Experimentally Induced Reductions in Alcohol Consumption and Brain, Cognitive, and Clinical Outcomes in Older Persons With and Those Without HIV Infection (30-Day Challenge Study): Protocol for a Nonrandomized Clinical Trial.

BACKGROUND: Both alcohol consumption and HIV infection are associated with worse brain, cognitive, and clinical outcomes in older adults. However, the extent to which brain and cognitive dysfunction is reversible with reduction or cessation of drinking is unknown. OBJECTIVE: The 30-Day Challenge study was designed to determine whether reduction or cessation of drinking would be associated with improvements in cognition, reduction of systemic and brain inflammation, and improvement in HIV-related outcomes in adults with heavy drinking. METHODS: The study design was a mechanistic experimental trial, in which all participants received an alcohol reduction intervention followed by repeated assessments of behavioral and clinical outcomes. Persons were eligible if they were 45 years of age or older, had weekly alcohol consumption of 21 or more drinks (men) or 14 or more drinks (women), and were not at high risk of alcohol withdrawal. After a baseline assessment, participants received an intervention consisting of contingency management (money for nondrinking days) for at least 30 days followed by a brief motivational interview. After this, participants could either resume drinking or not. Study questionnaires, neurocognitive assessments, neuroimaging, and blood, urine, and stool samples were collected at baseline, 30 days, 90 days, and 1 year after enrollment. RESULTS: We enrolled 57 persons with heavy drinking who initiated the contingency management protocol (mean age 56 years, SD 4.6 years; 63%, n=36 male, 77%, n=44 Black, and 58%, n=33 people with HIV) of whom 50 completed 30-day follow-up and 43 the 90-day follow-up. The planned study procedures were interrupted and modified due to the COVID-19 pandemic of 2020-2021. CONCLUSIONS: This was the first study seeking to assess changes in brain (neuroimaging) and cognition after alcohol intervention in nontreatment-seeking people with HIV together with people without HIV as controls. Study design strengths, limitations, and lessons for future study design considerations are discussed. Planned analyses are in progress, after which deidentified study data will be available for sharing. TRIAL REGISTRATION: ClinicalTrials.gov NCT03353701; https://clinicaltrials.gov/study/NCT03353701. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53684.

Learning ratio performance on a brief visual learning and memory test moderates cognitive training gains in Double Decision task in healthy older adults.

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 was variability in the achievement of cognitive gains after cognitive training across studies, suggesting moderating factors. Learning trials of visual and verbal learning tasks recruit similar cognitive abilities and have overlapping neural correlates with speed-of-processing/working memory tasks and therefore could serve as potential moderators of cognitive training gains. This study explored the association between the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) learning with a commercial UFOV task called Double Decision. Through a secondary analysis of a clinical trial, we assessed the moderation of HVLT-R and BVMT-R learning on Double Decision improvement after a 3-month speed-of-processing/attention and working memory cognitive training intervention in a sample of 75 cognitively healthy older adults. Multiple linear regressions showed that better baseline Double Decision performance was significantly associated with better BVMT-R learning (ß = - .303). This association was not significant for HVLT-R learning (ß = - .142). Moderation analysis showed that those with poorer BVMT-R learning improved the most on the Double Decision task after cognitive training. This suggests that healthy older adults who perform below expectations on cognitive tasks related to the training task 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 and efficacy of the intervention.

The impact of a tDCS and cognitive training intervention on task-based functional connectivity.

Declines in several cognitive domains, most notably processing speed, occur in non-pathological aging. Given the exponential growth of the older adult population, declines in cognition serve as a significant public health issue that must be addressed. Promising studies have shown that cognitive training in older adults, particularly using the useful field of view (UFOV) paradigm, can improve cognition with moderate to large effect sizes. Additionally, meta-analyses have found that transcranial direct current stimulation (tDCS), a non-invasive form of brain stimulation, can improve cognition in attention/processing speed and working memory. However, only a handful of studies have looked at concomitant tDCS and cognitive training, usually with short interventions and small sample sizes. The current study assessed the effect of a tDCS (active versus sham) and a 3-month cognitive training intervention on task-based functional connectivity during completion of the UFOV task in a large older adult sample (N = 153). We found significant increased functional connectivity between the left and right pars triangularis (the ROIs closest to the electrodes) following active, but not sham tDCS. Additionally, we see trending behavioral improvements associated with these functional connectivity changes in the active tDCS group, but not sham. Collectively, these findings suggest that tDCS and cognitive training can be an effective modulator of task-based functional connectivity above and beyond a cognitive training intervention alone.

