understand the factors that could reduce loneliness-related cognitive difficulties over time, particularly memory problems, which lonely people experience as adults. The current study investigated whether omega-3 supplementation could alleviate loneliness-related cognitive declines. Mechanistically, omega-3 polyunsaturated fatty acids (PUFAs), commonly found in oily fish, are essential to normal brain development and maintenance. For example, omega-3 PUFAs help prevent neuronal apoptosis (5,6). Omega-3 PUFAs also reduce inflammation (7), which could have downstream effects on cognitive function (8). Epidemiological and observational studies of dietary intake support the link between omega-3 and cognitive function, particularly global indices of cognitive impairment; people with higher dietary intake of omega-3 had a reduced risk of new-onset dementia, and less global cognitive decline over time than people with lower omega-3 intake (9–11). A large population-based study demonstrated that older adults who ate more fish had better cognitive performance, as measured by a neuropsychological test battery, than those who ate less fish (12). Adults who reported higher marine-based PUFA intake had better overall cognitive function, as reflected by a better composite score across the Kendrick Object Learning Test, the Trail Making Test (Part A), and a variety of other cognitive tests, compared with those who reported lower marine-based PUFA intake (13). Indeed, a recent meta-analysis concluded that people with high adherence to a typical Mediterranean diet, which is high in fish, had a lower risk of both mild and advanced global cognitive impairment than their less adherent counterparts (14). Studies examining the cognitive benefits of omega-3 supplementation also support the link between omega-3 and cognition, although the effects are much less consistent. A number of randomized controlled trials (RCTs) demonstrate better cognitive function, including less global cognitive impairment and better attention, in omega-3 supplemented groups compared with placebo (15–17). In addition, healthy adults who received an omega-3 supplement were faster at both working and episodic memory tasks than those who received a placebo (18). Although some studies report null effects (e.g., 19,20), the supplementation literature suffers from methodological inconsistencies such as varied supplementation doses, supplementation regimen lengths, and sample characteristics (e.g., cognitively healthy versus Alzheimer’s disease patients) which could contribute to the contradictory results. Emerging evidence from the omega-3 literature suggests that supplementation improves cognitive function for people experiencing mild cognitive problems. For instance, a recent meta-analysis of 10 RCTs concluded that immediate verbal recall, attention, and processing speed were better among people receiving an omega-3 supplement compared with placebo, but only for people experiencing mild cognitive impairment (21). No supplementation effects were found for cognitively healthy participants or people with Alzheimer’s disease. Similarly, among healthy older adults with age-related cognitive decline, those in the omega-3 supplementation group had better visuospatial and immediate and delayed verbal memory compared with their counterparts in the placebo condition; there was no effect of supplementation on executive function or working memory (17). In addition, a recent RCT demonstrated that among adults with mild cognitive impairment, those who received an omega-3 supplement had improved working memory, immediate visual episodic memory, and delayed verbal episodic memory compared with those who received a placebo (22). The present study is a secondary analysis of a RCT assessing the anti-inflammatory effects of omega-3 supplementation (7; ClinicalTrials.gov identifier: NCT00385723). The consort diagram and other RCT-related documents are available in the primary report. This study explored the impact of loneliness and omega-3 supplementation on secondary outcomes in our RCT: verbal episodic memory, working memory, executive function, and verbal fluency/processing speed. Taken together, prior research suggests that lonely adults may develop memory difficulties over time and omega-3 intake could lessen these risks. However, the existing literature linking loneliness, omega-3 supplementation, and cognitive function is in its infancy and many questions remain unanswered. Accordingly, exploratory questions and analyses are needed to begin joining these diverse literatures. The clearest preliminary hypothesis derived from prior research was that lonelier participants would have poorer verbal episodic memory than less lonely participants, and that omega-3 supplementation would attenuate these effects. We also explored the effects of loneliness and omega-3 supplementation on working memory, executive function, and verbal fluency/processing speed.

Multiple sclerosis (MS) is a neurodegenerative, inflammatory disease of the central nervous system, resulting in physical and cognitive disturbances. The goal of the current study was to examine the association between network integrity and composite measures of cognition and disease severity in individuals with relapsing-remitting MS (RRMS), relative to healthy controls. All participants underwent a neuropsychological and neuroimaging session, where resting-state data was collected. Independent component analysis and dual regression were employed to examine network integrity in individuals with MS, relative to healthy controls. The MS sample exhibited less connectivity in the motor and visual networks, relative to healthy controls, after controlling for group differences in gray matter volume. However, no alterations were observed in the frontoparietal, executive control, or default-mode networks, despite previous evidence of altered neuronal patterns during tasks of exogenous processing. Whole-brain, voxel-wise regression analyses with disease severity and processing speed composites were also performed to elucidate the brain-behavior relationship with neuronal network integrity. Individuals with higher levels of disease severity demonstrated reduced intra-network connectivity of the motor network, and the executive control network, while higher disease burden was associated with greater inter-network connectivity between the medial visual network and areas involved in visuomotor learning. Our findings underscore the importance of examining resting-state oscillations in this population, both as a biomarker of disease progression and a potential target for therapeutic intervention.

