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Aging is a public health concern with an ever-increasing magnitude worldwide. An array of neuroscience-based approaches like transcranial direct current stimulation (tDCS) and cognitive training have garnered attention in the last decades to ameliorate the effects of cognitive aging in older adults. This study evaluated the effects of 3 months of bilateral tDCS over the frontal cortices with multimodal cognitive training on working memory capacity. Two hundred ninety-two older adults without dementia were allocated to active or sham tDCS paired with cognitive training. These participants received repeated sessions of bilateral tDCS over the bilateral frontal cortices, combined with multimodal cognitive training. Working memory capacity was assessed with the digit span forward, backward, and sequencing tests. No baseline differences between active and sham groups were observed. Multiple linear regressions indicated more improvement of the longest digit span backward from baseline to post-intervention (p = 0.021) and a trend towards greater improvement (p = 0.056) of the longest digit span backward from baseline to 1 year in the active tDCS group. No significant between-group changes were observed for digit span forward or digit span sequencing. The present results provide evidence for the potential for tDCS paired with cognitive training to remediate age-related declines in working memory capacity. These findings are sourced from secondary outcomes in a large randomized clinical trial and thus deserve future targeted investigation in older adult populations., (© 2024. The Author(s), under exclusive licence to American Aging Association.)

Pharmacological interventions for depression and anxiety in older adults often have significant side effects, presenting the need for more tolerable alternatives. Transcranial direct current stimulation (tDCS) is a promising non-pharmacological intervention for depression in clinical populations. However, its effects on depression and anxiety symptoms, particularly in older adults from the general public, are understudied. We conducted a secondary analysis of the Augmenting Cognitive Training in Older Adults (ACT) trial to assess tDCS efficacy in reducing psychological symptoms in older adults. We hypothesized that active stimulation would yield greater reductions in depression and state anxiety compared to sham post-intervention and at the one-year follow-up. We also explored tDCS effects in subgroups characterized by baseline symptom severity. A sample of 378 older adults recruited from the community completed a 12-week tDCS intervention with cognitive or education training. Electrodes were placed at F3/F4, and participants received active or sham tDCS during training sessions. We assessed the association between tDCS group and changes in depression, state anxiety, and trait anxiety from baseline to post-intervention and one-year controlling for covariates. The active tDCS group demonstrated greater reductions in depression and state anxiety compared to sham post-intervention, particularly in individuals with mild depression and moderate/severe state anxiety at baseline. Furthermore, the active tDCS group with moderate/severe state anxiety maintained greater symptom reductions at one-year. tDCS effectively reduced depression and state anxiety symptoms in a large sample of older adults. These findings highlight the importance of considering symptom severity when identifying those who may benefit most from this intervention. • Active tDCS yielded greater reductions in depression and state anxiety than sham. • These reductions were largest for those with mild depression and moderate/severe state anxiety. • tDCS effects on state anxiety remained at one-year for those with moderate/severe state anxiety. • There were no significant tDCS effects on trait anxiety. • tDCS effectively reduces psychological symptoms in a community sample of older adults. [ABSTRACT FROM AUTHOR]

There is a need for effective interventions to stave off cognitive decline in older adults. Cognitive training has variably produced gains in untrained tasks and daily functioning. Combining cognitive training with transcranial direct current stimulation (tDCS) may augment cognitive training effects; however, this approach has yet to be tested on a large-scale. This paper will present the primary findings of the Augmenting Cognitive Training in Older Adults (ACT) clinical trial. We hypothesize that receiving active stimulation with cognitive training will result in greater improvements on an untrained fluid cognition composite compared to sham following intervention. 379 older adults were randomized, and 334 were included in intent-to-treat analyses for a 12-week multidomain cognitive training and tDCS intervention. Active or sham tDCS was administered at F3/F4 during cognitive training daily for two weeks then weekly for 10 weeks. To assess the tDCS effect, we fitted regression models for changes in NIH Toolbox Fluid Cognition Composite scores immediately following intervention and one year from baseline controlling for covariates and baseline scores. Across the entire sample, there were improvements in NIH Toolbox Fluid Cognition Composite scores immediately post-intervention and one year following baseline; however, there were no significant tDCS group effects at either timepoint. The ACT study models rigorous, safe administration of a combined tDCS and cognitive training intervention in a large sample of older adults. Despite potential evidence of near-transfer effects, we failed to demonstrate an additive benefit of active stimulation. Future analyses will continue to assess the intervention's efficacy by examining additional measures of cognition, functioning, mood, and neural markers. • Post-tDCS and cognitive training, the sample improved on an untrained fluid cognition composite. • Improvements on the untrained fluid cognition composite maintained one year following baseline. • In the overall sample, there were no significant tDCS effects on changes in cognitive performance. • It is feasible to administer tDCS and cognitive training safely in older adults on a large scale. • Using individualized tDCS dosing parameters may better facilitate a treatment response. [ABSTRACT FROM AUTHOR]

