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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. [ABSTRACT FROM AUTHOR]

Background: Rapid declines in processing speed performance occur in aging and serve as a critical marker of cognitive abilities. Studies suggest that Useful Field of View (UFOV) training may ameliorate cognitive decline. The ACTIVE trial, consisting of over 2,800 participants, found a 29% reduction in ADRD risk 10 years following intervention. Recent clinical trials aimed at slowing cognitive decline in AD have focused on UFOV‐based interventions. Despite its efficacy, little is known about its neural correlates. The current study investigated blood‐oxygen level dependent (BOLD) activation patterns of the UFOV task. Method: 233 older adults completed the UFOV task while undergoing task‐based fMRI. The UFOV task requires participants to identify a central target, as well as a peripheral target amongst distractors, presented for a brief period of time. First‐level contrasts modeled hemodynamic response, while second‐level analyses assessed unique BOLD activation associated with encoding and recall components of the task. Age, education, sex and scanner were included as covariates. Significant clusters were defined as >10 voxels, and all clusters were corrected at a false discovery rate (FDR) of p<0.05. Result: Previous data have shown widespread bilateral whole‐brain activation associated with the encoding component, whereas discrete activation patterns were related to the recall component of the task. Additionally, numerous shared brain regions were critical to both the encoding and recall components of the UFOV task. We further investigated cortical activation patterns associated with age‐related differences in UFOV performance. Variability in performance was related to widespread patterns of activation during the encoding component of the UFOV task, namely the superior parietal lobule, insula, hippocampus and DLPFC. Assessing UFOV performance variability within recall, no significant clusters survived FDR correction. Furthermore, the inferior parietal lobule, cerebellum, and inferior frontal gyrus were critical in both encoding and recall in UFOV performance. Conclusion: The present study elucidates pivotal regions associated with UFOV task performance. Notably, we found that variability in UFOV performance is directly associated with neural activation during the presentation/apprehension of the stimuli, but not during recall. These findings suggest that variation in neural activation during speeded attentional processing is central to age‐related UFOV performance differences, and interventions targeting these neural processes may be of benefit. [ABSTRACT FROM AUTHOR]

Understanding and reducing variability of response to transcranial direct current stimulation (tDCS) requires measuring what factors predetermine sensitivity to tDCS and tracking individual response to tDCS. Human trials, animal models, and computational models suggest structural traits and functional states of neural systems are the major sources of this variance. There are 118 published tDCS studies (up to October 1, 2018) that used fMRI as a proxy measure of neural activation to answer mechanistic, predictive, and localization questions about how brain activity is modulated by tDCS. FMRI can potentially contribute as: a measure of cognitive state‐level variance in baseline brain activation before tDCS; inform the design of stimulation montages that aim to target functional networks during specific tasks; and act as an outcome measure of functional response to tDCS. In this systematic review, we explore methodological parameter space of tDCS integration with fMRI spanning: (a) fMRI timing relative to tDCS (pre, post, concurrent); (b) study design (parallel, crossover); (c) control condition (sham, active control); (d) number of tDCS sessions; (e) number of follow up scans; (f) stimulation dose and combination with task; (g) functional imaging sequence (BOLD, ASL, resting); and (h) additional behavioral (cognitive, clinical) or quantitative (neurophysiological, biomarker) measurements. Existing tDCS‐fMRI literature shows little replication across these permutations; few studies used comparable study designs. Here, we use a representative sample study with both task and resting state fMRI before and after tDCS in a crossover design to discuss methodological confounds. We further outline how computational models of current flow should be combined with imaging data to understand sources of variability. Through the representative sample study, we demonstrate how modeling and imaging methodology can be integrated for individualized analysis. Finally, we discuss the importance of conducting tDCS‐fMRI with stimulation equipment certified as safe to use inside the MR scanner, and of correcting for image artifacts caused by tDCS. tDCS‐fMRI can address important questions on the functional mechanisms of tDCS action (e.g., target engagement) and has the potential to support enhancement of behavioral interventions, provided studies are designed rationally. [ABSTRACT FROM AUTHOR]