Increasing age is characterized by greater positive affective states. However, there is mixed evidence on the implementation of emotion regulation strategies across the life span. To clarify the discrepancies in the literature, we examined the modulating influence of contextual factors in understanding emotion regulation strategy use in older and young adults. Forty-eight older adults and forty-nine young adults completed a retrospective survey inquiring about the use of emotion regulation strategies in emotion-eliciting situations experienced over the preceding 2 weeks. We used factor analysis to establish clusters of emotion regulation strategies, resulting in cognitive strategies, acceptance, and maladaptive strategies. Overall, we found context-dependent age-related differences in emotion regulation strategy use. Specifically, older adults reported greater use of acceptance than young adults in situations of moderate intensity and in situations that evoke anxiety and sadness. In addition, older adults reported using maladaptive strategies to a lesser extent in high- and moderate-intensity situations and in situations that elicit anxiety and sadness when compared with young adults. There were no age-related differences in the use of cognitive strategies across contexts. Older adults, compared to young adults, reported less use of maladaptive strategies and greater use of acceptance than young adults, which suggests that the enhanced emotional functioning observed later in life may be due to a shift in strategy implementation. (PsycINFO Database Record

An extensive body of research defines the default-mode network (DMN) to be one of the critical networks of the human brain, playing a pivotal functional role in processes of internal mentation. Alterations in the connectivity of this network as a function of aging have been found, with reductions associated with functional ramifications for the elderly population. This study examined associations between integrity of the DMN and trait levels of mindfulness disposition, defined by our ability to exert attentional and emotional control in the present moment, and, thereby, bring awareness to immediate experiences. Twenty-five older adults participated in the study and underwent a brief functional magnetic resonance imaging session and filled out questionnaires related to their overall health and mindfulness disposition. Mindfulness disposition was associated with greater connectivity of the DMN, specifically, in the dorsal posterior cingulate cortex and the precuneus. Mindfulness disposition, thus, explains variance in the connectivity of one of the more intrinsic networks of the human brain, known to be critical for promoting self-relevant mental explorations and building cognitive and affective control.

Aging is marked by a decline in cognitive function, which is often preceded by losses in gray matter volume. Fortunately, higher cardiorespiratory fitness (CRF) levels are associated with an attenuation of age-related losses in gray matter volume and a reduced risk for cognitive impairment. Despite these links, we have only a rudimentary understanding of whether fitness-related increases in gray matter volume lead to elevated cognitive function. In this cross-sectional study, we examined whether the association between higher aerobic fitness levels and elevated executive function was mediated by greater gray matter volume in the prefrontal cortex (PFC). One hundred and forty-two older adults (mean age = 66.6 years) completed structural magnetic resonance imaging (MRI) scans, CRF assessments, and performed Stroop and spatial working memory (SPWM) tasks. Gray matter volume was assessed using an optimized voxel-based morphometry approach. Consistent with our predictions, higher fitness levels were associated with (a) better performance on both the Stroop and SPWM tasks, and (b) greater gray matter volume in several regions, including the dorsolateral PFC (DLPFC). Volume of the right inferior frontal gyrus and precentral gyrus mediated the relationship between CRF and Stroop interference while a non-overlapping set of regions bilaterally in the DLPFC mediated the association between CRF and SPWM accuracy. These results suggest that specific regions of the DLPFC differentially relate to inhibition and spatial working memory. Thus, fitness may influence cognitive function by reducing brain atrophy in targeted areas in healthy older adults.

Cerebral white matter (WM) degeneration occurs with increasing age and is associated with declining cognitive function. Research has shown that cardiorespiratory fitness and exercise are effective as protective, even restorative, agents against cognitive and neurobiological impairments in older adults. In this study, we investigated whether the beneficial impact of aerobic fitness would extend to WM integrity in the context of a one-year exercise intervention. Further, we examined the pattern of diffusivity changes to better understand the underlying biological mechanisms. Finally, we assessed whether training-induced changes in WM integrity would be associated with improvements in cognitive performance independent of aerobic fitness gains. Results showed that aerobic fitness training did not affect group-level change in WM integrity, executive function, or short-term memory, but that greater aerobic fitness derived from the walking program was associated with greater change in WM integrity in the frontal and temporal lobes, and greater improvement in short-term memory. Increases in WM integrity, however, were not associated with short-term memory improvement, independent of fitness improvements. Therefore, while not all findings are consistent with previous research, we provide novel evidence for correlated change in training-induced aerobic fitness, WM integrity, and cognition among healthy older adults.

We used the Space Fortress videogame, originally developed by cognitive psychologists to study skill acquisition, as a platform to examine learning-induced plasticity of interacting brain networks. Novice videogame players learned Space Fortress using one of two training strategies: (a) focus on all aspects of the game during learning (fixed priority), or (b) focus on improving separate game components in the context of the whole game (variable priority). Participants were scanned during game play using functional magnetic resonance imaging (fMRI), both before and after 20 h of training. As expected, variable priority training enhanced learning, particularly for individuals who initially performed poorly. Functional connectivity analysis revealed changes in brain network interaction reflective of more flexible skill learning and retrieval with variable priority training, compared to procedural learning and skill implementation with fixed priority training. These results provide the first evidence for differences in the interaction of large-scale brain networks when learning with different training strategies. Our approach and findings also provide a foundation for exploring the brain plasticity involved in transfer of trained abilities to novel real-world tasks such as driving, sport, or neurorehabilitation.