Objective: This study examines the impact of transcranial direct current stimulation (tDCS) combined with cognitive training on neurotransmitter concentrations in the prefrontal cortex. Materials and Methods: Twenty-three older adults were randomized to either active-tDCS or sham-tDCS in combination with cognitive training for 2 weeks. Active-tDCS was delivered over F3 (cathode) and F4 (anode) electrode placements for 20 min at 2 mA intensity. For each training session, 40-min of computerized cognitive training were applied with active or sham stimulation delivered during the first 20-min. Glutamine/glutamate (Glx) and gamma-aminobutyric acid (GABA) concentrations via proton magnetic resonance spectroscopy were evaluated at baseline and at the end of 2-week intervention. Results: Glx concentrations increased from pre- to post-intervention (p = 0.010) in the active versus sham group after controlling for age, number of intervention days, MoCA scores, and baseline Glx concentration. No difference in GABA concentration was detected between active and sham groups (p = 0.650) after 2-week intervention. Conclusion: Results provide preliminary evidence suggesting that combining cognitive training and tDCS over the prefrontal cortex elicits sustained increase in excitatory neurotransmitter concentrations. Findings support the combination of tDCS and cognitive training as a potential method for altering neurotransmitter concentrations in the frontal cortices, which may have implications for neuroplasticity in the aging brain. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Subthreshold depressive symptoms are both prevalent and associated with negative outcomes in older adults, including conversion to major depressive disorder and other medical conditions. Antidepressants are not recommended as first-line or sole intervention for subthreshold depression; thus, finding other efficacious interventions is important. In depressed adults, transcranial direct current stimulation (tDCS) applied to the frontal lobe has antidepressant properties and pairing tDCS with cognitive training results in additional benefit due to enhancement of frontal cortical activity. However, these studies have primarily targeted depressed adults under age 65 years and less is known about whether this intervention combination is beneficial or affects subthreshold depressive symptoms in older adults. Participants and Methods: We are reporting secondary data analyses from Nissim et al. (2019), who recruited 30 non-demented healthy older adults and randomized them to receive active or sham tDCS in combination with cognitive training for 2 weeks. Active tDCS was delivered bifrontally over F3 (cathode) and F4 (anode) for 20-min at 2 mA intensity through two 5x7 cm2 saline saturated sponge electrodes using the Soterix Medical 1x1 tDCS clinical trials device. Sham tDCS had identical set-up with 2 mA stimulation for 30-sec with 30-sec ramp up and down. Cognitive training was administered for 40-min daily using attention/processing speed and working memory modules from BrainHQ. The first 20-min of cognitive training was paired with active or sham tDCS. To allow room for symptom improvement, we only included participants with Beck Depression Inventory, 2nd edition (BDI-II) scores of 5 or greater ("minimal" depression severity). We identified 15 participants who met this cut-off (70.93 ± 5.41 years old, 10 females, 16.4 years ± 2.32 years education, MoCA = 27.27 ± 2.34; 7 active, 8 sham). Results: tDCS conditions did not significantly differ in age, sex, years of education, MoCA scores, number of completed intervention days, or baseline BDI-II (active: 7.71 ± 2.93, sham: 11.38 ± 6.44). There were no differences in sensation ratings between groups or in confidence ratings for condition received (suggesting successful blinding). Results indicated the combination of active (and not sham) tDCS with cognitive training was associated with reduced depressive symptoms (2.7 vs. 1.4 points, active vs. sham). Including covariates (age, sex, education, MoCA scores, and number of completed intervention days) in the model further strengthened this discrepancy (3.7 vs. 0.51 points, active vs. sham). Conclusions: While preliminary, these results suggest this intervention combination may be a potential method for improving subthreshold depressive symptoms in older adults via targeting prefrontal neural circuitry and promoting neuroplasticity of the underlying neural network. While baseline BDI-II scores did not significantly differ, the active tDCS group had a lower score than sham, but saw greater improvement in BDI-II scores post-intervention despite having less room for change. Adequate treatment of subthreshold depressive symptoms may prevent or reduce negative outcomes associated with depressive symptoms in at-risk older adults. Larger randomized clinical trials are needed to better understand tDCS plus cognitive training antidepressant effects in this age group. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Working memory, a fundamental short-term cognitive process, is known to decline with advanced age even in healthy older adults. Normal age-related declines in working memory can cause loss of independence and decreased quality of life. Cognitive training has shown some potential at enhancing certain cognitive processes, although, enhancements are variable. Transcranial direct current stimulation (tDCS), a form of non-invasive brain stimulation, has shown promise at enhancing working memory abilities, and may further the benefits from cognitive training interventions. However, the neural mechanisms underlying tDCS brain-based enhancements remain unknown. Objective/Hypothesis: Assess the effects of a 2-week intervention of active-tDCS vs. sham paired with cognitive training on functional connectivity of the working memory network during an N-Back working memory task. Methods: Healthy older adults (N = 28; mean age = 74 ± 7.3) completed 10-sessions of cognitive training paired with active or sham-tDCS. Functional connectivity was evaluated at baseline and post-intervention during an N-Back task (2-Back vs. 0-Back). Results: Active-tDCS vs. sham demonstrated a significant increase in connectivity between the left dorsolateral prefrontal cortex and right inferior parietal lobule at post-intervention during 2-Back. Target accuracy on 2-Back was significantly improved for active vs. sham at post-intervention. Conclusion: These results suggest pairing tDCS with cognitive training enhances functional connectivity and working memory performance in older adults, and thus may hold promise as a method for remediating age-related cognitive decline. Future studies evaluating optimal dose and long-term effects of tDCS on brain function will help to maximize potential clinical impacts of tDCS paired with cognitive training in older adults. Clinical Trial Registration: www.ClinicalTrials.gov, identifier NCT02137122. [ABSTRACT FROM AUTHOR]