Objective: This study examined the relationship between specific metabolic and vascular risk factors and cognition in adults with severe obesity.Methods: A total of 129 adults (with BMI ≥ 35 kg/m2 ) underwent a baseline clinical evaluation and neuropsychological assessment. Regression analyses examined the relationship between cognition and medical factors (BMI, hemoglobin A1c, diabetes, hypertension, continuous positive airway pressure use, obstructive sleep apnea [OSA], and osteoarthritis).Results: Diabetes was associated with deficits in overall cognitive performance and with deficits in the executive processing speed and verbal fluency domains. Hemoglobin A1c was inversely related to overall cognitive performance and deficits in the attention domain. Participants using continuous positive airway pressure to treat OSA had stronger learning and memory performance, whereas OSA was associated with reduced total learning. Elevated BMI together with diabetes diagnosis was associated with reduced verbal fluency and greater variability in sustained attention.Conclusions: Obesity-associated comorbidities most notably appeared to have a greater relative influence on cognitive performance than BMI itself in adults with severe obesity. This likely reflects the fact that a very elevated BMI was ubiquitous and thereby probably exerted a similar influence among all adults in the cohort. Accordingly, in the context of severe obesity, diabetes and other comorbidities may have greater sensitivity to cognitive deficits than BMI alone. [ABSTRACT FROM AUTHOR]

OBJECTIVES To evaluate the effect of hospitalizations on patterns of sedentary and physical activity time in mobility‐limited older adults randomized to structured physical activity or health education. DESIGN Secondary analysis of investigator‐blinded, parallel‐group, randomized trial conducted at 8 U.S. centers between February 2010 and December 2013. PARTICIPANTS Sedentary men and women aged 70 to 89 at baseline who wore a hip‐fitted accelerometer 7 consecutive days at baseline and 6, 12, and 24 months after randomization (N=1,341). MEASUREMENTS Participants were randomized to a physical activity (PA; n = 669) intervention that included aerobic, resistance, and flexibility training or to a health education (HE; n = 672) intervention that consisted of workshops on older adult health and light upper‐extremity stretching. Accelerometer patterns were characterized as bouts of sedentary (<100 counts/min; ≥1, ≥10, ≥30, ≥60 minute lengths) and activity (≥100 counts/min; ≥1, ≥2, ≥5, ≥10 minute lengths) time. Each participant was categorized as having 0, 1 to 3, or 4 or more cumulative hospital days before each accelerometer assessment. RESULTS: Hospitalization increased sedentary time similarly in both intervention groups (8 min/d for 1–3 cumulative hospital days and 16 min/d for ≥4 cumulative hospital days). Hospitalization was also associated with less physical activity time across all bouts of less than 10 minutes (≥1: −7 min/d for 1–3 cumulative hospital days, –16 min/d for ≥4 cumulative hospital days; ≥2: −5 min/d for 1–3 cumulative hospital days, −11 min/d for ≥4 cumulative hospital days; ≥5: −3 min/d for 1–3 cumulative hospital days, −4 min/d for ≥4 cumulative hospital days). There was no evidence of recovery to prehospitalization levels (time effect p >.41). PA participants had less sedentary time in bouts of less than 30 minutes than HE participants (−8 to −10 min/d) and more total activity (+3 to +6 min/d), although hospital‐related changes were similar between the intervention groups (interaction effect p >.26). CONCLUSION: Participating in a PA intervention before hospitalization had expected benefits, but participants remained susceptible to hospitalization's detrimental effects on their daily activity levels. There was no evidence of better activity recovery after hospitalization. J Am Geriatr Soc 67:261–268, 2019. [ABSTRACT FROM AUTHOR]

