Semantic processing in older adults is associated with distributed neural activation which varies by association and abstractness of words.

The extent to which the neural systems underlying semantic processes degrade with advanced age remains unresolved, which motivated the current study of neural activation on functional magnetic resonance imaging (fMRI) during semantic judgments of associated vs. unassociated, semantic vs. rhyme, and abstract vs. rhyme word pairs. Thirty-eight older adults, 55-85 years of age, performed semantic association decision tasks in a mixed event-related block fMRI paradigm involving binary judgments as to whether word pairs were related (i.e., semantically associated). As hypothesized, significantly greater activation was evident during processing of associated (vs. unassociated) word pairs in cortical areas implicated in semantic processing, including the angular gyrus, temporal cortex, and inferior frontal cortex. Cortical areas showed greater activation to unassociated (vs. associated) word pairs, primarily within a large occipital cluster. Greater activation was evident in cortical areas when response to semantic vs. phonemic word pairs. Contrasting activation during abstract vs. concrete semantic processing revealed areas of co-activation to both semantic classes, and areas that had greater response to either abstract or concrete word pairs. Neural activation across conditions did not vary as a function of greater age, indicating only minimal age-associated perturbation in neural activation during semantic processing. Therefore, the response of the semantic hubs, semantic control, and secondary association areas appear to be largely preserved with advanced age among older adults exhibiting successful cognitive aging. These findings may provide a useful clinical contrast if compared to activation among adults experiencing cognitive decline due Alzheimer's, frontal-temporal dementia, and other neurodegenerative diseases.

Resting-state network functional connectivity before and after bariatric surgery.

BACKGROUND: Bariatric surgery is an increasingly popular treatment for patients with severe obesity and related health issues (e.g., diabetes, cardiovascular disease). Studies have identified alterations in functional connectivity both in obesity and following surgical treatment for severe obesity. OBJECTIVE: This study aimed to assess brain function via resting-state within-network connectivity in bariatric surgery patients with severe obesity. SETTING: University hospital. METHODS: Thirty-four bariatric surgery patients completed functional neuroimaging at baseline and postoperatively (goal, 12 weeks; actual, 16 weeks, on average). They also self-reported health information. Baseline resting-state functional connectivity (RSFC) was predicted by baseline age, body mass index (BMI), continuous positive airway pressure use, and reported history of rheumatoid arthritis and type 2 diabetes. Change in RSFC was assessed using the same predictors. This model was run with and without controlling for baseline RSFC. RESULTS: Higher baseline BMI predicted lower baseline RSFC in 3 networks. Lower baseline RSFC also was related to rheumatoid arthritis and type 2 diabetes. Difference between baseline and follow-up RSFC was strongly negatively associated with baseline RSFC. Controlling for baseline RSFC, type 2 diabetes negatively predicted RSFC difference. CONCLUSIONS: RSFC may reflect brain dysfunction in patients with obesity and related diseases. That less connectivity at baseline predicted greater positive change suggests that RSFC may be a biomarker of neurocognitive improvement following bariatric surgery. Diseases more prevalent in patients with obesity (e.g., rheumatoid arthritis and type 2 diabetes) along with elevated BMI negatively affect RSFC likely through inflammatory pathways.

Proximal improvement and higher-order resting state network change after multidomain cognitive training intervention in healthy older adults.

Prior randomized control trials have shown that cognitive training interventions resulted in improved proximal task performance, improved functioning of activities of daily living, and reduced dementia risk in healthy older adults. Neural correlates implicated in cognitive training include hub brain regions of higher-order resting state networks including the default mode network, dorsal attention network, frontoparietal control network, and cingulo-opercular network. However, little is known about resting state network change after cognitive training, or the relation between functional brain changes and improvement in proximal task performance. We assessed the 1) change in proximal task performance, 2) change in higher-order resting state network connectivity via functional magnetic resonance imaging, and 3) association between these variables after a multidomain attention/speed-of-processing and working memory randomized control trial in a sample of 58 healthy older adults. Participants in the cognitive training group improved significantly on seven out of eight training tasks immediately after the training intervention with the largest magnitude of improvement in a divided attention/speed-of-processing task, the Double Decision task. Only the frontoparietal control network had significantly strengthened connectivity in the cognitive training group at the post-intervention timepoint. Lastly, higher frontoparietal control network connectivity was associated with improved Double Decision task performance after training in the cognitive training group. These findings show that the frontoparietal control network may strengthen after multidomain cognitive training interventions, and this network may underlie improvements in divided attention/speed-of-processing proximal improvement.