The objective of this study was to examine combination speed of processing (SOP) cognitive remediation therapy (CRT) and transcranial direct stimulation (tDCS) as neurorehabilitation in older HIV+ adults. Thirty-three HIV+ adults aged 50+ completed neurocognitive testing and were randomized to either active (n = 17) or sham (n = 16) tDCS. Both conditions received 10 1-hour sessions of SOP CRT, with either active or sham tDCS for the first 20 minutes. Participants then completed a posttest assessment. Repeated measures analysis of variance examining Time X Condition showed small-to-medium effects in the expected direction for an executive (d = 0.36), and SOP measure (d = 0.49), while medium-to-large effects were observed for an executive/attention (d = 0.60) and oral reading measure (d = 0.75). The only statistically significant interaction was the oral reading measure. Small-to-medium and medium-to-large effects (ds = 0.32, 0.58) were found for two SOP measures in the opposite direction (sham group showing greater improvements). Further trials of CRT and tDCS in this population are needed, including larger samples and a nonactive control and tDCS only condition, as is determination of which parameters of each technique (e.g., tDCS montage, timing of tDCS, domain targeted in CRT, number of sessions) are most effective in improving cognitive outcomes, durability of training gains, and translation to everyday functioning. [ABSTRACT FROM AUTHOR]