Background: There is growing concern about the health impact of heavy alcohol use in people infected with human immunodeficiency virus (HIV+). Mixed findings of past studies regarding the cognitive impact of alcohol use in HIV+ adults have been mixed, with inconsistent evidence that alcohol consumption exacerbates HIV‐associated brain dysfunction. This study examined contributions of current heavy drinking, lifetime alcohol use disorder (AUD), and age to cognitive deficits in HIV+ adults, and relative to other HIV‐associated clinical factors. Methods: Cognitive performance of HIV+ adults (n = 104) was assessed, and comparisons were made between heavy current to nonheavy drinkers (NIAAA criteria), lifetime AUD versus no‐AUD, and older (>50 years) versus younger participants. Hierarchical regression analyses were conducted to examine the association between cognitive performance and current heavy drinking, lifetime AUD, and older age, while also correcting for HIV clinical factors and history of other substance use. Results: Individuals reporting current heavy drinking and meeting criteria for lifetime AUD demonstrated the greatest degree of deficits across multiple cognitive domains. Deficits were greatest among HIV+ adults with lifetime AUD, and older age was also associated with weaker cognitive performance. Lifetime AUD and older age independently exhibited stronger associations with cognitive performance than HIV clinical factors (e.g., viral load, current CD4, and nadir CD4) or past opiate and cocaine use. Conclusions: Current heavy drinking and lifetime AUD adversely affect cognitive function in HIV+ adults. Greatest deficits existed when there was a history of AUD and continued current heavy drinking, indicating that past AUD continues to have an adverse impact and should not be ignored. That alcohol use was more strongly associated with cognitive performance than HIV clinical factors underscore clinical importance of targeting reduction in heavy alcohol consumption in HIV+ adults. [ABSTRACT FROM AUTHOR]

Background: Alcohol use disorder (AUD) is prevalent among individuals diagnosed with human immunodeficiency virus (HIV), and both HIV and alcohol use have been shown to negatively affect the integrity of white matter pathways in the brain. Behavioral, functional, and anatomical impairments have been linked independently to HIV and alcohol use, and these impairments have bases in specific frontally mediated pathways within the brain. Methods: Magnetic resonance imaging data were acquired for 37 HIV+ participants without dementia or hepatitis C. Imaging data were processed through the FreeSurfer and TraCULA pipelines to obtain 4 bilateral frontal white matter tracts for each participant. Diffusion metrics of white matter integrity along the highest probability pathway for each tract were analyzed with respect to demographics, disease‐specific variables, and reported substance use. Results: Significantly increased axial diffusivity (decreased axonal integrity) and a trending increase in mean diffusivity were observed along the anterior thalamic radiation (ATR) in participants with a history of AUD. A diagnosis of AUD explained over 36% of the variance in diffusivity along the ATR overall when accounting for clinical variables including nadir CD4 and age‐adjusted HIV infection length. Conclusions: This study provides evidence of HIV‐related associations between alcohol use and indicators of axonal integrity loss along the ATR, a frontal pathway involved in the inhibition of addictive or unwanted behaviors. Reduced axonal integrity of this pathway was greatest in HIV+ participants with an AUD, even when considering the effect of age‐adjusted disease length and severity (nadir CD4). This finding implicates a potential biological mechanism linking reduced integrity of frontal white matter to the high prevalence of AUD in an HIV+ population without dementia or hepatitis C. [ABSTRACT FROM AUTHOR]

Background: Effective non‐pharmacological interventions to remediate age‐related cognitive decline and alter trajectories toward dementia are limited. The Augmenting Cognitive Training in Older Adults trial (ACT) was the first phase III randomized clinical trial initiated for transcranial direct current stimulation. Method: This NIA funded trial sought to evaluate whether 3 months of cognitive training paired with bilateral 2mA tDCS to the frontal lobes could produce clinically meaningful improvement in a composite measure of cognitive function in healthy older adults: the NIH Toolbox Fluid Cognition Composite score. The ACT trial will be unblinded April 30, 2022. Further still, over the past 5 years, it has become increasingly evident that fixed dosing approaches to tDCS, like those used in the ACT and every other trial to date, are insufficient for addressing individual differences and maximizing clinical outcomes. Results: We will present, for the first time, the primary outcome results from the ACT trial. In addition, we will present initial findings from related secondary neuroimaging and cognitive indices. In this talk, we will also present preliminary findings from our ongoing work to refine dosing technology for tDCS in older adults using computational modeling, artificial intelligence and multimodal imaging, paired with tDCS outcomes from the ACT trial. Conclusion: We will present new analyses, available only upon unblinding of ACT. These data use person‐specific computational models of tDCS current flow paired with machine learning and clinical outcomes to identify critical characteristics of tDCS current in the brain (e.g., intensity, direction of current flow) most strongly associated with response vs. non‐response. These data will provide initial insight into which regions of the brain and what characteristics of current were strongly associated with treatment response in the ACT trial. In addition, these data also provide critical insight into how stimulation dosing (electrode positioning, stimulation intensity) can be modified at a person‐specific level to potentially enhance clinical outcomes. Thus, the proposed talk will provide state of the art trial findings from the first completed tDCS Phase III clinical trial paired with next generation approaches to remediated age‐related cognitive decline using tDCS technology. [ABSTRACT FROM AUTHOR]