Aerobic exercise is a promising form of prevention for cognitive decline; however, little is known about the molecular mechanisms by which exercise and fitness impacts the human brain. Several studies have postulated that increased regional brain volume and function are associated with aerobic fitness because of increased vascularization rather than increased neural tissue per se. We tested this position by examining the relationship between cardiorespiratory fitness and N-acetylaspartate (NAA) levels in the right frontal cortex using magnetic resonance spectroscopy. NAA is a nervous system specific metabolite found predominantly in cell bodies of neurons. We reasoned that if aerobic fitness was predominantly influencing the vasculature of the brain, then NAA levels should not vary as a function of aerobic fitness. However, if aerobic fitness influences the number or viability of neurons, then higher aerobic fitness levels might be associated with greater concentrations of NAA. We examined NAA levels, aerobic fitness, and cognitive performance in 137 older adults without cognitive impairment. Consistent with the latter hypothesis, we found that higher aerobic fitness levels offset an age-related decline in NAA. Furthermore, NAA mediated an association between fitness and backward digit span performance, suggesting that neuronal viability as measured by NAA is important in understanding fitness-related cognitive enhancement. Since NAA is found exclusively in neural tissue, our results indicate that the effect of fitness on the human brain extends beyond vascularization; aerobic fitness is associated with neuronal viability in the frontal cortex of older adults.

The basal ganglia play a central role in regulating the response selection abilities that are critical for mental flexibility. In neocortical areas, higher cardiorespiratory fitness levels are associated with increased gray matter volume, and these volumetric differences mediate enhanced cognitive performance in a variety of tasks. Here we examine whether cardiorespiratory fitness correlates with the volume of the subcortical nuclei that make up the basal ganglia and whether this relationship predicts cognitive flexibility in older adults. Structural MRI was used to determine the volume of the basal ganglia nuclei in a group of older, neurologically healthy individuals (mean age 66 years,N=179). Measures of cardiorespiratory fitness (VO2max), cognitive flexibility (task switching), and attentional control (flanker task) were also collected. Higher fitness levels were correlated with higher accuracy rates in the Task Switching paradigm. In addition, the volume of the caudate nucleus, putamen, and globus pallidus positively correlated with Task Switching accuracy. Nested regression modeling revealed that caudate nucleus volume was a significant mediator of the relationship between cardiorespiratory fitness, and task switching performance. These findings indicate that higher cardiorespiratory fitness predicts better cognitive flexibility in older adults through greater grey matter volume in the dorsal striatum.

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system, resulting in physical, cognitive and affective disturbances, with notable declines in the ability to learn and retain new information. In this study, we examined if higher levels of physical activity in MS individuals were associated with an increased resting-state connectivity of the hippocampus and cortex, resulting in better performance on a task of episodic memory. Forty-five individuals with a clinically definite diagnosis of MS were recruited for the study. Consistent with previous reports, hippocampus was functionally connected to the posteromedial cortex, parahippocampal gyrus, superior frontal gyrus, and the medial frontal cortex. Higher levels of physical activity in MS patients were associated with an increased coherence between the hippocampus and the posteromedial cortex (PMC). The increased connectivity between these two regions, in turn, was predictive of better relational memory, such that MS patients who showed an increased coherence between the left (not right) hippocampus and the PMC also showed better relational memory. Results of the study are interpreted in light of the challenge of disentangling effects of physical activity from effects of disease severity and its neuropathological correlates. (JINS, 2011, 17, 986–997)

Background Self-efficacy and the use of self-regulatory strategies are consistently associated with physical activity behavior. Similarly, behavioral inhibition and cognitive resource allocation—indices of executive control function—have also been associated with this health behavior. Purpose The purpose of this study was to examine the hypothesis that self-efficacy mediates the relationship between self-regulatory processes, such as executive function, and sustained exercise behavior. Methods Older adults (N=177, mean age=66.44 years) completed measures of executive function, self-reported use of self-regulatory strategies, and self-efficacy prior to and during the first month of a 12-month exercise intervention. Percentage of exercise classes attended over the following 11 months was used to represent adherence. Data were collected from 2007 to 2010 and analyzed in 2010–2011. Structural equation models were tested examining the effect of executive function and strategy use on adherence via efficacy. Results As hypothesized, results showed significant direct effects of two elements of executive function and of strategy use on self-efficacy and of efficacy on adherence. In addition, there were significant indirect effects of strategy use and executive function on adherence via self-efficacy. Conclusions Higher levels of executive function and use of self-regulatory strategies at the start of an exercise program enhance beliefs in exercise capabilities, which in turn leads to greater adherence. Trial registration number This study is registered in Clinicaltrials.gov ( NCT 00438347 ).

Alterations in gray and white matter have been well documented in individuals with multiple sclerosis. Severity and extent of such brain tissue damage have been associated with cognitive impairment, disease duration and neurological disability, making quantitative indices of tissue damage important markers of disease progression. In this study, we investigated the association between cardiorespiratory fitness and measures of gray matter atrophy and white matter integrity. Employing voxel-based approaches to analysis of gray matter and white matter, we specifically examined whether higher levels of fitness in multiple sclerosis participants were associated with preserved gray matter volume and integrity of white matter. We found a positive association between cardiorespiratory fitness and regional gray matter volumes and higher focal fractional anisotropy values. Statistical mapping revealed that higher levels of fitness were associated with greater gray matter volume in the midline cortical structures including the medial frontal gyrus, anterior cingulate cortex and the precuneus. Further, we also found that increasing levels of fitness were associated with higher fractional anisotropy in the left thalamic radiation and right anterior corona radiata. Both preserved gray matter volume and white matter tract integrity were associated with better performance on measures of processing speed. Taken together, these results suggest that fitness exerts a prophylactic influence on the structural decline observed early on, preserving neuronal integrity in multiple sclerosis, thereby reducing long-term disability.

