18 results
Impact of age and apolipoprotein E ε4 status on regional white matter hyperintensity volume and cognition in healthy aging
- Emily J. Van Etten, Pradyumna K. Bharadwaj, Matthew D. Grilli, David A. Raichlen, Georg A. Hishaw, Matthew J. Huentelman, Theodore P. Trouard, Gene E. Alexander
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- Journal:
- Journal of the International Neuropsychological Society , First View
- Published online by Cambridge University Press:
- 22 March 2024, pp. 1-11
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Objective:
White matter hyperintensity (WMH) volume is a neuroimaging marker of lesion load related to small vessel disease that has been associated with cognitive aging and Alzheimer’s disease (AD) risk.
Method:The present study sought to examine whether regional WMH volume mediates the relationship between APOE ε4 status, a strong genetic risk factor for AD, and cognition and if this association is moderated by age group differences within a sample of 187 healthy older adults (APOE ε4 status [carrier/non-carrier] = 56/131).
Results:After we controlled for sex, education, and vascular risk factors, ANCOVA analyses revealed significant age group by APOE ε4 status interactions for right parietal and left temporal WMH volumes. Within the young-old group (50-69 years), ε4 carriers had greater right parietal and left temporal WMH volumes than non-carriers. However, in the old-old group (70-89 years), right parietal and left temporal WMH volumes were comparable across APOE ε4 groups. Further, within ε4 non-carriers, old-old adults had greater right parietal and left temporal WMH volumes than young-old adults, but there were no significant differences across age groups in ε4 carriers. Follow-up moderated mediation analyses revealed that, in the young-old, but not the old-old group, there were significant indirect effects of ε4 status on memory and executive functions through left temporal WMH volume.
Conclusions:These findings suggest that, among healthy young-old adults, increased left temporal WMH volume, in the context of the ε4 allele, may represent an early marker of cognitive aging with the potential to lead to greater risk for AD.
53 2-Back Performance Does Not Differ Between Cognitive Training Groups in Older Adults Without Dementia
- Nicole D Evangelista, Jessica N Kraft, Hanna K Hausman, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Cheshire Hardcastle, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven DeKosky, Georg A Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric Porges, Adam J Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 360-361
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Objective:
Cognitive training is a non-pharmacological intervention aimed at improving cognitive function across a single or multiple domains. Although the underlying mechanisms of cognitive training and transfer effects are not well-characterized, cognitive training has been thought to facilitate neural plasticity to enhance cognitive performance. Indeed, the Scaffolding Theory of Aging and Cognition (STAC) proposes that cognitive training may enhance the ability to engage in compensatory scaffolding to meet task demands and maintain cognitive performance. We therefore evaluated the effects of cognitive training on working memory performance in older adults without dementia. This study will help begin to elucidate non-pharmacological intervention effects on compensatory scaffolding in older adults.
Participants and Methods:48 participants were recruited for a Phase III randomized clinical trial (Augmenting Cognitive Training in Older Adults [ACT]; NIH R01AG054077) conducted at the University of Florida and University of Arizona. Participants across sites were randomly assigned to complete cognitive training (n=25) or an education training control condition (n=23). Cognitive training and the education training control condition were each completed during 60 sessions over 12 weeks for 40 hours total. The education training control condition involved viewing educational videos produced by the National Geographic Channel. Cognitive training was completed using the Posit Science Brain HQ training program, which included 8 cognitive training paradigms targeting attention/processing speed and working memory. All participants also completed demographic questionnaires, cognitive testing, and an fMRI 2-back task at baseline and at 12-weeks following cognitive training.
Results:Repeated measures analysis of covariance (ANCOVA), adjusted for training adherence, transcranial direct current stimulation (tDCS) condition, age, sex, years of education, and Wechsler Test of Adult Reading (WTAR) raw score, revealed a significant 2-back by training group interaction (F[1,40]=6.201, p=.017, η2=.134). Examination of simple main effects revealed baseline differences in 2-back performance (F[1,40]=.568, p=.455, η2=.014). After controlling for baseline performance, training group differences in 2-back performance was no longer statistically significant (F[1,40]=1.382, p=.247, η2=.034).
Conclusions:After adjusting for baseline performance differences, there were no significant training group differences in 2-back performance, suggesting that the randomization was not sufficient to ensure adequate distribution of participants across groups. Results may indicate that cognitive training alone is not sufficient for significant improvement in working memory performance on a near transfer task. Additional improvement may occur with the next phase of this clinical trial, such that tDCS augments the effects of cognitive training and results in enhanced compensatory scaffolding even within this high performing cohort. Limitations of the study include a highly educated sample with higher literacy levels and the small sample size was not powered for transfer effects analysis. Future analyses will include evaluation of the combined intervention effects of a cognitive training and tDCS on nback performance in a larger sample of older adults without dementia.
61 Network Segregation Predicts Processing Speed in the Cognitively Healthy Oldest-old
- Sara A Nolin, Mary E Faulkner, Paul Stewart, Leland Fleming, Stacy Merritt, Roxanne F Rezaei, Pradyumna K Bharadwaj, Mary Kathryn Franchetti, Daniel A Raichlen, Courtney J Jessup, Lloyd Edwards, G Alex Hishaw, Emily J Van Etten, Theodore P Trouard, David S Geldmacher, Virginia G Wadley, Noam Alperin, Eric C Porges, Adam J Woods, Ronald A Cohen, Bonnie E Levin, Tatjana Rundek, Gene E Alexander, Kristina M Visscher
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 367-368
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Objective:
Understanding the factors contributing to optimal cognitive function throughout the aging process is essential to better understand successful cognitive aging. Processing speed is an age sensitive cognitive domain that usually declines early in the aging process; however, this cognitive skill is essential for other cognitive tasks and everyday functioning. Evaluating brain network interactions in cognitively healthy older adults can help us understand how brain characteristics variations affect cognitive functioning. Functional connections among groups of brain areas give insight into the brain’s organization, and the cognitive effects of aging may relate to this large-scale organization. To follow-up on our prior work, we sought to replicate our findings regarding network segregation’s relationship with processing speed. In order to address possible influences of node location or network membership we replicated the analysis across 4 different node sets.
Participants and Methods:Data were acquired as part of a multi-center study of 85+ cognitively normal individuals, the McKnight Brain Aging Registry (MBAR). For this analysis, we included 146 community-dwelling, cognitively unimpaired older adults, ages 85-99, who had undergone structural and BOLD resting state MRI scans and a battery of neuropsychological tests. Exploratory factor analysis identified the processing speed factor of interest. We preprocessed BOLD scans using fmriprep, Ciftify, and XCPEngine algorithms. We used 4 different sets of connectivity-based parcellation: 1)MBAR data used to define nodes and Power (2011) atlas used to determine node network membership, 2) Younger adults data used to define nodes (Chan 2014) and Power (2011) atlas used to determine node network membership, 3) Older adults data from a different study (Han 2018) used to define nodes and Power (2011) atlas used to determine node network membership, and 4) MBAR data used to define nodes and MBAR data based community detection used to determine node network membership.
Segregation (balance of within-network and between-network connections) was measured within the association system and three wellcharacterized networks: Default Mode Network (DMN), Cingulo-Opercular Network (CON), and Fronto-Parietal Network (FPN). Correlation between processing speed and association system and networks was performed for all 4 node sets.
Results:We replicated prior work and found the segregation of both the cortical association system, the segregation of FPN and DMN had a consistent relationship with processing speed across all node sets (association system range of correlations: r=.294 to .342, FPN: r=.254 to .272, DMN: r=.263 to .273). Additionally, compared to parcellations created with older adults, the parcellation created based on younger individuals showed attenuated and less robust findings as those with older adults (association system r=.263, FPN r=.255, DMN r=.263).
Conclusions:This study shows that network segregation of the oldest-old brain is closely linked with processing speed and this relationship is replicable across different node sets created with varied datasets. This work adds to the growing body of knowledge about age-related dedifferentiation by demonstrating replicability and consistency of the finding that as essential cognitive skill, processing speed, is associated with differentiated functional networks even in very old individuals experiencing successful cognitive aging.
2 Higher White Matter Hyperintensity Load Adversely Affects Pre-Post Proximal Cognitive Training Performance in Healthy Older Adults
- Emanuel M Boutzoukas, Andrew O’Shea, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Hanna K Hausman, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Samantha G Smith, Hyun Song, Eric C Porges, Alex Hishaw, Steven T DeKosky, Samuel S Wu, Michael Marsiske, Gene E Alexander, Ronald Cohen, Adam J Woods
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 671-672
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Objective:
Cognitive training has shown promise for improving cognition in older adults. Aging involves a variety of neuroanatomical changes that may affect response to cognitive training. White matter hyperintensities (WMH) are one common age-related brain change, as evidenced by T2-weighted and Fluid Attenuated Inversion Recovery (FLAIR) MRI. WMH are associated with older age, suggestive of cerebral small vessel disease, and reflect decreased white matter integrity. Higher WMH load associates with reduced threshold for clinical expression of cognitive impairment and dementia. The effects of WMH on response to cognitive training interventions are relatively unknown. The current study assessed (a) proximal cognitive training performance following a 3-month randomized control trial and (b) the contribution of baseline whole-brain WMH load, defined as total lesion volume (TLV), on pre-post proximal training change.
