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.

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.

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.

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.

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.

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.

Neurometabolic timecourse of healthy aging.

PURPOSE: The neurometabolic timecourse of healthy aging is not well-established, in part due to diversity of quantification methodology. In this study, a large structured cross-sectional cohort of male and female subjects throughout adulthood was recruited to investigate neurometabolic changes as a function of age, using consensus-recommended magnetic resonance spectroscopy quantification methods. METHODS: 102 healthy volunteers, with approximately equal numbers of male and female participants in each decade of age from the 20s, 30s, 40s, 50s, and 60s, were recruited with IRB approval. MR spectroscopic data were acquired on a 3T MRI scanner. Metabolite spectra were acquired using PRESS localization (TE=30 ms; 96 transients) in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Water-suppressed spectra were modeled using the Osprey algorithm, employing a basis set of 18 simulated metabolite basis functions and a cohort-mean measured macromolecular spectrum. Pearson correlations were conducted to assess relationships between metabolite concentrations and age for each voxel; Spearman correlations were conducted where metabolite distributions were non-normal. Paired t-tests were run to determine whether metabolite concentrations differed between the PCC and CSO. Finally, robust linear regressions were conducted to assess both age and sex as predictors of metabolite concentrations in the PCC and CSO and separately, to assess age, signal-noise ratio, and full width half maximum (FWHM) linewidth as predictors of metabolite concentrations. RESULTS: Data from four voxels were excluded (2 ethanol; 2 unacceptably large lipid signal). Statistically-significant age*metabolite Pearson correlations were observed for tCho (r(98)=0.33, p<0.001), tCr (r(98)=0.60, p<0.001), and mI (r(98)=0.32, p=0.001) in the CSO and for NAAG (r(98)=0.26, p=0.008), tCho(r(98)=0.33, p<0.001), tCr (r(98)=0.39, p<0.001), and Gln (r(98)=0.21, p=0.034) in the PCC. Spearman correlations for non-normal variables revealed a statistically significant correlation between sI and age in the CSO (r(86)=0.26, p=0.013). No significant correlations were seen between age and tNAA, NAA, Glx, Glu, GSH, PE, Lac, or Asp in either region (all p>0.20). Age associations for tCho, tCr, mI and sI in the CSO and for NAAG, tCho, and tCr in the PCC remained when controlling for sex in robust regressions. CSO NAAG and Asp, as well as PCC tNAA, sI, and Lac were higher in women; PCC Gln was higher in men. When including an age*sex interaction term in robust regression models, a significant age*sex interaction was seen for tCho (F(1,96)=11.53, p=0.001) and GSH (F(1,96)=7.15, p=0.009) in the CSO and tCho (F(1,96)=9.17, p=0.003), tCr (F(1,96)=9.59, p=0.003), mI (F(1,96)=6.48, p=0.012), and Lac (F(1,78)=6.50, p=0.016) in the PCC. In all significant interactions, metabolite levels increased with age in females, but not males. There was a significant positive correlation between linewidth and age. Age relationships with tCho, tCr, and mI in the CSO and tCho, tCr, mI, and sI in the PCC were significant after controlling for linewidth and FWHM in robust regressions. CONCLUSION: The primary (correlation) results indicated age relationships for tCho, tCr, mI, and sI in the CSO and for NAAG, tCho, tCr, and Gln in the PCC, while no age correlations were found for tNAA, NAA, Glx, Glu, GSH, PE, Lac, or Asp in either region. Our results provide a normative foundation for future work investigating the neurometabolic time course of healthy aging using MRS.

The Association Between Peripheral Oxytocin Levels and Depressive Symptoms in People With HIV.