Hippocampal volume shrinks in late adulthood, but the neuromolecular factors that trigger hippocampal decay in aging humans remains a matter of speculation. In rodents, brain-derived neurotrophic factor (BDNF) promotes the growth and proliferation of cells in the hippocampus and is important in long-term potentiation and memory formation. In humans, circulating levels of BDNF decline with advancing age, and a genetic polymorphism for BDNF has been related to gray matter volume loss in old age. In this study, we tested whether age-related reductions in serum levels of BDNF would be related to shrinkage of the hippocampus and memory deficits in older adults. Hippocampal volume was acquired by automated segmentation of magnetic resonance images in 142 older adults without dementia. The caudate nucleus was also segmented and examined in relation to levels of serum BDNF. Spatial memory was tested using a paradigm in which memory load was parametrically increased. We found that increasing age was associated with smaller hippocampal volumes, reduced levels of serum BDNF, and poorer memory performance. Lower levels of BDNF were associated with smaller hippocampi and poorer memory, even when controlling for the variation related to age. In an exploratory mediation analysis, hippocampal volume mediated the age-related decline in spatial memory and BDNF mediated the age-related decline in hippocampal volume. Caudate nucleus volume was unrelated to BDNF levels or spatial memory performance. Our results identify serum BDNF as a significant factor related to hippocampal shrinkage and memory decline in late adulthood.

Over the next twenty years the number of Americans diagnosed with dementia is expected to more than double (CDC 2007). It is, therefore, an important public health initiative to understand what factors contribute to the longevity of a healthy mind. Both default mode network (DMN) function and increased aerobic fitness have been associated with better cognitive performance and reduced incidence of Alzheimer’s disease among older adults. Here we examine the association between aerobic fitness, functional connectivity in the DMN, and cognitive performance. Results showed significant age-related deficits in functional connectivity in both local and distributed DMN pathways. However, in a group of healthy elderly adults, almost half of the age-related disconnections showed increased functional connectivity as a function of aerobic fitness level. Finally, we examine the hypothesis that functional connectivity in the DMN is one source of variance in the relationship between aerobic fitness and cognition. Results demonstrate instances of both specific and global DMN connectivity mediating the relationship between fitness and cognition. We provide the first evidence for functional connectivity as a source of variance in the association between aerobic fitness and cognition, and discuss results in the context of neurobiological theories of cognitive aging and disease.

Cognitive difficulties represent a core symptom experienced by individuals with relapsing-remitting multiple sclerosis (RRMS). The field of gerontology has provided evidence that physical activity may moderate the decline in cognitive functioning that occurs with increasing age. Based on that evidence, we examined the association between physical activity and perceived cognitive impairment in people with RRMS. The study sample consisted of 82 individuals with RRMS who completed an initial battery of questionnaires, including the Perceived Deficits Questionnaire (PDQ), wore an accelerometer for 7 days, and then completed the Godin Leisure-Time Exercise Questionnaire (GLTEQ). Physical activity, measured by either an accelerometer or the GLTEQ, was inversely associated with overall PDQ scores, even after controlling for clinical and demographic factors. Additional studies are needed on physical activity as a modifiable behavior with a potential impact on cognitive impairment in individuals with RRMS.

Models of selective attention predict that focused attention to spatially contiguous stimuli may result in enhanced activity in areas of cortex specialized for processing task-relevant and task-irrelevant information. We examined this hypothesis by localizing color-sensitive areas (CSA) and word and letter sensitive areas of cortex and then examining modulation of these regions during performance of a modified version of the Stroop task in which target and distractors are spatially coincident. We report that only the incongruent condition with the highest cognitive demand showed increased activity in CSA relative to other conditions, indicating an attentional enhancement in target processing areas. We also found an enhancement of activity in one region sensitive to word/letter processing during the most cognitively demanding incongruent condition indicating greater processing of the distractor dimension. Correlations with performance revealed that top-down modulation during the task was critical for effective filtering of irrelevant information in conflict conditions. These results support predictions made by models of selective attention and suggest an important mechanism of top-down attentional control in spatially contiguous stimuli.