Participants and Methods:Sixty-two healthy older adults ages 65-84 completed either adaptive cognitive training (CT; n=31) or educational training control (ET; n=31) interventions. Participants assigned to CT completed 20 hours of attention/processing speed training and 20 hours of working memory training delivered through commercially-available Posit Science BrainHQ. ET participants completed 40 hours of educational videos. All participants also underwent sham or active transcranial direct current stimulation (tDCS) as an adjunctive intervention, although not a variable of interest in the current study. Multimodal MRI scans were acquired during the baseline visit. T1- and T2-weighted FLAIR images were processed using the Lesion Segmentation Tool (LST) for SPM12. The Lesion Prediction Algorithm of LST automatically segmented brain tissue and calculated lesion maps. A lesion threshold of 0.30 was applied to calculate TLV. A log transformation was applied to TLV to normalize the distribution of WMH. Repeated-measures analysis of covariance (RM-ANCOVA) assessed pre/post change in proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures in the CT group compared to their ET counterparts, controlling for age, sex, years of education and tDCS group. Linear regression assessed the effect of TLV on post-intervention proximal composite and sub-composite, controlling for baseline performance, intervention assignment, age, sex, years of education, multisite scanner differences, estimated total intracranial volume, and binarized cardiovascular disease risk.
Results:RM-ANCOVA revealed two-way group*time interactions such that those assigned cognitive training demonstrated greater improvement on proximal composite (Total Training Composite) and sub-composite (Processing Speed Training Composite, Working Memory Training Composite) measures compared to their ET counterparts. Multiple linear regression showed higher baseline TLV associated with lower pre-post change on Processing Speed Training sub-composite (ß = -0.19, p = 0.04) but not other composite measures.
Conclusions:These findings demonstrate the utility of cognitive training for improving postintervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appear to be particularly sensitive to white matter hyperintensity load versus working memory training change. These data suggest that TLV may serve as an important factor for consideration when planning processing speed-based cognitive training interventions for remediation of cognitive decline in older adults.
78 BVMT-R Learning Ratio Moderates Cognitive Training Gains in Useful Field of View Task in Healthy Older Adults
- Cheshire Hardcastle, Jessica N. Kraft, Hanna K. Hausman, Andrew O’Shea, Alejandro Albizu, Nicole D. Evangelista, Emanuel Boutzoukas, Emily J. Van Etten, Pradyumna K. Bharadwaj, Hyun Song, Samantha G. Smith, Eric Porges, Steven DeKosky, Georg A. Hishaw, Samuel Wu, Michael Marsiske, Ronald Cohen, Gene E. Alexander, Adam J. Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 180-181
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Objective:
Cognitive training using a visual speed-of-processing task, called the Useful Field of View (UFOV) task, reduced dementia risk and reduced decline in activities of daily living at a 10-year follow-up in older adults. However, there is variability in the level of cognitive gains after cognitive training across studies. One potential explanation for this variability could be moderating factors. Prior studies suggest variables moderating cognitive training gains share features of the training task. Learning trials of the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) recruit similar cognitive abilities and have overlapping neural correlates with the UFOV task and speed-ofprocessing/working memory tasks and therefore could serve as potential moderators. Exploring moderating factors of cognitive training gains may boost the efficacy of interventions, improve rigor in the cognitive training literature, and eventually help provide tailored treatment recommendations. This study explored the association between the HVLT-R and BVMT-R learning and the UFOV task, and assessed the moderation of HVLT-R and BVMT-R learning on UFOV improvement after a 3-month speed-ofprocessing/attention and working memory cognitive training intervention in cognitively healthy older adults.
Participants and Methods:75 healthy older adults (M age = 71.11, SD = 4.61) were recruited as part of a larger clinical trial through the Universities of Florida and Arizona. Participants were randomized into a cognitive training (n=36) or education control (n=39) group and underwent a 40-hour, 12-week intervention. Cognitive training intervention consisted of practicing 4 attention/speed-of-processing (including the UFOV task) and 4 working memory tasks. Education control intervention consisted of watching 40-minute educational videos. The HVLT-R and BVMT-R were administered at the pre-intervention timepoint as part of a larger neurocognitive battery. The learning ratio was calculated as: trial 3 total - trial 1 total/12 - trial 1 total. UFOV performance was measured at pre- and post-intervention time points via the POSIT Brain HQ Double Decision Assessment. Multiple linear regressions predicted baseline Double Decision performance from HVLT-R and BVMT-R learning ratios controlling for study site, age, sex, and education. A repeated measures moderation analysis assessed the moderation of HVLT-R and BVMT-R learning ratio on Double Decision change from pre- to post-intervention for cognitive training and education control groups.
Results:Baseline Double Decision performance significantly associated with BVMT-R learning ratio (β=-.303, p=.008), but not HVLT-R learning ratio (β=-.142, p=.238). BVMT-R learning ratio moderated gains in Double Decision performance (p<.01); for each unit increase in BVMT-R learning ratio, there was a .6173 unit decrease in training gains. The HVLT-R learning ratio did not moderate gains in Double Decision performance (p>.05). There were no significant moderations in the education control group.
Conclusions:Better visuospatial learning was associated with faster Double Decision performance at baseline. Those with poorer visuospatial learning improved most on the Double Decision task after training, suggesting that healthy older adults who perform below expectations may show the greatest training gains. Future cognitive training research studying visual speed-of-processing interventions should account for differing levels of visuospatial learning at baseline, as this could impact the magnitude of training outcomes.
6 Adjunctive Transcranial Direct Current Stimulation and Cognitive Training Alters Default Mode and Frontoparietal Control Network Connectivity in Older Adults
- Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Emanuel M Boutzoukas, Andrew O’Shea, Alejandro Albizu, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Eric S Porges, Georg A Hishaw, Samuel Wu, Steven DeKosky, Gene E Alexander, Michael Marsiske, Ronald A Cohen, Adam J Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 675-676
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Objective:
Aging is associated with disruptions in functional connectivity within the default mode (DMN), frontoparietal control (FPCN), and cingulo-opercular (CON) resting-state networks. Greater within-network connectivity predicts better cognitive performance in older adults. Therefore, strengthening network connectivity, through targeted intervention strategies, may help prevent age-related cognitive decline or progression to dementia. Small studies have demonstrated synergistic effects of combining transcranial direct current stimulation (tDCS) and cognitive training (CT) on strengthening network connectivity; however, this association has yet to be rigorously tested on a large scale. The current study leverages longitudinal data from the first-ever Phase III clinical trial for tDCS to examine the efficacy of an adjunctive tDCS and CT intervention on modulating network connectivity in older adults.
Participants and Methods:This sample included 209 older adults (mean age = 71.6) from the Augmenting Cognitive Training in Older Adults multisite trial. Participants completed 40 hours of CT over 12 weeks, which included 8 attention, processing speed, and working memory tasks. Participants were randomized into active or sham stimulation groups, and tDCS was administered during CT daily for two weeks then weekly for 10 weeks. For both stimulation groups, two electrodes in saline-soaked 5x7 cm2 sponges were placed at F3 (cathode) and F4 (anode) using the 10-20 measurement system. The active group received 2mA of current for 20 minutes. The sham group received 2mA for 30 seconds, then no current for the remaining 20 minutes.
Participants underwent resting-state fMRI at baseline and post-intervention. CONN toolbox was used to preprocess imaging data and conduct region of interest (ROI-ROI) connectivity analyses. The Artifact Detection Toolbox, using intermediate settings, identified outlier volumes. Two participants were excluded for having greater than 50% of volumes flagged as outliers. ROI-ROI analyses modeled the interaction between tDCS group (active versus sham) and occasion (baseline connectivity versus postintervention connectivity) for the DMN, FPCN, and CON controlling for age, sex, education, site, and adherence.
Results:Compared to sham, the active group demonstrated ROI-ROI increases in functional connectivity within the DMN following intervention (left temporal to right temporal [T(202) = 2.78, pFDR < 0.05] and left temporal to right dorsal medial prefrontal cortex [T(202) = 2.74, pFDR < 0.05]. In contrast, compared to sham, the active group demonstrated ROI-ROI decreases in functional connectivity within the FPCN following intervention (left dorsal prefrontal cortex to left temporal [T(202) = -2.96, pFDR < 0.05] and left dorsal prefrontal cortex to left lateral prefrontal cortex [T(202) = -2.77, pFDR < 0.05]). There were no significant interactions detected for CON regions.
Conclusions:These findings (a) demonstrate the feasibility of modulating network connectivity using tDCS and CT and (b) provide important information regarding the pattern of connectivity changes occurring at these intervention parameters in older adults. Importantly, the active stimulation group showed increases in connectivity within the DMN (a network particularly vulnerable to aging and implicated in Alzheimer’s disease) but decreases in connectivity between left frontal and temporal FPCN regions. Future analyses from this trial will evaluate the association between these changes in connectivity and cognitive performance post-intervention and at a one-year timepoint.
28 Factor Structure of Conventional Neuropsychological Tests and NIH-Toolbox in Healthy Older Adults
- Kailey Langer, Cheshire Hardcastle, Hanna Hausman, Jessica Kraft, Alejandro Albizu, Nicole Evangelista, Emanuel Boutzoukas, Andrew O’Shea, Emily Van Etten, Samantha Smith, Hyun Song, Pradyumna Bharadwaj, Georg Hishaw, Samuel Wu, Steven DeKosky, Gene Alexander, Eric Porges, Michael Marsiske, Ronald Cohen, Adam Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, p. 710
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The National Institutes of Health-Toolbox cognition battery (NIH-TCB) is widely used in cognitive aging studies and includes measures in cognitive domains evaluated for dimensional structure and psychometric properties in prior research. The present study addresses a current literature gap by demonstrating how NIH-TCB integrates into a battery of traditional clinical neuropsychological measures. The dimensional structure of NIH-TCB measures along with conventional neuropsychological tests is assessed in healthy older adults.
Participants and Methods:Baseline cognitive data were obtained from 327 older adults. The following measures were collected: NIH-Toolbox cognitive battery, Controlled Oral Word Association (COWA) letter and animals tests, Wechsler Test of Adult Reading (WTAR), Stroop Color-Word Interference Test, Paced Auditory Serial Addition Test (PASAT), Brief Visuospatial Memory Test (BVMT), Letter-Number Sequencing (LNS), Hopkins Verbal Learning Test (HVLT), Trail Making Test A&B, Digit Span. Hmisc, psych, and GPARotation packages for R were used to conduct exploratory factor analyses (EFA). A 5-factor solution was conducted followed by a 6-factor solution. Promax rotation was used for both EFA models.
Results:The 6-factor EFA solution is reported here. Results indicated the following 6 factors: working memory (Digit Span forward, backward, and sequencing, PASAT trials 1 and 2, NIH-Toolbox List Sorting, LNS), speed/executive function (Stroop color naming, word reading, and color-word interference, NIH-Toolbox Flanker, Dimensional Change, and Pattern Comparison, Trail Making Test A&B), verbal fluency (COWA letters F-A-S), crystallized intelligence (WTAR, NIH-Toolbox Oral Recognition and Picture Vocabulary), visual memory (BVMT immediate and delayed), and verbal memory (HVLT immediate and delayed. COWA animals and NIH-Toolbox Picture Sequencing did not adequately load onto any EFA factor and were excluded from the subsequent CFA.
Conclusions:Findings indicate that in a sample of healthy older adults, these collected measures and those obtained through the NIH-Toolbox battery represent 6 domains of cognitive function. Results suggest that in this sample, picture sequencing and COWA animals did not load adequately onto the factors created from the rest of the measures collected. These findings should assist in interpreting future research using combined NIH-TCB and neuropsychological batteries to assess cognition in healthy older adults.
3 Associations Between Exercise Type, Fluid Intelligence, and Processing Speed in the Oldest-Old
- Brian Ho, Joseph Gullett, Stephen Anton, Gene Alexander, Cortney Jessup, Bonnie Levin, Tatjana Rundek, Kristina Visscher, Adam Woods, Ronald Cohen
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 672-673
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Exercise elicits a variety of physiological responses in the body. In the brain, exercise can modulate levels of neurotransmitters and other neurochemicals as well as sparking neurogenesis and structural changes. Downstream psychological effects of exercise include changes in mood and cognition. These changes vary depending on the type of exercise conducted (e.g., running versus strength training). While much is known about the effects of exercise in animals and adult humans, literature on the oldest-old (>= 85 years old) is sparse. The present cross-sectional study explores the relationship between exercise and cognition in the oldest-old.
Participants and Methods:The final sample includes 194 cognitively healthy participants (106 females, MoCA mean score = 24.75) aged 85 to 99 years old (mean = 88.48). Each participant completed the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire and a cognitive battery comprising of the NIH Toolbox, digit coding, symbol search, verbal fluency, and Stroop task. Three groups (sedentary, cardio, and cardio plus strength training) were derived from responses on CHAMPS.
Results:The cardio plus strength training group performed significantly better on the cognitive measures compared to the sedentary group. For two measures, digit coding and symbol search, the cardio plus strength training group also performed significantly better than the cardio group. Cardio group did not significantly differ from the sedentary group on the cognitive measures. All at p < 0.05 and adjusted for multiple comparisons.
Conclusions:Our findings suggest exercise in the oldest-old is linked with higher fluid intelligence and better performance on cognitive measures of processing speed and that there may be an additive effect of exercise types on cognition.
9 Connecting memory and functional brain networks in older adults: a resting state fMRI study
- Jori L Waner, Hanna K Hausman, Jessica N Kraft, Cheshire Hardcastle, Nicole D Evangelista, Andrew O’Shea, Alejandro Albizu, Emanuel M Boutzoukas, Emily J Van Etten, Pradyumna K Bharadwaj, Hyun Song, Samantha G Smith, Steven T DeKosky, Georg A Hishaw, Samuel S Wu, Michael Marsiske, Ronald Cohen, Gene E Alexander, Eric C Porges, Adam J Woods
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 527-528
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Nonpathological aging has been linked to decline in both verbal and visuospatial memory abilities in older adults. Disruptions in resting-state functional connectivity within well-characterized, higherorder cognitive brain networks have also been coupled with poorer memory functioning in healthy older adults and in older adults with dementia. However, there is a paucity of research on the association between higherorder functional connectivity and verbal and visuospatial memory performance in the older adult population. The current study examines the association between resting-state functional connectivity within the cingulo-opercular network (CON), frontoparietal control network (FPCN), and default mode network (DMN) and verbal and visuospatial learning and memory in a large sample of healthy older adults. We hypothesized that greater within-network CON and FPCN functional connectivity would be associated with better immediate verbal and visuospatial memory recall. Additionally, we predicted that within-network DMN functional connectivity would be associated with improvements in delayed verbal and visuospatial memory recall. This study helps to glean insight into whether within-network CON, FPCN, or DMN functional connectivity is associated with verbal and visuospatial memory abilities in later life.
Participants and Methods:330 healthy older adults between 65 and 89 years old (mean age = 71.6 ± 5.2) were recruited at the University of Florida (n = 222) and the University of Arizona (n = 108). Participants underwent resting-state fMRI and completed verbal memory (Hopkins Verbal Learning Test - Revised [HVLT-R]) and visuospatial memory (Brief Visuospatial Memory Test - Revised [BVMT-R]) measures. Immediate (total) and delayed recall scores on the HVLT-R and BVMT-R were calculated using each test manual’s scoring criteria. Learning ratios on the HVLT-R and BVMT-R were quantified by dividing the number of stimuli (verbal or visuospatial) learned between the first and third trials by the number of stimuli not recalled after the first learning trial. CONN Toolbox was used to extract average within-network connectivity values for CON, FPCN, and DMN. Hierarchical regressions were conducted, controlling for sex, race, ethnicity, years of education, number of invalid scans, and scanner site.
Results:Greater CON connectivity was significantly associated with better HVLT-R immediate (total) recall (ß = 0.16, p = 0.01), HVLT-R learning ratio (ß = 0.16, p = 0.01), BVMT-R immediate (total) recall (ß = 0.14, p = 0.02), and BVMT-R delayed recall performance (ß = 0.15, p = 0.01). Greater FPCN connectivity was associated with better BVMT-R learning ratio (ß = 0.13, p = 0.04). HVLT-R delayed recall performance was not associated with connectivity in any network, and DMN connectivity was not significantly related to any measure.
Conclusions:Connectivity within CON demonstrated a robust relationship with different components of memory function as well across verbal and visuospatial domains. In contrast, FPCN only evidenced a relationship with visuospatial learning, and DMN was not significantly associated with memory measures. These data suggest that CON may be a valuable target in longitudinal studies of age-related memory changes, but also a possible target in future non-invasive interventions to attenuate memory decline in older adults.
18 Regional patterns of mitochondrial function using phosphorus magnetic resonance spectroscopy in older adults at-risk for Alzheimer’s disease.
- Francesca V Lopez, Andrew O’Shea, Stacey Alvarez-Alvarado, Adrianna Ratajska, Lauren Kenney, Rachel Schade, Katie Rodriguez, Alyssa Ray, Rebecca O’Connell, Lauren Santos, Emily Van Etten, Hyun Song, Emma Armstrong, Tiffany Gin, Zhiguang Huo, Gene Alexander, Adam J Woods, Dawn Bowers
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- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 331-332
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The brain is reliant on mitochondria to carry out a host of vital cellular functions (e.g., energy metabolism, respiration, apoptosis) to maintain neuronal integrity. Clinically relevant, dysfunctional mitochondria have been implicated as central to the pathogenesis of Alzheimer’s disease (AD). Phosphorous magnetic resonance spectroscopy (31p MRS) is a non-invasive and powerful method for examining in vivo mitochondrial function via high energy phosphates and phospholipid metabolism ratios. At least one prior 31p MRS study found temporal-frontal differences for high energy phosphates in persons with mild AD. The goal of the current study was to examine regional (i.e., frontal, temporal) 31p MRS ratios of mitochondrial function in a sample of older adults at-risk for AD. Given the high energy consumption in temporal lobes (i.e., hippocampus) and preferential age-related changes in frontal structure-function, we predicted 31p MRS ratios of mitochondrial function would be greater in temporal as compared to frontal regions.
Participants and Methods:The current study leveraged baseline neuroimaging data from an ongoing multisite study at the University of Florida and University of Arizona. Participants were older adults with memory complaints and a first-degree family history of AD [N = 70; mean [M] age [years] = 70.9, standard deviation [SD] =5.1; M education [years] = 16.2, SD = 2.2; M MoCA = 26.5, SD = 2.4; 61.4% female; 91.5% non-latinx white]. To achieve optimal sensitivity, we used a single voxel method to examine 31p MRS ratios (bilateral prefrontal and left temporal). Mitochondrial function was estimated by computing 5 ratios for each voxel: summed adenosine triphosphate to total pooled phosphorous (ATP/TP; momentary energy), ATP to inorganic phosphate (ATP/Pi; energy consumption), phosphocreatine to ATP (PCr/ATP; energy reserve), phosphocreatine to inorganic phosphate (PCr/Pi; oxidative phosphorylation), and phosphomonoesters to phosphodiesters (PME/PDE; cellular membrane turnover rate). All ratios were corrected for voxel size and cerebrospinal fluid fraction. Separate repeated measures analyses of variance controlling for scanner site differences (RM ANCOVAs) were performed.
Results:31p MRS ratios were unrelated to demographic characteristics and were not included as additional covariates in analyses. Results of separate RM ANCOVAs revealed all 31p MRS ratios of mitochondrial function were greater in left temporal relative to bilateral prefrontal voxel: ATP/TP (p < .001), ATP/Pi (p = .001), PCr/ATP (p = .004), PCr/Pi (p = .004), and PME/PDE (p = .017). Effect sizes (partial eta squared) ranged from 0.6-.20.
Conclusions:Consistent and extending one prior study, all 31p MRS ratios of mitochondrial function were greater in temporal as compared to frontal regions in older adults at-risk for AD. This may in part be related to the intrinsically high metabolic rate of the temporal region and preferential age-related changes in frontal structure-function. Alternatively, findings may reflect the influence of unaccounted factors (e.g., hemodynamics, auditory stimulation). Longitudinal study designs may inform whether patterns of mitochondrial function across different brain regions are present early in development, occur across the lifespan, or some combination. In turn, this may inform future studies examining differences in mitochondrial function (as measured using 31p MRS) in AD.
Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample
- Sara A. Nolin, Hannah Cowart, Stacy Merritt, Katalina McInerney, P. K. Bharadwaj, Mary Kate Franchetti, David A. Raichlen, Cortney J. Jessup, G. Alex Hishaw, Emily J. Van Etten, Theodore P. Trouard, David S. Geldmacher, Virginia G. Wadley, Eric S. Porges, Adam J. Woods, Ron A. Cohen, Bonnie E. Levin, Tatjana Rundek, Gene E. Alexander, Kristina M. Visscher
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue 6 / July 2023
- Published online by Cambridge University Press:
- 14 October 2022, pp. 605-614
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Objective:
To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old).
Method:Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores.
Results:Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores.
Conclusion:The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use’s impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.
Radiation and electron thermal conduction damping of acoustic perturbations in igniting deuterium–tritium gas
- Conner D. Galloway, Robert O. Hunter, Jr, Alexander V. Valys, Gene H. McCall
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- Journal of Plasma Physics / Volume 85 / Issue 6 / December 2019
- Published online by Cambridge University Press:
- 14 November 2019, 905850606
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We derive a dispersion relation for the damping of acoustic waves in equi-molar deuterium–tritium (DT) gas due to radiation coupling and electron thermal conduction and discuss its significance for inertial confinement fusion (ICF) targets with high-Z shells surrounding a central DT fuel region. As the shell implodes around DT fuel in such a target, shocks and waves are transmitted through the DT gas. If the shell is perturbed due to drive non-uniformity or manufacturing imperfection, these shocks and waves may be perturbed as well, and can potentially re-perturb the shell. This can complicate calculation of shell stability and implosion asymmetry and in general make the target less robust against implosion non-uniformity. Damping of perturbations in DT gas can alleviate these complications. Also, damping of low-order modes, which is primarily due to radiation coupling, can drive the DT gas to an isobaric and isothermal ‘equilibrium’ configuration during ignition. We find that for the range of common ignition temperatures in targets with high-Z shells, $2.5\lesssim T_{ig}\lesssim 3.5$ keV, damping of low-order modes is significant for areal densities ($\unicode[STIX]{x1D70C}r$) in the broad range of $0.6\lesssim \unicode[STIX]{x1D70C}r\lesssim 1.8~\text{g}~\text{cm}^{-2}$. This suggests it is advantageous to design these targets to achieve areal densities at ignition within this range. Furthermore, we derive a simple constraint between areal density and temperature, $\unicode[STIX]{x1D70C}r=0.34T_{o}$ where $T_{o}$ is in keV, such that DT gas undergoing equilibrium ignition is optimally robust against non-uniformity.
Resonance Raman Spectroscopy to Study and Characterize Defects on Carbon Nanotubes and other Nano-Graphite Systems
- Ado Jorio, Luiz Gustavo Cançado, Bernardo R. A. Neves, Mauricio de Souza, Cristiano Fantini, Marcos A. Pimenta, G. Medeiros-Ribeiro, Georgii G. Samsonidze, Shin Grace Chou, Gene Dresselhaus, Mildred S. Dresselhaus, A. M. Rao, Alexander Grüneis, Riichiro Saito
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- Journal:
- MRS Online Proceedings Library Archive / Volume 858 / 2004
- Published online by Cambridge University Press:
- 01 February 2011, HH11.2
- Print publication:
- 2004
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The use of resonance Raman spectroscopy (RRS) to study and characterize single wall carbon nanotubes (SWNTs) is discussed, focusing on preliminary efforts for the development of the RRS to characterize defects in SWNTs. The disorder-induced D-band, disorder-induced peaks just above the first-order allowed graphite G-band, as well as the intermediate frequency modes (IFMs) appearing between the RBM and the D/G spectral region are addressed. RRS on nanographite ribbons and on a step-like defect in highly ordered pyrolytic graphite (HOPG) sheds light into the problem of characterizing specific defects in nano-related carbons.
Corrections to the Optical Transition Energies in Single-Wall Carbon Nanotubes of Smaller Diameters
- Georgii G. Samsonidze, Riichiro Saito, Jie Jiang, Alexander Grüneis, Naoki Kobayashi, Ado Jorio, Shin G. Chou, Gene Dresselhaus, Mildred S. Dresselhaus
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- Journal:
- MRS Online Proceedings Library Archive / Volume 858 / 2004
- Published online by Cambridge University Press:
- 01 February 2011, HH7.2
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- 2004
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Optical spectroscopy characterization of carbon nanotube samples requires accurate determination of their band structure and exciton binding energies. In this paper, we present a non-orthogonal density-functional based tight-binding calculation for the electronic transition energies in single-wall carbon nanotubes. We show that the curvature-induced rehybridization of the electronic orbitals, long-range atomic interactions, and geometrical structure relaxation all have a significant impact on the electronic transition energies in the small diameter limit. After including quasiparticle corrections and exciton binding energies, the calculated electronic transition energies show good agreement with the experimental transition energies observed by photoluminescence and resonance Raman spectroscopy.
Characterization of nanographite and carbon nanotubes by polarization dependent optical spectroscopy
- Alexander Grüneis, Riichiro Saito, Georgii G. Samsonidze, Marcos A. Pimenta, Ado Jorio, Antonio G. Souza Filho, Gene Dresselhaus, Mildred S. Dresselhaus
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- Journal:
- MRS Online Proceedings Library Archive / Volume 737 / 2002
- Published online by Cambridge University Press:
- 11 February 2011, F3.47
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- 2002
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The optical absorption for ? electrons as a function of the electron wavevector k is investigated by first order perturbation theory in graphite and single wall carbon nanotubes (SWNTs). The matrix element connecting two states in the valence and conduction bands is found to be significantly anisotropic in k-space and polarization dependent. In the case of graphite, the absorption shows a node around the equi-energy contour, and in the case of SWNTs we obtain selection rules that allow only transitions between certain pairs of subbands. The strength of the optical absorption is not only diameter dependent but also chirality dependent. The implications of the optical absorption matrix element on the resonant conditions are discussed.
Anisotropy in the Phonon Dispersion Relations of Graphite and Carbon Nanotubes Measured by Raman Spectroscopy
- Georgii G. Samsonidze, Riichiro Saito, Ado Jorio, Antonio G. Souza Filho, Alexander Grüneis, Marcos A. Pimenta, Gene Dresselhaus, Mildred S. Dresselhaus
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- Journal:
- MRS Online Proceedings Library Archive / Volume 737 / 2002
- Published online by Cambridge University Press:
- 11 February 2011, F8.10
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- 2002
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The possible semiconducting device use of single wall carbon nanotubes (SWNTs) requires a technique for the determination of the exact structure of the nanotubes assembled in the device configuration. Raman spectroscopy has been established as a precise and non-destructive tool for the characterization of graphitic nanostructures. Double resonance theory, which is used to explain the dispersive nature of the Raman bands, has attracted much attention for its potential use for the characterization of the electronic and phonon spectra of these nanostructures. Dispersive features in the Raman spectra of low dimensional graphitic materials, such as carbon nanotubes, can be used to measure directly the anisotropy, or the trigonal warping effect, in the phonon dispersion relations about the hexagonal corner of the Brillouin zone (BZ) of graphite.
Thermoelectric Properties of PbSe Epitaxial Thin Films and PbSe/EuS Heterostructures
- Mildred S. Dresselhaus, Gene Dresselhaus, Elena I. Rogacheva, Tatyana V. Tavrina, Sergey N. Grigorov, Konstantin A. Nasedkin, Valentine V. Volobuev, Alexander Yu. Sipatov
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- Journal:
- MRS Online Proceedings Library Archive / Volume 691 / 2001
- Published online by Cambridge University Press:
- 21 March 2011, G8.18
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- 2001
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Systematic investigations were performed of the thickness dependences of the thermoelectric properties of PbSe thin films, freshly prepared and exposed to air at room temperature. It is shown that oxidation leads to a sharp change in the thermoelectric properties of the PbSe films including a change in the sign of the dominant carrier type from n-type to p- type at d ≤ 80 nm. Using a two carrier model for thin films (d < 50 nm) and a two-layer model for thick films (d > 50 nm) allows us to give a satisfactory qualitative interpretation of the observed experimental dependences of the thermoelectric properties on the film thickness.
PET reveals occipitotemporal pathway activation during elementary form perception in humans
- LORI L. BEASON-HELD, KEITH P. PURPURA, JOHN W. VAN METER, NINA P. AZARI, DAVID J. MANGOT, LANCE M. OPTICAN, MARC J. MENTIS, GENE E. ALEXANDER, CHERYL L. GRADY, BARRY HORWITZ, STANLEY I. RAPOPORT, MARK B. SCHAPIRO
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- Journal:
- Visual Neuroscience / Volume 15 / Issue 3 / March 1998
- Published online by Cambridge University Press:
- 01 March 1998, pp. 503-510
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To define brain regions involved in feature extraction or elementary form perception, regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) in subjects viewing two classes of achromatic textures. Textures composed of local features (e.g. extended contours and rectangular blocks) produced activation or increased rCBF along the occipitotemporal pathway relative to textures with the same mean luminance, contrast, and spatial-frequency content but lacking organized form elements or local features. Significant activation was observed in striate, extrastriate, lingual, and fusiform cortices as well as the hippocampus and brain stem. On a scan-by-scan basis, increases in rCBF shifted from the occipitotemporal visual cortices to medial temporal (hippocampus) and frontal lobes with increased exposure to only those textures containing local features. These results suggest that local feature extraction occurs throughout the occipitotemporal (ventral) pathway during extended exposure to visually salient stimuli, and may indicate the presence of similar receptive-field mechanisms in both occipital and temporal visual areas of the human brain.