OBJECTIVE: Depression is common in people with HIV (PWH), yet little is known about the mechanisms contributing to depressive symptoms in PWH. Previous research across a range of populations has suggested a relationship between the neuropeptide oxytocin and depressive symptoms, with variable directionality. This article investigated the association between peripheral oxytocin levels and depressive symptoms in PWH. METHODS: Unextracted oxytocin serum concentrations were assayed in 79 PWH (44% female, mean age = 34.35 [8.5], mean body mass index = 25.69 [5.46], mean CD4 = 516.60 [271.15]) who also completed the Center for Epidemiologic Studies Depression Scale (CES-D). CES-D items were evaluated in an exploratory factor analysis (EFA), and the relationships between oxytocin, total CES-D score, and the resulting EFA factors were analyzed with multivariate linear regressions conducted in R. Multiple regression models were used to adjust for age, sex, body mass index, CD4, and education. RESULTS: Contrary to hypothesized, higher peripheral oxytocin levels were associated with higher CES-D total scores with a small-to-moderate effect size ( ß = 0.26, p = .009). Following Bonferroni correction, oxytocin was not significantly associated with any of the five factors identified from the EFA: depressed affect, positive affect, appetite, cognitive symptoms, or perceived failure ( p values > .042). Small effect sizes were found for the depressed affect ( ß = 0.22) and perceived failure ( ß = 0.21) factors ( p values > .042). CONCLUSIONS: In a sample of predominately Black or African American individuals with HIV, higher oxytocin was associated with higher total depressive symptoms. In addition, this relationship was slightly stronger than those of specific depressive symptoms. These findings warrant further study into the role of oxytocin in mood symptoms within PWH.

Higher white matter hyperintensity load adversely affects pre-post proximal cognitive training performance in healthy older adults.

Cognitive training has shown promise for improving cognition in older adults. Age-related neuroanatomical changes may affect cognitive training outcomes. White matter hyperintensities are one common brain change in aging reflecting decreased white matter integrity. The current study assessed (1) proximal cognitive training performance following a 3-month randomized control trial and (2) the contribution of baseline whole-brain white matter hyperintensity load, or total lesion volume (TLV), on pre-post proximal training change. Sixty-two healthy older adults were randomized to either adaptive cognitive training or educational training control interventions. Repeated-measures analysis of covariance 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 education training 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. These findings demonstrate the utility of cognitive training for improving post-intervention proximal performance in older adults. Additionally, pre-post proximal processing speed training change appears 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.

The macromolecular MR spectrum does not change with healthy aging.

PURPOSE: To acquire the mobile macromolecule (MM) spectrum from healthy participants, and to investigate changes in the signals with age and sex. METHODS: 102 volunteers (49 M/53 F) between 20 and 69 years were recruited for in vivo data acquisition in the centrum semiovale (CSO) and posterior cingulate cortex (PCC). Spectral data were acquired at 3T using PRESS localization with a voxel size of 30 × 26 × 26 mm3 , pre-inversion (TR/TI 2000/600 ms) and CHESS water suppression. Metabolite-nulled spectra were modeled to eliminate residual metabolite signals, which were then subtracted out to yield a "clean" MM spectrum using the Osprey software. Pearson's correlation coefficient was calculated between integrals and age for the 14 MM signals. One-way ANOVA was performed to determine differences between age groups. An independent t-test was carried out to determine differences between sexes. RESULTS: MM spectra were successfully acquired in 99 (CSO) and 96 (PCC) of 102 subjects. No significant correlations were seen between age and MM signals. One-way ANOVA also suggested no age-group differences for any MM peak (all p > .004). No differences were observed between sex groups. WM and GM voxel fractions showed a significant (p < .05) negative linear association with age in the WM-predominant CSO (R = -0.29) and GM-predominant PCC regions (R = -0.57) respectively while CSF increased significantly with age in both regions. CONCLUSION: Our findings suggest that a pre-defined MM basis function can be used for linear combination modeling of metabolite data from different age and sex groups.

Subjective Cognitive Complaints: Predictors and Health Outcomes in People Living with HIV.