BACKGROUND AND PURPOSE: T2 hypointensity in the basal ganglia of patients with MS has been associated with clinical progression and cognitive decline. Our objectives were the following: 1) to compare signal in T2WI, R2 (ie, 1/T2), and R2* (ie, 1/T2*) relaxation rates and quantitative susceptibility mapping; and 2) to investigate the associations among MR imaging, clinical scores, and cognitive measures of inhibitory control linked to basal ganglia functioning. MATERIALS AND METHODS: Twenty-nine patients with MS underwent a battery of neuropsychological tests including the Flanker and Stroop tasks. 7T MR imaging included 3D gradient-echo and single-echo multishot spin-echo EPI. Quantitative susceptibility mapping images were calculated by using a Wiener filter deconvolution algorithm. T2WI signal was normalized to CSF. R2 and R2* were calculated by log-linear regression. Average MR imaging metrics for the globus pallidus, putamen, and caudate were computed from manually traced ROIs including the largest central part of each structure. RESULTS: Marked spatial variation was consistently visualized on quantitative susceptibility mapping and T2/T2*WI within each basal ganglia structure. MR imaging metrics correlated with each other for each basal ganglia structure individually. Notably, caudate and putamen quantitative susceptibility mapping metrics were similar, but the putamen R2 was larger than the caudate R2. This finding suggests that tissue features contribute differently to R2 and quantitative susceptibility mapping. Caudate and anterior putamen quantitative susceptibility mapping correlated with the Flanker but not Stroop measures; R2 did not correlate with inhibitory control measures. Putamen quantitative susceptibility mapping and caudate and putamen R2 correlated with the Expanded Disability Status Scale. CONCLUSIONS: Our study showed that quantitative susceptibility mapping and R2 may be complementary indicators for basal ganglia tissue changes in MS. Our findings are consistent with the hypothesis that decreased performance of basal ganglia–reliant tasks involving inhibitory control is associated with increased quantitative susceptibility mapping. BG : basal ganglia EDSS : Expanded Disability Status Scale GP : globus pallidus QSM : quantitative susceptibility mapping R2 : relaxation rate (ie, 1/T2) R2* : relaxation rate (ie, 1/T2*)

Deficits in cognitive abilities are commonly observed among individuals with multiple sclerosis (MS). Recent neuroimaging studies have provided evidence for the existence of cortical plasticity in MS, with cognitively impaired participants recruiting additional brain areas to perform challenging tasks. The existence of altered cerebral activations in MS provides hope for the utilization of neural resources to reduce cognitive deficits that challenge everyday living in MS by employing alternative interventions such as cognitive and fitness training. In this study, we examined whether higher physical fitness levels enhance cognitive and neural plasticity in MS patients. The present study is the first to investigate the impact of cardiorespiratory fitness on cerebrovascular functioning of MS patients. 24 participants with relapsing–remitting MS were recruited for the study. All participants went through a fitness assessment and were scanned in a 3 T MRI system during the Paced Visual Serial Addition Test (PVSAT). Higher fitness levels were associated with faster behavioral performance and greater recruitment of right IFG/MFG, a region of the cerebral cortex recruited by MS patients during performance of PVSAT to purportedly compensate for the cognitive deterioration attributable to MS. In contrast, lower levels of fitness were associated with enhanced ACC activity, suggestive of the presence of greater interference and the potential for error in lower fit MS participants. These results are promising, suggesting the need for further investigation of the utility of aerobic fitness training as a possible method to support the development of additional cortical resources in an attempt to counter the cognitive decline resulting from MS.

Higher cardiorespiratory fitness is associated with better cognitive performance and enhanced brain activation. Yet, the extent to which cardiorespiratory fitness-related brain activation is associated with better cognitive performance is not well understood. In this cross-sectional study, we examined whether the association between cardiorespiratory fitness and executive function was mediated by greater prefrontal cortex activation in healthy older adults. Brain activation was measured during dual-task performance with functional magnetic resonance imaging in a sample of 128 healthy older adults (59-80 years). Higher cardiorespiratory fitness was associated with greater activation during dual-task processing in several brain areas including the anterior cingulate and supplementary motor cortex (ACC/SMA), thalamus and basal ganglia, right motor/somatosensory cortex and middle frontal gyrus, and left somatosensory cortex, controlling for age, sex, education, and gray matter volume. Of these regions, greater ACC/SMA activation mediated the association between cardiorespiratory fitness and dual-task performance. We provide novel evidence that cardiorespiratory fitness may support cognitive performance by facilitating brain activation in a core region critical for executive function.

White matter structure declines with advancing age and has been associated with a decline in memory and executive processes in older adulthood. Yet, recent research suggests that higher physical activity and fitness levels may be associated with less white matter degeneration in late life, although the tract-specificity of this relationship is not well understood. In addition, these prior studies infrequently associate measures of white matter microstructure to cognitive outcomes, so the behavioral importance of higher levels of white matter microstructural organization with greater fitness levels remains a matter of speculation. Here we tested whether cardiorespiratory fitness (VO2max) levels were associated with white matter microstructure and whether this relationship constituted an indirect pathway between cardiorespiratory fitness and spatial working memory in two large, cognitively and neurologically healthy older adult samples. Diffusion tensor imaging was used to determine white matter microstructure in two separate groups: Experiment 1, N=113 (mean age = 66.61) and Experiment 2, N=154 (mean age = 65.66). Using a voxel-based regression approach, we found that higher VO2max was associated with higher fractional anisotropy (FA), a measure of white matter microstructure, in a diverse network of white matter tracts, including the anterior corona radiata, anterior internal capsule, fornix, cingulum, and corpus callosum (pFDR-corrected < .05). This effect was consistent across both samples even after controlling for age, gender, and education. Further, a statistical mediation analysis revealed that white matter microstructure within these regions, among others, constituted a significant indirect path between VO2max and spatial working memory performance. These results suggest that greater aerobic fitness levels are associated with higher levels of white matter microstructural organization, which may, in turn, preserve spatial memory performance in older adulthood.