The association between head motion during functional magnetic resonance imaging and executive functioning in older adults.

Minimizing head motion during functional magnetic resonance imaging (fMRI) is important for maintaining the integrity of neuroimaging data. While there are a variety of techniques to control for head motion, oftentimes, individuals with excessive in-scanner motion are removed from analyses. Movement in the scanner tends to increase with age; however, the cognitive profile of these "high-movers" in older adults has yet to be explored. This study aimed to assess the association between in-scanner head motion (i.e., number of "invalid scans" flagged as motion outliers) and cognitive functioning (e.g., executive functioning, processing speed, and verbal memory performance) in a sample of 282 healthy older adults. Spearman's Rank-Order correlations showed that a higher number of invalid scans was significantly associated with poorer performance on tasks of inhibition and cognitive flexibility and with older age. Since performance in these domains tend to decline as a part of the non-pathological aging process, these findings raise concerns regarding the potential systematic exclusion due to motion of older adults with lower executive functioning in neuroimaging samples. Future research should continue to explore prospective motion correction techniques to better ensure the collection of quality neuroimaging data without excluding informative participants from the sample.

Higher-order resting state network association with the useful field of view task in older adults.

Speed-of-processing abilities decline with age yet are important in performing instrumental activities of daily living. The useful field of view, or Double Decision task, assesses speed-of-processing and divided attention. Performance on this task is related to attention, executive functioning, and visual processing abilities in older adults, and poorer performance predicts more motor vehicle accidents in the elderly. Cognitive training in this task reduces risk of dementia. Structural and functional neural correlates of this task suggest that higher-order resting state networks may be associated with performance on the Double Decision task, although this has never been explored. This study aimed to assess the association of within-network connectivity of the default mode network, dorsal attention network, frontoparietal control network, and cingulo-opercular network with Double Decision task performance, and subcomponents of this task in a sample of 267 healthy older adults. Multiple linear regressions showed that connectivity of the cingulo-opercular network is associated with visual speed-of-processing and divided attention subcomponents of the Double Decision task. Cingulo-opercular network and frontoparietal control network connectivity is associated with Double Decision task performance. Stronger connectivity is related to better performance in all cases. These findings confirm the unique role of the cingulo-opercular network in visual attention and sustained divided attention. Frontoparietal control network connectivity, in addition to cingulo-opercular network connectivity, is related to Double Decision task performance, a task implicated in reduced dementia risk. Future research should explore the role these higher-order networks play in reduced dementia risk after cognitive intervention using the Double Decision task.

Cingulo-opercular and frontoparietal control network connectivity and executive functioning in older adults.

Executive function is a cognitive domain that typically declines in non-pathological aging. Two cognitive control networks that are vulnerable to aging-the cingulo-opercular (CON) and fronto-parietal control (FPCN) networks-play a role in various aspects of executive functioning. However, it is unclear how communication within these networks at rest relates to executive function subcomponents in older adults. This study examines the associations between CON and FPCN connectivity and executive function performance in 274 older adults across working memory, inhibition, and set-shifting tasks. Average CON connectivity was associated with better working memory, inhibition, and set-shifting performance, while average FPCN connectivity was associated solely with working memory. CON region of interest analyses revealed significant connections with classical hub regions (i.e., anterior cingulate and anterior insula) for each task, language regions for verbal working memory, right hemisphere dominance for inhibitory control, and widespread network connections for set-shifting. FPCN region of interest analyses revealed largely right hemisphere fronto-parietal connections important for working memory and a few temporal lobe connections for set-shifting. These findings characterize differential brain-behavior relationships between cognitive control networks and executive function in aging. Future research should target these networks for intervention to potentially attenuate executive function decline in older adults.

Circulating Cytokines Predict 1H-Proton MRS Cerebral Metabolites in Healthy Older Adults.

Background: Changes in both circulating cytokines and neurochemical concentrations have been observed in aging. Patterns of change across these factors are associated with age-related pathologies, including neurodegenerative disease. More evidence to define patterns of change that are characteristic of healthy aging is needed, as is an investigation into how age-related changes in blood cytokines and brain neurochemicals may relate to one another in a healthy older adult population. Methods: Single voxel 1H-proton magnetic resonance spectroscopy was collected in medial frontal and medial parietal regions. Phosphocholine and glycerophosphocholine (Cho), myo-inositol (MI), N-acetylaspertate and N-acetylasperglutamate (NAA), creatine and phosphocreatine (Cr), and glutamate and glutamine (Glx) were measured in a sample of 83 healthy, cognitively normal adults aged 52-89. Blood data were collected to quantify 12 cytokines: interleukins (IL-) 2, 5, 6, 7, 8, 10, 12, 13, IL-1 ß, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-17 α. Correlation analyses were performed to assess age relationships between each of these factors. Backward linear regressions were performed. Cytokine data and age were used as predictors of each cerebrospinal fluid (CSF)-corrected metabolite concentration in both voxels. Results: Associations were identified between a variety of cytokines and concentrations of frontal NAA, Cr, and Glx, and of parietal MI, Cho, NAA, and Cr. In the frontal voxel, NAA was predicted by more IL-1B and less TNF-α, Cr by less TNF-α and more IL-5, and Glx by less TNF-α. In the parietal voxel, MI was predicted by more IL-10 and IL-8 and less IL-2, Cho by more TNF-α and less IL-2, NAA by more IL-1B and TNF-α and less IL-13, IL-2, and IL-7, and Cr by more IL-10 and less IL-2. Conclusions: Associations were identified between circulating cytokines and neurometabolite concentrations in this sample of older adults. The present results serve as the initial evidence of relationships between circulating cytokines and neurophysiology. Findings invite further investigation to understand the physiological consequences of aging, and how peripheral inflammatory markers may relate to neurochemical concentrations in healthy aging.

A Systematic Review and Meta-Analysis of Transcranial Direct Current Stimulation to Remediate Age-Related Cognitive Decline in Healthy Older Adults.

BACKGROUND: Transcranial direct current stimulation (tDCS) has been proposed as a possible method for remediating age-associated cognitive decline in the older adult population. While tDCS has shown potential for improving cognitive functions in healthy older adults, stimulation outcomes on various cognitive domains have been mixed. METHODS: A systematic search was performed in four databases: PubMed, EMBASE, Web of Science, and PsychInfo. Search results were then screened for eligibility based on inclusion/exclusion criteria to only include studies where tDCS was applied to improve cognition in healthy older adults 65 years and above. Eligible studies were reviewed and demographic characteristics, tDCS dose parameters, study procedures, and cognitive outcomes were extracted. Reported effect sizes for active compared to sham group in representative cognitive domain were converted to Hedges' g. MAIN RESULTS: A total of thirteen studies involving healthy older adults (n=532, mean age=71.2+5.3 years) were included in the meta-analysis. The majority of included studies (94%) targeted the prefrontal cortex with stimulation intensity 1-2 mA using various electrode placements with anodes near the frontal region. Across all studies, we found Hedges' g values ranged from -0.31 to 1.85 as reported group effect sizes of active stimulation compared to sham. CONCLUSION: While observed outcomes varied, overall findings indicated promising effects of tDCS to remediate cognitive aging and thus deserves further exploration. Future characterization of inter-individual variability in tDCS dose response and applications in larger cohorts are warranted to further validate benefits of tDCS for cognition in healthy older adults.

Cerebral Metabolite Concentrations Are Associated With Cortical and Subcortical Volumes and Cognition in Older Adults.

BACKGROUND: Cerebral metabolites are associated with different physiological processes in brain aging. Cortical and limbic structures play important roles in cognitive aging; however, the relationship between these structures and age remains unclear with respect to physiological underpinnings. Regional differences in metabolite levels may be related to different structural and cognitive changes in aging. METHODS: Magnetic resonance imaging and spectroscopy were obtained from 117 cognitively healthy older adults. Limbic and other key structural volumes were measured. Concentrations of N-acetylaspartate (NAA) and choline-containing compounds (Cho) were measured in frontal and parietal regions. Neuropsychological testing was performed including measures of crystallized and fluid intelligence and memory. RESULTS: NAA in the frontal voxel was associated with limbic and cortical volumes, whereas Cho in parietal cortex was negatively associated with hippocampal and other regional volumes. Hippocampal volume was associated with forgetting, independent of age. Further, parietal Cho and hippocampal volume contributed independent variance to age corrected discrepancy between fluid and crystallized abilities. CONCLUSION: These findings suggest that physiological changes with age in the frontal and parietal cortices may be linked to structural changes in other connected brain regions. These changes are differentially associated with cognitive performance, suggesting potentially divergent mechanisms.

Self-Efficacy Mediates the Association Between Physical Function and Perceived Quality of Life in Individuals with Mild Cognitive Impairment.

BACKGROUND: Research has shown that individuals with mild cognitive impairment (MCI) value quality of life (QoL) above and beyond cognitive function or other potential outcomes in MCI. There is evidence supporting the negative impact of poor physical function on QoL ratings. OBJECTIVE: The study explored whether a modified measure of self-efficacy for managing MCI and education mediated and/or moderated the relationship between physical function and QoL in persons with MCI. METHODS: Baseline data from 200 participants with MCI were obtained from a larger study assessing the effectiveness of a behavioral intervention. Physical function was assessed by the Short Physical Performance Battery. QoL was assessed with the Quality of Life in Alzheimer's Disease scale. Memory-related self-efficacy was assessed using a modified 9-item version of the Chronic Disease Self-Efficacy Scales. Mediation and moderation analyses tested the hypotheses that self-efficacy and education alter the association between physical function and QoL in individuals with MCI. All analyses were adjusted for age, cognitive severity, and sex. RESULTS: Self-efficacy for managing MCI was a significant mediator of the association between physical function and perceived QoL. Individuals with better physical function reported higher self-efficacy which was associated with higher QoL ratings. CONCLUSIONS: Greater self-efficacy for managing MCI mediated the negative association between physical function and quality of life in this exploratory study. Interventions aimed at enhancing memory self-efficacy in MCI may improve perceived QoL, even in the presence of poor physical function. Future research is needed to investigate this further.

Educational Attainment Moderates the Association Between Hippocampal Volumes and Memory Performances in Healthy Older Adults.

Objective: To examine whether educational attainment, as a proxy of cognitive reserve, moderated the association between hippocampal volumes and episodic verbal memory performances in healthy older adults. Methods: Data from 76 community dwelling older adults were included in the present study. Measures of hippocampal volumes (total, left, and right) were obtained using FreeSurfer software. Immediate and delayed verbal recall scores were derived from performances on the California Verbal Learning Test-Second Edition and the Wechsler Memory Scale- Third Edition. Educational attainment was defined by years of education. Linear regression analyses were performed using immediate and delayed recall as dependent variables and hippocampal volumes, years of education, and their interaction terms as independent variables. All analyses were controlled for age, sex, depression, and health status. Results: Total and left Hippocampal volumes had a positive main effect on delayed recall only. Additionally, the interaction between total, left, and right hippocampal volumes and education was a significant predictor for delayed recall performance but not for immediate recall performance. The positive association between hippocampal volumes and delayed recall was greatest in those with more years of education. Conclusion: Larger hippocampal volumes were associated with better delayed verbal recall and the effect on delayed recall was greatest in those with more years of education. Having higher levels of education, or cognitive reserve, may enable individuals to capitalize on greater structural integrity in the hippocampus to support delayed recall in old age. However, longitudinal research is needed to investigate the directionality of these associations.