Background The acute consumption of excessive quantities of alcohol causes well-recognized neurophysiological and cognitive alterations. As people reach advanced age, they are more prone to cognitive decline. To date, the interaction of current heavy alcohol (ethanol [ EtOH]) consumption and aging remains unclear. This study tested the hypothesis that negative consequences of current heavy alcohol consumption on neurocognitive function are worse with advanced age. Further, we evaluated the relations between lifetime history of alcohol dependence and neurocognitive function Methods Sixty-six participants underwent a comprehensive neurocognitive battery. Current heavy EtOH drinkers were classified using National Institute on Alcohol Abuse and Alcoholism criteria (EtOH heavy, n = 21) based on the Timeline follow-back and a structured clinical interview and compared to nondrinkers, and moderate drinkers (EtOH low, n = 45). Of the total population, 53.3% had a lifetime history of alcohol dependence. Neurocognitive data were grouped and analyzed relative to global and domain scores assessing: global cognitive function, attention/executive function, learning, memory, motor function, verbal function, and speed of processing. Results Heavy current EtOH consumption in older adults was associated with poorer global cognitive function, learning, memory, and motor function ( ps < 0.05). Furthermore, lifetime history of alcohol dependence was associated with poorer function in the same neurocognitive domains, in addition to the attention/executive domain, irrespective of age ( ps < 0.05). Conclusions These data suggest that while heavy current alcohol consumption is associated with significant impairment in a number of neurocognitive domains, history of alcohol dependence, even in the absence of heavy current alcohol use, is associated with lasting negative consequences for neurocognitive function. [ABSTRACT FROM AUTHOR]

Objective: Structural neuroimaging studies in older adults have consistently shown volume reductions in both major and subthreshold depression. Cortical thickness, another measure of brain structure, has not been well studied in this population. We examined cortical thickness in older adults across a range of depressive symptom (DS) severity.Methods: Forty-three community-dwelling older adults (mean age = 68.80 ± 7.00 years) underwent magnetic resonance imaging. Based on a priori hypotheses, we examined cortical thickness in regions of interest in the rostral anterior cingulate, orbitofrontal cortex, middle frontal gyrus, and isthmus cingulate using multiple linear regressions with depression questionnaire scores as the independent variable and age, sex, and mean hemispheric thickness as covariates. We also performed an exploratory vertex-wise analysis.Results: After correction for multiple comparisons, we found an association between increased DSs and greater cortical thickness in the right isthmus cingulate (F(1, 38) = 8.09, false discovery rate corrected p = 0.028; R(2) = 35.78) in the region of interest analysis and in the left precuneus (cluster size = 413, p = 0.00002) in the vertex-wise analysis.Conclusions: Older adults with higher DSs also have greater cortical thickness in the isthmus cingulate and precuneus, areas important for emotion regulation and self-referential processing. Additional research is needed to elucidate the mechanisms and potential clinical significance underlying this relationship. [ABSTRACT FROM AUTHOR]

Background: The Useful Field of View (UFOV) test assesses divided attention/speed of processing and relates to independent activities of daily living. Cognitive training utilizing UFOV improves speed‐of‐processing and reduces dementia risk by 29%. Neural correlates of UFOV include key regions of “higher‐order” resting state networks (RSNs) involved in attention processing and dementia risk: Frontoparietal control network (FPCN), Cingulo Opercular network (CON), Default Mode network (DMN), and Dorsal Attention network (DAN). Reduced anti‐correlation between the DMN and task positive RSNs (FPCN, CON, and DAN) is reported in dementia progression. Assessing the relationship of UFOV performance with within‐ and between‐ RSN connectivity may suggest neural mechanisms of cognitive training and potential pathways for reduced dementia risk. We hypothesize that FPCN, CON, and DAN within network connectivity will predict UFOV performance, as these networks are involved in attention processing. We also predict that DMN‐CON anti‐correlation will predict UFOV performance, as this anti‐correlation is related to dementia progression. Method: 279 healthy older adults (M = 71.6, SD = 5.1) from a larger multi‐site clinical trial were recruited. UFOV performance was measured via Double Decision (DD) task from Posit Science Brain HQ. Participants correctly identified a central target, while simultaneously specifying location of a peripheral target among distractors. Average within‐network connectivity of FPCN, CON, DAN, and DMN, and between‐network connectivity of DMN‐CON, DMN‐FPCN, and DMN‐DAN were extracted from resting‐state functional magnetic resonance imaging through the CONN Toolbox v18b via SPM 12. Multiple linear regressions predicted DD performance from within‐ and between‐network values, controlling for age, sex, education, and scanner. All between‐network values were included in the same regression model. Result: Reduced CON (β=‐.134, p=.023) and FPCN (β=‐.126, p=.029) connectivity was associated with poorer DD performance. Less DMN‐CON anticorrelation demonstrated a trend for predicting better DD performance (β=‐.126, p=.060). Conclusion: Consistent with previous research, faster DD performance is associated with RSNs involved in executive functioning, attention, and processing speed. Although only trending, reduced DMN‐CON anticorrelation may be related to DD performance. This suggests that within network connectivity may contribute more to DD performance than between‐network connectivity involved in dementia progression in healthy older adults. [ABSTRACT FROM AUTHOR]

Objective: To establish feasibility for the hypothesis that patients in acute rehabilitation who are hospitalized for disorders not known to involve cerebral injury can have significant cognitive impairment. Design: A comparison of performances on neuropsychological tests between 2 samples of subjects: inpatients in an acute rehabilitation hospital without known cerebral disease and normal community-dwelling persons. Setting: Acute inpatient rehabilitation hospital. Patients and Participants: Nineteen hospitalized patients without delirium who were screened for pre-existing cerebral and psychiatric illness, dementia, and dependency in basic self-care skills before hospitalization. Eighteen community-dwelling persons who were not different in terms of age and education served as the control group. Methods: Participants completed 10 commonly used neuropsychological tests of executive, language, and memory functions. Data were analyzed by using multivariate analysis of variance. Main Outcome Measurements: Raw scores on the 10 neuropsychological tests. Results: Hospitalized patients performed significantly worse on 9 of 10 tests than community-dwelling participants. Older hospitalized participants had significantly greater cognitive impairment than younger hospitalized participants, which suggested increased susceptibility to effects of hospitalization on cognition. Conclusions: Patients hospitalized without brain injury, and especially elderly patients, should be carefully monitored for cognitive deficits that may affect posthospitalization quality of living. Further research is needed to determine whether the cognitive deficits in such patients persist after discharge and affect functional independence, and to identify mechanisms for the deficits. Furthermore, the use of hospitalized participants without brain injury as control subjects in neuropsychological studies of brain injury should be balanced with an additional comparison group of matched, neurologically healthy, normal subjects who live in the community to control for cognitive impairments that are associated with acute hospitalization. [Copyright &y& Elsevier]

Aim Major depression is associated with hippocampal volume changes, especially in late-life depression. These changes usually consist of volume reductions, but depression-related increases in hippocampal volume have also been reported. Subfield analysis has identified structural changes primarily in the cornu ammonis (CA) 1, CA2-3 and subiculum of the hippocampus in individuals with major depression; however, it is unclear whether lower levels of depressive symptoms are also associated volume reduction, or if depressive symptoms interact with age to impact hippocampal subfields. The current study addressed these questions. Methods A total of 43 community-dwelling older adults completed the Center for Epidemiologic Studies Depression Scale and underwent magnetic resonance imaging. Hippocampal subfield segmentation was carried out using an automated procedure, and left and right volumes from CA1, CA2-3, and the subiculum served as outcome measures. Multiple hierarchical regressions were carried out with age, Center for Epidemiologic Studies Depression Scale scores and their interaction as the independent variables, and sex and total intracranial volume as covariates. Results Higher Center for Epidemiologic Studies Depression Scale scores were associated with less age-related volumetric decreases in the right subiculum and right CA1. Conclusions Age-related atrophy in the hippocampus might be counteracted by depressive symptom-related enlargement of CA1 and the subiculum. More research is required to better understand the functional significance of this relationship. Geriatr Gerontol Int 2017; 17: 1494-1500. [ABSTRACT FROM AUTHOR]