Multiple sclerosis (MS) is a neurodegenerative disease of the central nervous system that results in diffuse nerve damage and associated physical and cognitive impairments. Of the few comprehensive rehabilitation options that exist for populations with lower baseline cognitive functioning, those that have been successful at eliciting broad cognitive improvements have focused on a multimodal training approach, emphasizing complex cognitive processing that utilizes multiple domains simultaneously.The current study sought to determine the feasibility of an 8-week, hybrid-variable priority training (HVT) program, with a secondary aim to assess the success of this training paradigm at eliciting broad cognitive transfer effects. Capitalizing on the multimodal training modalities offered by the Space Fortress platform, we compared the HVT strategy-based intervention with a waitlist control group, to primarily assess skill acquisition and secondarily determine presence of cognitive transfer. Twenty-eight participants met inclusionary criteria for the study and were randomized to either training or waitlist control groups. To assess broad transfer effects, a battery of neuropsychological tests was administered pre- and post-intervention.The results indicated an overall improvement in skill acquisition and evidence for the feasibility of the intervention, but a lack of broad transfer to tasks of cognitive functioning. Participants in the training group, however, did show improvements on a measure of spatial short-term memory.The current investigation provided support for the feasibility of a multimodal training approach, using the HVT strategy, within the MS population, but lacked broad transfer to multiple domains of cognitive functioning. Future improvements to obtain greater cognitive transfer efficacy would include a larger sample size, a longer course of training to evoke greater game score improvement, the inclusion of only cognitively impaired individuals, and integration of subjective measures of improvement in addition to objective tests of cognitive performance.

Objective Dispositional mindfulness exhibits a positive association with quality of life (QoL). One potential mechanism for this association is enhanced emotion regulation abilities. Individuals with multiple sclerosis (MS) experience a range of physical, cognitive, and affective impairments, thus reducing overall QoL. The current cross-sectional study examines the relation between trait mindfulness and QoL, mediated by emotion dysregulation in individuals with MS. Method Ninety-five participants with self-reported MS completed an online survey that incorporated self-report measures of trait mindfulness, emotion dysregulation, and QoL. Although clinically significant depression was exclusionary, we observed a wide range of depressive symptoms in our sample. These scores were thus entered as a moderator in the mediation analysis. Results Dispositional mindfulness correlated positively with QoL, with lower emotion dysregulation partially mediating the correlation. Depression scores moderated the observed mediation, such that the effect was stronger in those with higher symptoms of depression. Conclusions Trait mindfulness is positively associated with QoL in individuals with MS. Reduced emotion dysregulation may be a critical pathway linking mindfulness and QoL in MS, especially in those with higher symptoms of depression.

Background 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. Methods We examined the relationship between education, a commonly used proxy for cognitive reserve, and N-acetylaspartate (NAA) in neurologically healthy older adults (N = 135; mean age = 66 years). Using single voxel MR spectroscopy, we predicted that higher levels of education would moderate an age-related decline in NAA in the frontal cortex. Results After controlling for the variance associated with cardiorespiratory fitness, sex, annual income, and creatine levels, there were no significant main effects of education (B = 0.016, P = 0.787) or age (B = −0.058, P = 0.204) on NAA levels. However, consistent with our predictions, there was a significant education X age interaction such that more years of education offset an age-related decline in NAA (B = 0.025, P = 0.031). When examining working memory via the backwards digit span task, longer span length was associated with greater education (P

The current study examined how a randomized one-year aerobic exercise program for healthy older adults would affect serum levels of brain-derived neurotrophic factor (BDNF), insulin-like growth factor type 1 (IGF-1), and vascular endothelial growth factor (VEGF) - putative markers of exercise-induced benefits on brain function. The study also examined whether (a) change in the concentration of these growth factors was associated with alterations in functional connectivity following exercise, and (b) the extent to which pre-intervention growth factor levels were associated with training-related changes in functional connectivity. In 65 participants (mean age = 66.4), we found that although there were no group-level changes in growth factors as a function of the intervention, increased temporal lobe connectivity between the bilateral parahippocampus and the bilateral middle temporal gyrus was associated with increased BDNF, IGF-1, and VEGF for an aerobic walking group but not for a non-aerobic control group, and greater pre-intervention VEGF was associated with greater training-related increases in this functional connection. Results are consistent with animal models of exercise and the brain, but are the first to show in humans that exercise-induced increases in temporal lobe functional connectivity are associated with changes in growth factors and may be augmented by greater baseline VEGF.

Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management.

We used functional magnetic resonance imaging (fMRI) to examine brain activity of higher fit and lower fit children during early and late task blocks of a cognitive control flanker paradigm. For congruent trials, all children showed increased recruitment of frontal and parietal regions during the early block when the task was unfamiliar, followed by a decrease in activity in the later block. No within-group changes in congruent accuracy were reported across task blocks, despite a decline in performance across all participants, likely due to fatigue. During incongruent trials, only higher fit children maintained accuracy across blocks, coupled with increased prefrontal and parietal recruitment in the early task block and reduced activity in the later block. Lower fit children showed a decline in incongruent accuracy across blocks, and no changes in activation. We suggest that higher fit children are better at activating and adapting neural processes involved in cognitive control to meet and maintain task goals.

Our recent study reported in PNAS (1) investigated exercise training effects on hippocampal volume, spatial memory, and BDNF in older humans. Our intervention included two training groups: an aerobic walking group and a stretching and toning group. The aerobic group showed increased hippocampal volume and improved memory performance after training. The toning group showed decreased hippocampal volume but also showed improved memory. In their critique, Coen et al. (2) suggest that we overstated the benefits of aerobic training for spatial memory performance, given that the toning group showed enhanced memory performance despite a decrease in hippocampal volume.