Background Adults over age 65 represent the fastest growing population in the US. Decline in cognitive abilities is a hallmark of advanced age and is associated with loss of independence and dementia risk. There is a pressing need to develop effective interventions for slowing or reversing the cognitive aging process. While certain forms of cognitive training have shown promise in this area, effects only sometimes transfer to neuropsychological tests within or outside the trained domain. This paper describes a NIA-funded Phase III adaptive multisite randomized clinical trial, examining whether transcranial direct current stimulation (tDCS) of frontal cortices enhances neurocognitive outcomes achieved from cognitive training in older adults experiencing age-related cognitive decline: the Augmenting Cognitive Training in Older Adults study (ACT). Methods ACT will enroll 360 participants aged 65 to 89 with age-related cognitive decline, but not dementia. Participants will undergo cognitive training intervention or education training-control combined with tDCS or sham tDCS control. Cognitive training employs a suite of eight adaptive training tasks focused on attention/speed of processing and working memory from Posit Science BrainHQ. Training control involves exposure to educational nature/history videos and related content questions of the same interval/duration as the cognitive training. Participants are assessed at baseline, after training (12 weeks), and 12-month follow-up on our primary outcome measure, NIH Toolbox Fluid Cognition Composite Score, as well as a comprehensive neurocognitive, functional, clinical and multimodal neuroimaging battery. Significance The findings from this study have the potential to significantly enhance efforts to ameliorate cognitive aging and slow dementia. [ABSTRACT FROM AUTHOR]

Objective Training in a divided attention/speed-of-processing task called Useful Field of View (UFOV) reduced dementia risk in older adults. Higher connectivity in resting-state networks involved in attention/inter-network modulation (cingulo-opercular network(CON); frontoparietal control network(FPCN)) relates to better UFOV performance. Cognitive status relates to CON connectivity and UFOV performance. Therefore, it may be an important third variable to consider. This study assessed the mediation of cognitive status on the relationship between CON/FPCN connectivity and UFOV performance. Methods 266 healthy older adults (age M = 71.4, SD = 5.18; 92% Caucasian) were recruited through a clinical trial at the University of Florida and the University of Arizona. Cognitive status was defined by the NIH Toolbox Fluid Composite score, assessing processing speed, attention/inhibition, executive functioning, and working/episodic memory. UFOV via the Double Decision assessment was administered. Participants underwent resting-state functional magnetic resonance imaging. Average within-network connectivity of CON and FPCN were extracted with the CONN Toolboxv18b via SPM12. Mediation of cognitive status on the relationship between CON/FPCN connectivity and UFOV performance was assessed controlling for sex, age, education, and site. Results Cognitive status fully mediated the indirect effect of CON on UFOV [b = −0.1776; 95%CI (−0.3194, −0.0684)] Figure 1, and FPCN on UFOV [b = −0.1461; 95%CI (−0.2934, −0.0342)] Figure 2. Conclusions Cognitive status accounted in part for the association between CON/FPCN connectivity and UFOV performance. Older adults with higher cognitive status had stronger functional connectivity and better UFOV performance. Future research should explore the influence of cognitive status on functional connectivity after UFOV training, and investigate which cognitive domains are most influential. [ABSTRACT FROM AUTHOR]

To address the rising prevalence of Alzheimer's disease and related dementias, effective interventions that can be widely disseminated are warranted. The Preventing Alzheimer's with Cognitive Training study (PACT) investigates a commercially available computerized cognitive training program targeting improved Useful Field of View Training (UFOVT) performance. The primary goal is to test the effectiveness of UFOVT to reduce incidence of clinically defined mild cognitive impairment (MCI) or dementia with a secondary objective to examine if effects are moderated by plasma β-amyloid level or apolipoprotein E e4 (APOE e4) allele status. This multisite study utilizes a randomized, controlled experimental design with blinded assessors and investigators. Individuals who are 65 years of age and older are recruited from the community. Eligible participants who demonstrate intact cognitive status (Montreal Cognitive Assessment score > 25) are randomized and asked to complete 45 sessions of either a commercially available computerized-cognitive training program (UFOVT) or computerized games across 2.5 years. After three years, participants are screened for cognitive decline. For those demonstrating decline or who are part of a random subsample, a comprehensive neuropsychological assessment is completed. Those who perform below a pre-specified level are asked to complete a clinical evaluation, including an MRI, to ascertain clinical diagnosis of normal cognition, MCI, or dementia. Participants are asked to provide blood samples for analyses of Alzheimer's disease related biomarkers. The PACT study addresses the rapidly increasing prevalence of dementia. Computerized cognitive training may provide a non-pharmaceutical option for reducing incidence of MCI or dementia to improve public health. Registration: The PACT study is registered at http://Clinicaltrials.gov NCT03848312 [ABSTRACT FROM AUTHOR]