Preliminary evidence of transcutaneous vagus nerve stimulation effects on sleep in veterans with post-traumatic stress disorder.

Sleep problems are common among veterans with post-traumatic stress disorder and closely associated with hyperarousal symptoms. Transcutaneous vagus nerve stimulation (tVNS) may have potential to improve sleep quality in veterans with PTSD through effects on brain systems relevant to hyperarousal and sleep-wake regulation. The current pilot study examines the effect of 1 h of tVNS administered at "lights out" on sleep architecture, microstructure, and autonomic activity. Thirteen veterans with PTSD completed two nights of laboratory-based polysomnography during which they received 1 h of either active tVNS (tragus) or sham stimulation (earlobe) at "lights out" with randomised order. Sleep staging and stability metrics were derived from polysomnography data. Autonomic activity during sleep was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (RSAP-B ). Paired t-tests revealed a small decrease in the total sleep time (d = -0.31), increase in N3 sleep (d = 0.23), and a small-to-moderate decrease in REM sleep (d = -0.48) on nights of active tVNS relative to sham stimulation. tVNS was also associated with a moderate reduction in cyclic alternating pattern (CAP) rate (d = -0.65) and small-to-moderate increase in RSAP-B during NREM sleep. Greater NREM RSAP-B was associated with a reduced CAP rate and NREM alpha power. This pilot study provides preliminary evidence that tVNS may improve sleep depth and stability in veterans with PTSD, as well as increase parasympathetically mediated nocturnal autonomic activity. These results warrant continued investigation into tVNS as a potential tool for treating sleep disturbance in veterans with PTSD.

The association of depression and anxiety symptoms to three different types of activities of daily living in persons with and without HIV.

Mood disorders are highly prevalent in people living with HIV (PLWH) and represent a potential contributor to functional impairment in activities of daily living. We aimed to determine if (1) Anxiety and depression symptoms were independently associated with impairments in basic self-care, role functioning, and social functioning and (2) PLWH differentially experienced impairments due to mood symptoms compared to those without HIV. Data for this study were obtained from 150 individuals (87 PLWH, 61% male, mean age = 44) via a cross-sectional study on alcohol and HIV-associated brain dysfunction. The Beck Anxiety Inventory (BAI) and the Center for Epidemiologic Studies Depression Scale (CES-D) were used to assess anxiety and depressive symptoms. Higher anxiety symptoms were associated with role functioning impairment, while higher depressive and anxiety symptoms were each associated with social functioning impairment. As depressive symptoms increased, PLWH were 3x more likely to have impairments in role functioning compared to those without HIV. HIV status did not interact with mood symptoms to affect basic self-care or social functioning. Overall, mood symptoms are associated with different types of functional impairment, and improved management of mood symptoms could lead to improved role and social functioning.

Pet ownership is associated with harmful alcohol use among a cohort of people with HIV: a brief research report.

Research suggests that people with HIV (PWH), who are at high risk for alcohol and substance use, may rely on relationships with pets for companionship and stress relief. There may be common mechanisms underlying both substance use and attachment to pets. The purpose of this brief research report was to compare alcohol and substance use behaviors between pet owners and non-owners among a cohort of PWH. Participants (n = 735) in a survey study of PWH in Florida were asked about their alcohol and substance use behaviors, whether they owned a pet, and their sociodemographic characteristics. We used bivariate analyses and logistic regression to examine differences in alcohol and substance use behaviors between pet owners and non-owners. Pet owners had higher mean AUDIT scores than non-owners (Mpet = 5, Mnopet = 4, z = -3.07, p = 0.002). Pet owners were more likely than non-owners to use alcohol in a harmful or hazardous way (AUDIT score ≥ 8), above and beyond sociodemographic characteristics (OR = 1.65, p = 0.052). Pet owners were more likely to have ever used most substances than non-owners, and more likely to currently use alcohol (X2(1) = 12.97, p = 0.000), marijuana or hashish (X2(1) = 6.82, p = 0.009), and amyl nitrate/poppers (X2(1) = 11.18, p = 0.001). Pet owners may be more likely to use alcohol and other substances at higher rates than non-owners. Reasons for owning a pet and using substances may be similar, such as coping with stress.

Remotely supervised at-home delivery of taVNS for autism spectrum disorder: feasibility and initial efficacy.

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) has potential clinical application for autism spectrum disorder (ASD). At-home sessions are necessary to allow delivery of repeated sessions, and remove burden on patients for daily visits, and reduce costs of clinic delivery. Our objective was to validate a protocol for remote supervised administration for home delivery of taVNS using specially designed equipment and platform. Methods: An open-label design was followed involving administration by caretakers to 12 patients with ASD (ages:7-16). Daily 1-h sessions over 2 weeks were administered under remote supervision. The primary outcome was feasibility, which was assessed by completion rate, stimulation tolerability, and confirmation of programmed stimulation delivery. The secondary measures were initial efficacy assessed by Childhood Anxiety Sensitivity Index-Revised (CASI-R), Parent Rated Anxiety Scale for Youth with ASD (PRAS-ASD), and Clinician Global Impression (CGI) scales. Sleep measures were also tracked using Cleveland Adolescent Sleep Questionnaire (CASQ). Results: Across 132 sessions, we obtained an 88.5% completion rate. A total of 22 expected adverse events were reported with headache being the most common followed by transient pain, itchiness, and stinging at the electrode site. One subject dropped out of the study unrelated to the stimulation or the study. Average scores of anxiety (CASI-R, PRAS-ASD, and CGI) and sleepiness (CASQ) were all improved at the 2 week time point. While not powered to determine efficacy, benefits were suggested in this open label pilot. Conclusion: Remotely supervised, proxy-administered, at-home delivery of taVNS is feasible in patients with ASD. Initial efficacy supports pursuing larger scale trials.

Connecting memory and functional brain networks in older adults: a resting-state fMRI study.

Limited research exists on the association between resting-state functional network connectivity in the brain and learning and memory processes in advanced age. This study examined within-network connectivity of cingulo-opercular (CON), frontoparietal control (FPCN), and default mode (DMN) networks, and verbal and visuospatial learning and memory in older adults. Across domains, we hypothesized that greater CON and FPCN connectivity would associate with better learning, and greater DMN connectivity would associate with better memory. A total of 330 healthy older adults (age range = 65-89) underwent resting-state fMRI and completed the Hopkins Verbal Learning Test-Revised (HVLT-R) and Brief Visuospatial Memory Test-Revised (BVMT-R) in a randomized clinical trial. Total and delayed recall scores were assessed from baseline data, and a learning ratio calculation was applied to participants' scores. Average CON, FPCN, and DMN connectivity values were obtained with CONN Toolbox. Hierarchical regressions controlled for sex, race, ethnicity, years of education, and scanner site, as this was a multi-site study. Greater within-network CON connectivity was associated with better verbal learning (HVLT-R Total Recall, Learning Ratio), visuospatial learning (BVMT-R Total Recall), and visuospatial memory (BVMT-R Delayed Recall). Greater FPCN connectivity was associated with better visuospatial learning (BVMT-R Learning Ratio) but did not survive multiple comparison correction. DMN connectivity was not associated with these measures of learning and memory. CON may make small but unique contributions to learning and memory across domains, making it a valuable target in future longitudinal studies and interventions to attenuate memory decline. Further research is necessary to understand the role of FPCN in learning and memory.

Impact of transcutaneous vagus nerve stimulation on healthy cognitive and brain aging.

Evidence for clinically meaningful benefits of transcutaneous vagus nerve stimulation (VNS) has been rapidly accumulating over the past 15 years. This relatively novel non-invasive brain stimulation technique has been applied to a wide range of neuropsychiatric disorders including schizophrenia, obsessive compulsive disorder, panic disorder, post-traumatic stress disorder, bipolar disorder, and Alzheimer's disease. More recently, non-invasive forms of VNS have allowed for investigations within healthy aging populations. These results offer insight into protocol considerations specific to older adults and how to translate those results into effective clinical trials and, ultimately, effective clinical care. In this review, we characterize the possible mechanisms by which non-invasive VNS may promote healthy aging (e.g., neurotransmitter effects, inflammation regulation, functional connectivity changes), special considerations for applying non-invasive VNS in an older adult population (e.g., vagus nerve changes with age), and how non-invasive VNS may be used in conjunction with existing behavioral interventions (e.g., cognitive behavioral therapy, cognitive training) to promote healthy emotional and cognitive aging.

Effects of sleep disturbance on trauma-focused psychotherapy outcomes in posttraumatic stress disorder: A systematic review.

This study aimed to synthesize existing research on the effects of sleep disturbances on trauma-focused psychotherapy outcomes in adults with posttraumatic stress disorder (PTSD). A systematic review using PubMed, PsycINFO, Embase, Web of Science, and PTSDpubs was performed up to April 2021. Two independent reviewers screened articles for inclusion, performed data extraction, and assessed risk of bias and certainty of the evidence. Narrative synthesis was conducted based on the type of sleep disorder symptom assessed. Sixteen primary studies were included in this review, the majority of which had a high overall risk of bias. Results suggested that sleep disorder symptoms were associated with higher overall PTSD severity across treatment; however, they did not interfere with treatment effectiveness, with the exception of sleep-disordered breathing. Improvements in insomnia, sleep duration, and sleep quality during treatment were associated with greater treatment gains. Certainty of the evidence ranged from low to very low. These results suggest that it may not be necessary to address sleep disorder symptoms prior to initiating trauma-focused psychotherapy. Instead, concurrent treatment of sleep- and trauma-related symptoms may be most beneficial. Continued research is needed to clarify the mechanistic relationship between sleep and treatment outcomes and to guide clinical decision-making.

Resting state connectivity in people living with HIV before and after stopping heavy drinking.

Background: Heavy alcohol use in people living with HIV (PLWH) has widespread negative effects on neural functioning. It remains unclear whether experimentally-induced reduction in alcohol use could reverse these effects. We sought to determine the effects of 30-days drinking cessation/reduction on resting state functional connectivity in people with and without HIV. Methods: Thirty-five participants (48.6% PLWH) demonstrating heavy alcohol use attempted to stop drinking for 30 days via contingency management (CM). MRI was acquired at baseline and after thirty days, and functional connectivity across five resting-state fMRI (rsfMRI) networks was calculated with the Conn toolbox for Matlab and examined in relation to transdermal alcohol concentration (TAC) recorded by the ankle-worn secure continuous remote alcohol monitor (SCRAM) and self-reported alcohol use (timeline follow-back; TLFB). Associations between alcohol use and reduction, HIV status, functional connectivity, and change in functional connectivity across five major rsfMRI networks were determined relative to the pre- and post-CM timepoints. Results: Baseline resting-state functional connectivity was not significantly associated with average TAC-AUC during the pre-CM period, though higher self-reported alcohol use over the preceding 30 days was significantly associated with higher baseline connectivity within the Dorsal Attention Network (DAN; p-FDR < 0.05). Baseline connectivity within the Salience network was significantly negatively related to objective drinking reduction after intervention (DAN; p-FDR < 0.05), whereas baseline connectivity within the Limbic network was positively associated with self-reported drinking reduction (p-FDR < 0.05). Change in between-networks functional connectivity after intervention was significantly positively associated with biosensor-confirmed drinking reduction such that higher reduction was associated with stronger connectivity between the limbic and fronto-parietal control networks (p-FDR < 0.05). PLWH with lower DAN connectivity at baseline demonstrated poorer alcohol reduction than those with higher DAN connectivity at baseline. Discussion: Lower resting-state functional connectivity of the Salience network significantly predicted stronger drinking reduction across all participants, suggesting a potential biomarker for reduced susceptibility to the environmental and social cues that often make alcohol use reduction attempts unsuccessful. Increased between-networks connectivity was observed in participants with higher alcohol reduction after CM, suggesting a positive benefit to brain connectivity associated with reduced drinking. PLWH with lower baseline DAN connectivity may not benefit as greatly from CM for alcohol reduction.

Change in medial frontal cerebral metabolite concentrations following bariatric surgery.

Obesity is associated with adverse effects on brain health, including an increased risk of neurodegenerative diseases. Changes in cerebral metabolism may underlie or precede structural and functional brain changes. While bariatric surgery is known to be effective in inducing weight loss and improving obesity-related medical comorbidities, few studies have examined whether it may be able to improve brain metabolism. In the present study, we examined changes in cerebral metabolite concentrations in participants with obesity who underwent bariatric surgery. Thirty-five patients with obesity (body mass index ≥ 35 kg/m2 ) were recruited from a bariatric surgery candidate nutrition class. They completed single voxel proton magnetic resonance spectroscopy at baseline (presurgery) and within 1 year postsurgery. Spectra were obtained from a large medial frontal brain region using a PRESS sequence on a 3-T Siemens Verio scanner. The acquisition parameters were TR = 3000 ms and TE = 37 ms. Tissue-corrected metabolite concentrations were determined using Osprey. Paired t-tests were used to examine within-subject change in metabolite concentrations, and correlations were used to relate these changes to other health-related outcomes, including weight loss and glycated hemoglobin (HbA1c ), a measure of blood sugar levels. Bariatric surgery was associated with a reduction in cerebral choline-containing compounds (Cho; t [34] = - 3.79, p < 0.001, d = -0.64) and myo-inositol (mI; t [34] = - 2.81, p < 0.01, d = -0.47) concentrations. There were no significant changes in N-acetyl-aspartate, creatine, or glutamate and glutamine concentrations. Reductions in Cho were associated with greater weight loss (r = 0.40, p < 0.05), and reductions in mI were associated with greater reductions in HbA1c (r = 0.44, p < 0.05). In conclusion, participants who underwent bariatric surgery exhibited reductions in cerebral Cho and mI concentrations, which were associated with improvements in weight loss and glycemic control. Given that elevated levels of Cho and mI have been implicated in neuroinflammation, reduction in these metabolites after bariatric surgery may reflect amelioration of obesity-related neuroinflammatory processes. As such, our results provide evidence that bariatric surgery may improve brain health and metabolism in individuals with obesity.

Using alcohol biosensors and biomarkers to measure changes in drinking: Associations between transdermal alcohol concentration, phosphatidylethanol, and self-report in a contingency management study of persons with and without HIV.

Alcohol use can be measured in many ways, including objectively through transdermal alcohol biosensors (e.g., transdermal alcohol concentration; TAC) or blood biomarkers (e.g., phosphatidylethanol; PEth), or subjectively through self-report (e.g., with the timeline followback; TLFB). However, it is unclear which measures best indicate changes in alcohol use within individuals following intervention, and if they have concurrent validity. In the context of contingency management (CM) with a goal of 30-day abstinence (n = 45, 60% male, 80% Black; Mage = 56.7; 58% with HIV), we examined relationships among changes in TAC-AUC (area under the curve, reflecting volume consumed), PEth, and self-reported number of drinks. The Secure Continuous Remote Alcohol Monitor Continuous Alcohol Monitoring (SCRAM-CAM) biosensor was used to collect TAC-AUC during a pre-CM period (∼7 days) and over a 30-day CM period. PEth was collected at baseline and 30-day follow-up. Number of drinks was self-reported through a 30-day TLFB at baseline and follow-up. Daily TAC-AUC and number of self-reported drinks were calculated for the pre-CM period and for the last 7 days of the CM period. Linear regression models controlling for baseline values revealed that change in TAC-AUC was significantly associated with change in PEth (ß = 0.33, p < .0001) and with change in number of self-reported drinks (ß = 0.34, p < .0001). Change in PEth was significantly associated with change in number of self-reported drinks (ß = 0.85, p < .0001). We conclude that all three measures may be appropriate for measuring within-person change in alcohol use, while controlling for baseline values, in the context of a study testing an intervention such as CM. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Protocol for a pilot and feasibility randomized-controlled trial of four weeks of oral γ-aminobutyric acid (GABA) intake and its effect on pain and sleep in middle-to-older aged adults.

Approximately 1.71 billion people globally live with musculoskeletal pain conditions, including low back pain, knee pain, and neck pain Cieza et al. (2020). In the US, an estimated 20.4% of U.S. adult had chronic pain and 8.0% of U.S. adults had high-impact chronic pain, with higher prevalence associated with advancing age Dahlhamer et al. (2018). On the other hand, between 50 and 70 million US adults have a sleep disorder (American Sleep Association). Although the link between sleep and pain is widely established, the neurobiological mechanisms underlying this relationship have yet to be fully elucidated, specifically within an aged population. As currently available sleep and chronic pain therapies are only partially effective, novel treatment approaches are urgently needed. Given the potential mechanistic role of γ-aminobutyric acid (GABA) in both conditions, and the availability of GABA supplements over the counter, the present proposal will determine the feasibility and acceptability of oral GABA administration in middle-to-older aged adults with chronic pain and sleep disorders as well as characterize the potential neurobiological mechanisms involved in both conditions. Results from the present investigation using a parallel, double-blinded, placebo-controlled study will provide novel preliminary information needed for future translational pain and sleep research.

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.

Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample.

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.

The Effects of Transcutaneous Vagus Nerve Stimulation on Functional Connectivity Within Semantic and Hippocampal Networks in Mild Cognitive Impairment.

Better treatments are needed to improve cognition and brain health in people with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Transcutaneous vagus nerve stimulation (tVNS) may impact brain networks relevant to AD through multiple mechanisms including, but not limited to, projection to the locus coeruleus, the brain's primary source of norepinephrine, and reduction in inflammation. Neuropathological data suggest that the locus coeruleus may be an early site of tau pathology in AD. Thus, tVNS may modify the activity of networks that are impaired and progressively deteriorate in patients with MCI and AD. Fifty patients with MCI (28 women) confirmed via diagnostic consensus conference prior to MRI (sources of info: Montreal Cognitive Assessment Test (MOCA), Clinical Dementia Rating scale (CDR), Functional Activities Questionnaire (FAQ), Hopkins Verbal Learning Test - Revised (HVLT-R) and medical record review) underwent resting state functional magnetic resonance imaging (fMRI) on a Siemens 3 T scanner during tVNS (left tragus, n = 25) or sham control conditions (left ear lobe, n = 25). During unilateral left tVNS, compared with ear lobe stimulation, patients with MCI showed alterations in functional connectivity between regions of the brain that are important in semantic and salience functions including regions of the temporal and parietal lobes. Furthermore, connectivity from hippocampi to several cortical and subcortical clusters of ROIs also demonstrated change with tVNS compared with ear lobe stimulation. In conclusion, tVNS modified the activity of brain networks in which disruption correlates with deterioration in AD. These findings suggest afferent target engagement of tVNS, which carries implications for the development of noninvasive therapeutic intervention in the MCI population.

Task-based functional connectivity of the Useful Field of View (UFOV) fMRI task.

Declines in processing speed performance occur in aging and are a critical marker of functional independence in older adults. Numerous studies suggest that Useful Field of View (UFOV) training may ameliorate cognitive decline in older adults. Despite its efficacy, little is known about the neural correlates of this task. The current study is the first to investigate the coherence of functional connectivity during UFOV task completion. A total of 336 participants completed the UFOV task while undergoing task-based functional magnetic resonance imaging (fMRI). Ten spherical regions of interest (ROIs), selected a priori, were created based on regions with the greatest peak BOLD activation patterns in the UFOV fMRI task and regions that have been shown to significantly relate to UFOV fMRI task performance. We used a weighted ROI-to-ROI connectivity analysis to model task-specific functional connectivity strength between these a priori selected ROIs. We found that our UFOV fMRI network was functionally connected during task performance and was significantly associated to UFOV fMRI task performance. Within-network connectivity of the UFOV fMRI network showed comparable or better predictive power in accounting for UFOV accuracy compared to 7 resting state networks, delineated by Yeo and colleagues. Finally, we demonstrate that the within-network connectivity of UFOV fMRI task accounted for scores on a measure of "near transfer", the Double Decision task, better than the aforementioned resting state networks. Our data elucidate functional connectivity patterns of the UFOV fMRI task. This may assist in future targeted interventions that aim to improve synchronicity within the UFOV fMRI network.

The longitudinal impact of the COVID-19 pandemic on health behaviors, psychosocial factors, and cognitive functioning in older adults.

Background: Older adults are at a greater risk for contracting and experiencing severe illness from COVID-19 and may be further affected by pandemic-related precautions (e.g., social distancing and isolation in quarantine). However, the longitudinal impact of the COVID-19 pandemic on older adults is unclear. The current study examines changes in health behaviors, psychosocial factors, and cognitive functioning in a large sample of older adults using a pre-pandemic baseline and longitudinal follow-up throughout 9 months of the COVID-19 pandemic. Methods: One hundred and eighty-nine older adults (ages 65-89) were recruited from a multisite clinical trial to complete additional virtual assessments during the COVID-19 pandemic. Mixed effects models evaluated changes in health behaviors, psychosocial factors, and cognitive functioning during the pandemic compared to a pre-pandemic baseline and over the course of the pandemic (i.e., comparing the first and last COVID-19 timepoints). Results: Compared to their pre-pandemic baseline, during the pandemic, older adults reported worsened sleep quality, perceived physical health and functioning, mental health, slight increases in depression and apathy symptoms, reduced social engagement/perceived social support, but demonstrated better performance on objective cognitive tasks of attention and working memory. Throughout the course of the pandemic, these older adults reported continued worsening of perceived physical health and function, fewer depression symptoms, and they demonstrated improved cognitive performance. It is important to note that changes on self-report mood measures and cognitive performance were relatively small regarding clinical significance. Education largely served as a protective factor, such that greater years of education was generally associated with better outcomes across domains. Conclusions: The present study provides insights into the longitudinal impact of the COVID-19 pandemic on health behaviors, psychosocial factors, and cognitive functioning in a population disproportionately affected by the virus. Replicating this study design in a demographically representative older adult sample is warranted to further inform intervention strategies targeting older adults negatively impacted by the COVID-19 pandemic.

Functional connectivity of brain networks during semantic processing in older adults.

The neural systems underlying semantic processing have been characterized with functional neuroimaging in young adults. Whether the integrity of these systems degrade with advanced age remains unresolved. The current study examined functional connectivity during abstract and concrete word processing. Thirty-eight adults, aged 55-91, engaged in semantic association decision tasks during a mixed event-related block functional magnetic resonance imaging (fMRI) paradigm. During the semantic trials, the task required participants to make a judgment as to whether pairs were semantically associated. During the rhyme trials, the task required participants to determine if non-word pairs rhymed. Seeds were placed in putative semantic hubs of the left anterior middle temporal gyrus (aMTG) and the angular gyrus (AG), and also in the left inferior frontal gyrus (IFG), an area considered important for semantic control. Greater connectivity between aMTG, AG, and IFG and multiple cortical areas occurred during semantic processing. Connectivity from the three seeds differed during semantic processing: the left AG and aMTG were strongly connected with frontal, parietal, and occipital areas bilaterally, whereas the IFG was most strongly connected with other frontal cortical areas and the AG in the ipsilateral left hemisphere. Notably, the strength and extent of connectivity differed for abstract and concrete semantic processing; connectivity from the left aMTG and AG to bilateral cortical areas was greater during abstract processing, whereas IFG connectivity with left cortical areas was greater during concrete processing. With advanced age, greater connectivity occurred only between the left AG and supramarginal gyrus during the processing of concrete word-pairs, but not abstract word-pairs. Among older adults, robust functional connectivity of the aMTG, AG, and IFG to widely distributed bilateral cortical areas occurs during abstract and concrete semantic processing in a manner consistent with reports from past studies of young adults. There was not a significant degradation of functional connectivity during semantic processing between the ages of 55 and 85 years. As the study focused on semantic functioning in older adults, a comparison group of young adults was not included, limiting generalizability. Future longitudinal neuroimaging studies that compare functional connectivity of young and older adults under different semantic demands will be valuable.