The hippocampus shrinks in late adulthood, leading to impaired memory and increased risk for dementia. Hippocampal and medial temporal lobe volumes are larger in higher-fit adults, and physical activity training increases hippocampal perfusion, but the extent to which aerobic exercise training can modify hippocampal volume in late adulthood remains unknown. Here we show, in a randomized controlled trial with 120 older adults, that aerobic exercise training increases the size of the anterior hippocampus, leading to improvements in spatial memory. Exercise training increased hippocampal volume by 2%, effectively reversing age-related loss in volume by 1 to 2 y. We also demonstrate that increased hippocampal volume is associated with greater serum levels of BDNF, a mediator of neurogenesis in the dentate gyrus. Hippocampal volume declined in the control group, but higher preintervention fitness partially attenuated the decline, suggesting that fitness protects against volume loss. Caudate nucleus and thalamus volumes were unaffected by the intervention. These theoretically important findings indicate that aerobic exercise training is effective at reversing hippocampal volume loss in late adulthood, which is accompanied by improved memory function.

The discovery of a coherent set of cortical regions showing activation during rest and deactivation during task performance has reignited an old debate in the field of neuroscience, one that questions the reflexivity of the human brain and provides evidence towards a more intrinsic functional architecture. The default-mode network (DMN) comprising of such consistent cortical regions has become a topic of increasing interest in both healthy and diseased populations. In this study, using a well-examined version of the verbal n-back task, interleaved with periods of rest blocks, we investigated whether the deactivation of the cortical regions comprising the DMN moderates individual differences in behavioral performance in a group of older adults. We recruited 25 young and 25 older adults for our study and presented them with blocks of the n-back task, with varying levels of load, interleaved with periods of fixation. A direct comparison of the young and older participants revealed both a reduction in the up-regulation of the prefrontal and parietal regions in response to increasing task demands, along with a reduction in the down-regulation of DMN regions with increasing cognitive load in the elderly. Better performance in the young adults was associated with the capability to modulate the regions of the working memory network with increasing task difficulty, however enhanced performance in the older cohort was associated with greater load-induced deactivation of the posterior cingulate cortex. This study adds to the existing gamut of aging literature, providing evidence that DMN function is critical to cognitive functioning in older adults.

The present investigation is the first to explore the association between childhood aerobic fitness and basal ganglia structure and function. Rodent research has revealed that exercise influences the striatum by increasing dopamine signaling and angiogenesis. In children, higher aerobic fitness levels are associated with greater hippocampal volumes, superior performance on tasks of attentional and interference control, and elevated event-related brain potential indices of executive function. The present study used magnetic resonance imaging to investigate if higher-fit and lower-fit 9- and 10-year-old children exhibited differential volumes of other subcortical brain regions, specifically the basal ganglia involved in attentional control. The relationship between aerobic fitness, dorsal and ventral striatum volumes and performance on an attention and inhibition Eriksen flanker task was also examined. The results indicated that higher-fit children showed superior flanker task performance compared to lower-fit children. Higher-fit children also showed greater volumes of the dorsal striatum, and dorsal striatum volume was negatively associated with behavioral interference. The results support the claim that the dorsal striatum is involved in cognitive control and response resolution and that these cognitive processes vary as a function of aerobic fitness. No relationship was found between aerobic fitness, the volume of the ventral striatum and flanker performance. The findings suggest that increased childhood aerobic fitness is associated with greater dorsal striatal volumes and that this is related to enhanced cognitive control. Because children are becoming increasingly overweight, unhealthy and unfit, understanding the neurocognitive benefits of an active lifestyle during childhood has important public health and educational implications.

Research has shown the human brain is organized into separable functional networks during rest and varied states of cognition, and that aging is associated with specific network dysfunctions. The present study used functional magnetic resonance imaging (fMRI) to examine low-frequency (.008

Deterioration of the hippocampus occurs in elderly individuals with and without dementia, yet individual variation exists in the degree and rate of hippocampal decay. Determining the factors that influence individual variation in the magnitude and rate of hippocampal decay may help promote lifestyle changes that prevent such deterioration from taking place. Aerobic fitness and exercise are effective at preventing cortical decay and cognitive impairment in older adults and epidemiological studies suggest that physical activity can reduce the risk for developing dementia. However, the relationship between aerobic fitness and hippocampal volume in elderly humans is unknown. In this study, we investigated whether individuals with higher levels of aerobic fitness displayed greater volume of the hippocampus and better spatial memory performance than individuals with lower fitness levels. Furthermore, in exploratory analyses, we assessed whether hippocampal volume mediated the relationship between fitness and spatial memory. Using a region-of-interest analysis on magnetic resonance images in 165 nondemented older adults, we found a triple association such that higher fitness levels were associated with larger left and right hippocampi after controlling for age, sex, and years of education, and larger hippocampi and higher fitness levels were correlated with better spatial memory performance. Furthermore, we demonstrated that hippocampal volume partially mediated the relationship between higher fitness levels and enhanced spatial memory. Our results clearly indicate that higher levels of aerobic fitness are associated with increased hippocampal volume in older humans, which translates to better memory function.