There is a paucity of research on the prevalence of subjective cognitive complaints in people living with human immunodeficiency virus, along with the predictors and outcomes related to these complaints. We assessed demographics, substance use and psychiatric predictors, and HIV-related outcomes associated with subjective cognitive complaint items from the Cognitive Difficulties Scale. The sample consisted of 889 people living with HIV in the survey-based Florida Cohort. Results of multivariable regression models indicated that age (45-54), hazardous alcohol consumption, more frequent marijuana use and psychiatric symptoms (depression, anxiety, PTSD) were significant predictors of subjective cognitive complaints. Subjective cognitive complaints were associated with lower adherence to antiretroviral therapy in bivariate analyses, but this relationship was no longer significant after controlling for depression, race, alcohol and drug use. Further research into the relationship between depressive and subjective cognitive complaints may provide additional avenues for intervention.

RESUMEN: Existe una escasez de investigación sobre la prevalencia de quejas cognitivas subjetivas en personas que viven con el virus de la inmunodeficiencia humana (VIH), junto con los predictores y los resultados relacionados con estas quejas. Evaluamos la demografía, el uso de sustancias y los predictores psiquiátricos, y los resultados relacionados con el VIH asociados con los ítems de quejas cognitivas subjetivas de la Escala de Dificultades Cognitivas. La muestra consistió en 889 personas que viven con el VIH en la cohorte de Florida basada en la encuesta. Los resultados de los modelos de regresión multivariable indicaron que la edad (45-54), el consumo peligroso de alcohol, el uso más frecuente de marihuana y los síntomas psiquiátricos (depresión, ansiedad, trastorno de estrés postraumático) fueron predictores significativos de quejas cognitivas subjetivas. Las quejas cognitivas subjetivas se asociaron con una menor adherencia a la terapia antirretroviral en los análisis bivariados, pero esta relación dejó de ser significativa después de controlar la depresión, la raza, el alcohol y el consumo de drogas. La investigación adicional sobre la relación entre las quejas cognitivas depresivas y subjetivas puede proporcionar vías adicionales de intervención.

Resting-state functional connectivity patterns are associated with worst pain duration in community-dwelling older adults.

INTRODUCTION: An individual's chronic pain history is associated with brain morphometric alterations; but little is known about the association between pain history and brain function. OBJECTIVES: This cross-sectional study aimed at determining how worst musculoskeletal pain intensity (WPINT) moderated the association between worst musculoskeletal pain duration (WPDUR) and brain resting-state magnetic resonance imaging functional connectivity (RSFC) in community-dwelling older adults (60-94 years, 75% females, 97% right-handed). METHODS: Resting-state magnetic resonance imaging functional connectivity between region of interests was linearly regressed on WPDUR and WPINT. Predictions were compared with a control group's average RSFC (61-85 years, 47% females, 95% right-handed). RESULTS: Three significant patterns emerged: (1) the positive association between WPDUR and RSFC between the medial prefrontal cortex, in the anterior salience network (SN), and bilateral lateral Brodmann area 6, in the visuospatial network (VSN), in participants with more severe chronic pain, resulting in abnormally lower RSFC for shorter WPDUR; (2) the negative association between WPDUR and RSFC between right VSN occipitotemporal cortex (lateral BA37 and visual V5) and bilateral VSN lateral Brodmann area 6, independently of WPINT, resulting in abnormally higher and lower RSFC for shorter and longer WPDUR, respectively; and (3) the positive association between WPDUR and the left hemisphere's salience network-default mode network connectivity (between the hippocampus and both dorsal insula and ventral or opercular BA44), independently of WPINT, resulting in abnormally higher RSFC for longer WPDUR. CONCLUSION: Musculoskeletal effects on brain functional networks of general healthy individuals could accumulate until being observable at older ages. Results invite to examinations of these effects' impact on function and memory.

Impact of Transcranial Direct Current Stimulation and Cognitive Training on Frontal Lobe Neurotransmitter Concentrations.

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.