There is debate in the literature regarding the magnitude, nature, and influence of cognitive impairment in individuals with relapsing-remitting multiple sclerosis (RRMS). Therefore, we conducted a meta-analysis that quantified the overall magnitude of cognitive impairment in individuals with RRMS and identified the domains of cognition and clinical/demographic variables that were moderators of the overall effect. We included 57 studies with 3891 participants that yielded a total of 755 effect sizes. Overall, there was a moderate decline in cognitive functioning in individuals with RRMS compared with healthy controls. Larger effects were observed in cognitive domains of motor functioning, mood status and memory and learning. Regarding demographic and clinical variables, age and gender were moderators of cognitive impairment in all cognitive domains, whereas neurological disability and disease duration primarily moderated performance on tasks assessing memory and learning.

We investigated the relative involvement of cortical regions supporting attentional control in older and younger adults during performance on a modified version of the Stroop task. Participants were exposed to two different types of incongruent trials. One of these, an incongruent-ineligible condition, produces conflict at the non-response level, while the second, an incongruent-eligible condition, produces conflict at both non-response and response levels of information processing. Greater attentional control is needed to perform the incongruent-eligible condition compared to other conditions. We examined the cortical recruitment associated with this task in an event-related functional magnetic resonance imaging paradigm in twenty-five older and twenty-five younger adults. Our results indicated that while younger adults demonstrated an increase in the activation of cortical regions responsible for maintaining attentional control in response to increased levels of conflict, such sensitivity and flexibility of the cortical regions to increased attentional control demands was absent in older adults. These results suggest a limitation in older adults’ capabilities for flexibly recruiting the attentional network in response to increasing attentional demands.

Dedifferentiation, or decreased processing specificity, has been suggested to represent a ubiquitous characteristic of cognitive aging. In this study, we examined both age-related differences and intra-group differences in neural specificity in the ventral visual cortex for color, words, faces and places. Our results demonstrated that neural dedifferentiation was not ubiquitous across stimulus categories. Neural dedifferentiation was also relatively stable, across age, in a group of older adults. Older adults with more overall gray matter showed less neural dedifferentiation in the visual cortex. However, regional gray matter volume was not associated with neural dedifferentiation. We illustrate these effects using a discriminability metric, a signal detection theory measure, for neural dedifferentiation that takes into account both magnitude and variance of brain activation. The dedifferentiation measure provides a quantitative means to examine activation patterns and individual difference factors associated with neural dedifferentiation, and to test theories of behavioral dedifferentiation in cognitive aging literature.

Recent studies with multiple sclerosis (MS) participants have provided evidence for cortical reorganization. Greater recruitment of task-related areas and additional brain regions are thought to play an adaptive role in the performance of cognitive tasks. In this study, we compared cortical circuitry recruited by MS patients and controls during a selective attention task that requires both focusing attention on task-relevant information and ignoring or inhibiting task-irrelevant information. Despite comparable behavioral performance, MS patients demonstrated increased neural recruitment of task-related areas along with additional activation of the prefrontal cortices. However, this additional activation was associated with poor behavioral performance, thereby providing evidence against compensatory brain reorganization. Future studies specifically investigating the nature of additional activation seen in MS patients in a wider variety of cognitive tasks would provide insight into the specific cognitive decline in MS.

Previous studies have reported that high concentrations of homocysteine and lower concentrations of vitamins B6, B12, and folate increase the risk for cognitive decline and pathology in aging populations. In this cross-sectional study, high resolution magnetic resonance imaging (MRI) scans and a 3-day food diary were collected on 32 community-dwelling adults between the ages of 59 and 79. We examined the relation between vitamins B6, B12, and folate intake on cortical volume using an optimized voxel-based morphometry (VBM) method and global gray and white matter volume after correcting for age, sex, body mass index, calorie intake, and education. All participants met or surpassed the recommended daily intake for these vitamins. In the VBM analysis, we found that adults with greater vitamin B6 intake had greater gray matter volume along the medial wall, anterior cingulate cortex, medial parietal cortex, middle temporal gyrus, and superior frontal gyrus, whereas people with greater B12 intake had greater volume in the left and right superior parietal sulcus. These effects were driven by vitamin supplementation and were negated when only examining vitamin intake from diet. Folate had no effect on brain volume. Furthermore, there was no relationship between vitamins B6, B12, or folate intake on global brain volume measures, indicating that VBM methods are more sensitive for detecting localized differences in gray matter volume than global measures. These results are discussed in relation to a growing literature on vitamin intake on age-related neurocognitive deterioration.

Background The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition. Methods Fifty-nine healthy but sedentary community-dwelling volunteers, aged 60-79 years, participated in the 6-month randomized clinical trial. Half of the older adults served in the aerobic training group, the other half of the older adults participated in the toning and stretching control group. Twenty young adults served as controls for the magnetic resonance imaging (MRI), and did not participate in the exercise intervention. High spatial resolution estimates of gray and white matter volume, derived from 3D spoiled gradient recalled acquisition MRI images, were collected before and after the 6-month fitness intervention. Estimates of maximal oxygen uptake (VO2) were also obtained. Results Significant increases in brain volume, in both gray and white matter regions, were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning (nonaerobic) control group. As predicted, no significant changes in either gray or white matter volume were detected for our younger participants. Conclusions These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans. Furthermore, these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults.