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.

Associations between physical exercise type, fluid intelligence, executive function, and processing speed in the oldest-old (85 +).

BACKGROUND: While much is known about the effects of physical exercise in adult humans, literature on the oldest-old (≥ 85 years old) is sparse. The present study explored the relationship between self-reported engagement in physical exercise and cognition in the oldest-old. METHODS: The sample included 184 cognitively healthy participants (98 females, MoCA mean score = 24.81) aged 85 to 99 years old (mean = 88.49 years). Participants completed the Community Healthy Activities Model Program for Seniors (CHAMPS) questionnaire and a cognitive battery including NIH-TB, Coding, Symbol Search, Letter Fluency, and Stroop task. Three groups of participants - sedentary (n = 58; MoCA mean score = 24; 36 females; mean age = 89.03), cardio (n = 60; MoCA mean score = 25.08; 29 females; mean age = 88.62), and cardio + strength training (n = 66; MoCA mean score = 25.28; 33 females; mean age = 87.91) - were derived from responses on CHAMPS. RESULTS: Analyses controlled for years of education, NIH-TB Crystallized Composite, and metabolic equivalent of tasks. The cardio + strength training group had the highest cognitive performances overall and scored significantly better on Coding (p < 0.001) and Symbol Search (p < 0.05) compared to the sedentary group. The cardio + strength training group scored significantly better on Symbol Search, Letter Fluency, and Stroop Color-Word compared to the cardio group (p < 0.05). CONCLUSIONS: Our findings suggest self-reported exercise in the oldest-old is linked to better performance on cognitive measures of processing speed and executive functioning, and that there may be a synergistic effect of combining aerobic and resistance training on cognition.

Computerized adaptive test strategies for the matrix reasoning subtest of the Wechsler Adult Intelligence Scale, 4th Edition (WAIS-IV).

OBJECTIVE: Most neuropsychological tests were developed without the benefit of modern psychometric theory. We used item response theory (IRT) methods to determine whether a widely used test - the 26-item Matrix Reasoning subtest of the WAIS-IV - might be used more efficiently if it were administered using computerized adaptive testing (CAT). METHOD: Data on the Matrix Reasoning subtest from 2197 participants enrolled in the National Neuropsychology Network (NNN) were analyzed using a two-parameter logistic (2PL) IRT model. Simulated CAT results were generated to examine optimal short forms using fixed-length CATs of 3, 6, and 12 items and scores were compared to the original full subtest score. CAT models further explored how many items were needed to achieve a selected precision of measurement (standard error ≤ .40). RESULTS: The fixed-length CATs of 3, 6, and 12 items correlated well with full-length test results (with r = .90, .97 and .99, respectively). To achieve a standard error of .40 (approximate reliability = .84) only 3-7 items had to be administered for a large percentage of individuals. CONCLUSIONS: This proof-of-concept investigation suggests that the widely used Matrix Reasoning subtest of the WAIS-IV might be shortened by more than 70% in most examinees while maintaining acceptable measurement precision. If similar savings could be realized in other tests, the accessibility of neuropsychological assessment might be markedly enhanced, and more efficient time use could lead to broader subdomain assessment.

Presurgical microstructural coherence predicts cognitive change for bariatric surgery patients.

OBJECTIVE: This observational study examined the relationship between presurgical white matter microstructural coherence and cognitive change after weight loss. It was hypothesized that higher baseline fractional anisotropy (FA) would predict greater baseline and change cognition. METHODS: A sample of 24 adults (BMI ≥ 35 kg/m2 ) underwent neuropsychological assessment at baseline and 12 weeks after bariatric surgery. A magnetic resonance imaging brain scan was administered at baseline and processed through Tract-Based Spatial Statistics to compute FA in white matter tracts of interest. Composite scores for attention, learning, processing speed, executive function, verbal fluency, working memory, and overall cognition were calculated. RESULTS: As expected, FA in some tracts of interest was significantly (p < 0.05) positively associated with change in cognition. Inverse relationships were observed between baseline FA and presurgical cognition, which may be explained by increased medial and radial diffusivity and preserved axonal diffusivity. Cognition generally improved after surgery; however, relative but clinically nonsignificant deterioration was observed on learning measures. Poorer baseline cognitive performance was associated with greater postsurgical cognitive improvement. CONCLUSIONS: Presurgical microstructural coherence is associated with magnitude of cognitive change after weight loss. An observed reduction in learning suggests that bariatric surgery may lead to negative outcomes in some cognitive domains, at least temporarily.

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.

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).

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.

Baseline Neuroimaging Predicts Decline to Dementia From Amnestic Mild Cognitive Impairment.

Background and Objectives: Prediction of decline to dementia using objective biomarkers in high-risk patients with amnestic mild cognitive impairment (aMCI) has immense utility. Our objective was to use multimodal MRI to (1) determine whether accurate and precise prediction of dementia conversion could be achieved using baseline data alone, and (2) generate a map of the brain regions implicated in longitudinal decline to dementia. Methods: Participants meeting criteria for aMCI at baseline (N = 55) were classified at follow-up as remaining stable/improved in their diagnosis (N = 41) or declined to dementia (N = 14). Baseline T1 structural MRI and resting-state fMRI (rsfMRI) were combined and a semi-supervised support vector machine (SVM) which separated stable participants from those who decline at follow-up with maximal margin. Cross-validated model performance metrics and MRI feature weights were calculated to include the strength of each brain voxel in its ability to distinguish the two groups. Results: Total model accuracy for predicting diagnostic change at follow-up was 92.7% using baseline T1 imaging alone, 83.5% using rsfMRI alone, and 94.5% when combining T1 and rsfMRI modalities. Feature weights that survived the p < 0.01 threshold for separation of the two groups revealed the strongest margin in the combined structural and functional regions underlying the medial temporal lobes in the limbic system. Discussion: An MRI-driven SVM model demonstrates accurate and precise prediction of later dementia conversion in aMCI patients. The multi-modal regions driving this prediction were the strongest in the medial temporal regions of the limbic system, consistent with literature on the progression of Alzheimer's disease.

Associations of alcohol use, HIV infection, and age with brain white matter microstructure.

Heavy drinking and HIV infection are independently associated with damage to the brain's white matter. The purpose of the current study was to investigate whether current alcohol consumption, HIV infection, and associated characteristics were associated with indices of white matter microstructural integrity in people living with HIV (PLWH) and seronegative individuals. PLWH and controls were categorized as non-drinkers, moderate drinkers, or heavy drinkers. White matter fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were assessed using diffusion tensor imaging (DTI). Voxelwise analyses using tract-based spatial statistics were followed by confirmatory region-of-interest (ROI) analyses. Data from 108 participants (62 PLWH, 46 controls) were suitable for analysis. Average age (± standard deviation) was 45.2 ± 11.1 years, and the sample was 42% female. The majority of PLWH were on antiretroviral therapy (94%) and were virally suppressed (69%). PLWH and controls did not differ on substance use. Heavier alcohol intake was significantly associated with lower FA and higher RD in widespread areas. Heavy drinking was significantly associated with higher AD in a small region. The main effect of HIV was not significant, but a significant HIV-age interaction was observed. Follow-up ROI analyses confirmed the main effect of drinking group and HIV-age interaction. In conclusion, results are consistent with a dose-dependent association of alcohol use with lower white matter microstructural coherence. Concordance between FA and RD findings suggests dysmyelination as a mechanism. Findings underscore the need to address unhealthy alcohol use in HIV-positive and seronegative individuals, the consequences of which may be exacerbated by aging.

Reduced Working Memory is Associated with Heavier Alcohol Consumption History, Role Impairment and Executive Function Difficulties.

Both HIV status and heavy alcohol use have been associated with reduced cognitive function, particularly in the domains of working memory and executive function. It is unclear what aspects of working memory and executive function are associated with HIV status and heavy alcohol use and whether performance on these measures are associated with functional impairment. We examined the relationship between HIV, history of heavy alcohol consumption, and HIV/alcohol interaction on speeded tests of frontal inhibitory abilities, a working memory task related to mental manipulation of letters and numbers, cognitive flexibility, and measures of functional impairment. Study participants included 284 individuals (151 HIV +) recruited from two different studies focusing on HIV associated brain dysfunction, one specific to the effects of alcohol, the other specific to the effects of aging. HIV status was not independently associated with working memory and executive function measures. Higher level of alcohol consumption was associated with reduced performance on Letter Number Sequencing. Poorer Letter Number Sequencing performance was associated with role impairment (an inability to do certain kinds of work, housework, or schoolwork) and executive function difficulties. Future studies should examine causal associations and interventions targeting working memory abilities.

RESUMEN: Tanto el estado del VIH como el consumo excesivo de alcohol se han asociado con una función cognitiva reducida, particularmente en los dominios de la memoria de trabajo y la función ejecutiva. No está claro qué aspectos de la memoria de trabajo y la función ejecutiva están asociados con el estado del VIH y el consumo excesivo de alcohol y si el desempeño en estas medidas está asociado con un deterioro funcional. Examinamos la relación entre el VIH, el historial de consumo excesivo de alcohol y la interacción VIH / alcohol, en pruebas aceleradas de capacidades inhibitorias frontales, tareas de memoria de trabajo relacionadas con la manipulación mental de letras y números, flexibilidad cognitiva y medidas de deterioro funcional. Los participantes del estudio incluyeron 284 personas (151 VIH +) reclutadas de dos estudios diferentes que se centran en la disfunción cerebral asociada al VIH, uno específico de los efectos del alcohol y el otro específico de los efectos del envejecimiento. El estado del VIH no se asoció de forma independiente con las medidas de memoria de trabajo y función ejecutiva. Un mayor nivel de consumo de alcohol se asoció con un rendimiento reducido en la secuenciación de números de letras. Un desempeño deficiente en la secuenciación de números de letras se asoció con un deterioro de los roles (una incapacidad para realizar ciertos tipos de trabajo, tareas domésticas o escolares) y dificultades en las funciones ejecutivas. Los estudios futuros deben examinar las asociaciones causales y las intervenciones dirigidas a las capacidades de la memoria de trabajo.

MicroRNA predicts cognitive performance in healthy older adults.

The expression of microRNA (miRNA) is influenced by ongoing biological processes, including aging, and has begun to play a role in the measurement of neurodegenerative processes in central nervous system. The purpose of this study is to utilize machine learning approaches to determine whether miRNA can be utilized as a blood-based biomarker of cognitive aging. A random forest regression combining miRNA with biological (brain volume), clinical (comorbid conditions), and demographic variables in 115 typically aging older adults explained the greatest level of variance in cognitive performance compared to the other machine learning models explored. Three miRNA (miR-140-5p, miR-197-3p, and miR-501-3p) were top-ranked predictors of multiple cognitive outcomes (Fluid, Crystallized, and Overall Cognition) and past studies of these miRNA link them to cellular senescence, inflammatory signals for atherosclerotic formation, and potential development of neurodegenerative disorders (e.g., Alzheimer's disease). Several novel miRNAs were also linked to age and multiple cognitive functions, findings which together warrant further exploration linking these miRNAs to brain-derived metrics of neurodegeneration in typically aging older adults.

The association of white matter free water with cognition in older adults.

BACKGROUND: Extracellular free water within cerebral white matter tissue has been shown to increase with age and pathology, yet the cognitive consequences of free water in typical aging prior to the development of neurodegenerative disease remains unclear. Understanding the contribution of free water to cognitive function in older adults may provide important insight into the neural mechanisms of the cognitive aging process. METHODS: A diffusion-weighted MRI measure of extracellular free water as well as a commonly used diffusion MRI metric (fractional anisotropy) along nine bilateral white matter pathways were examined for their relationship with cognitive function assessed by the NIH Toolbox Cognitive Battery in 47 older adults (mean age â€‹= â€‹74.4 years, SD â€‹= â€‹5.4 years, range â€‹= â€‹65-85 years). Probabilistic tractography at the 99th percentile level of probability (Tracts Constrained by Underlying Anatomy; TRACULA) was utilized to produce the pathways on which microstructural characteristics were overlaid and examined for their contribution to cognitive function independent of age, education, and gender. RESULTS: When examining the 99th percentile probability core white matter pathway derived from TRACULA, poorer fluid cognitive ability was related to higher mean free water values across the angular and cingulum bundles of the cingulate gyrus, as well as the corticospinal tract and the superior longitudinal fasciculus. There was no relationship between cognition and mean FA or free water-adjusted FA across the 99th percentile core white matter pathway. Crystallized cognitive ability was not associated with any of the diffusion measures. When examining cognitive domains comprising the NIH Toolbox Fluid Cognition index relationships with these white matter pathways, mean free water demonstrated strong hemispheric and functional specificity for cognitive performance, whereas mean FA was not related to age or cognition across the 99th percentile pathway. CONCLUSIONS: Extracellular free water within white matter appears to increase with normal aging, and higher values are associated with significantly lower fluid but not crystallized cognitive functions. When using TRACULA to estimate the core of a white matter pathway, a higher degree of free water appears to be highly specific to the pathways associated with memory, working memory, and speeded decision-making performance, whereas no such relationship existed with FA. These data suggest that free water may play an important role in the cognitive aging process, and may serve as a stronger and more specific indicator of early cognitive decline than traditional diffusion MRI measures, such as FA.

History of Alcohol Consumption and HIV Status Related to Functional Connectivity Differences in the Brain During Working Memory Performance.

BACKGROUND: Poorer working memory function has previously been associated with alcohol misuse, Human Immunodeficiency Virus (HIV) positive status, and risky behavior. Poorer working memory performance relates to alterations in specific brain networks. OBJECTIVE: The current study examined if there was a relationship between brain networks involved in working memory and reported level of alcohol consumption during an individual's period of heaviest use. Furthermore, we examined whether HIV status and the interaction between HIV and alcohol consumption was associated with differences in these brain networks. METHODS: Fifty adults, 26 of whom were HIV positive, engaged in an n-back working memory task (0-back and 2-back trials) administered in a magnetic resonance imaging (MRI) scanner. The Kreek- McHugh-Schluger-Kellogg (KMSK) scale of alcohol consumption was used to characterize an individual's period of heaviest use and correlates well with their risk for alcohol dependence. Connectivity analyses were conducted using data collected during n-back task. RESULTS: Functional connectivity differences associated with greater alcohol consumption included negative connectivity, primarily from parietal attention networks to frontal networks. Greater alcohol consumption was also associated with positive connectivity from working memory nodes to the precuneus and paracingulate. HIV positive status was associated with more nodes of negative functional connectivity relative to alcohol consumption history alone, particularly in the frontoparietal networks. The HIV positive individuals with heavier drinking history related to negative fronto-parietal connectivity, along with positive connectivity from working memory nodes to mesolimbic regions. CONCLUSION: Findings allow for a better understanding of brain networks affected by HIV and alcohol and may provide avenues for interventions.

The joint effect of aging and HIV infection on microstructure of white matter bundles.

Recent evidence suggests the aging process is accelerated by HIV. Degradation of white matter (WM) has been independently associated with HIV and healthy aging. Thus, WM may be vulnerable to joint effects of HIV and aging. Diffusion-weighted imaging (DWI) was conducted with HIV-seropositive (n = 72) and HIV-seronegative (n = 34) adults. DWI data underwent tractography, which was parcellated into 18 WM tracts of interest (TOIs). Functional Analysis of Diffusion Tensor Tract Statistics (FADTTS) regression was conducted assessing the joint effect of advanced age and HIV on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) along TOI fibers. In addition to main effects of age and HIV on WM microstructure, the interactive effect of age and HIV was significantly related to lower FA and higher MD, AD, and RD across all TOIs. The location of findings was consistent with the clinical presentation of HIV-associated neurocognitive disorders. While older age is related to poorer WM microstructure, its detrimental effect on WM is stronger among HIV+ relative to HIV- individuals. Loss of WM integrity in the context of advancing age may place HIV+ individuals at increased risk for brain and cognitive compromise.

Neurocognitive Deficits in a Cohort With Class 2 and Class 3 Obesity: Contributions of Type 2 Diabetes and Other Comorbidities.

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.

Relationship of fatigue with cognitive performance in women with early-stage breast cancer over 2 years.

OBJECTIVE: Fatigue and cognitive dysfunction are major concerns for women with early-stage breast cancer during treatment and into survivorship. However, interrelationships of these phenomena and their temporal patterns over time are not well documented, thus limiting the strategies for symptom management interventions. In this study, changes in fatigue across treatment phases and the relationship among fatigue severity and its functional impact with objective cognitive performance were examined. METHODS: Participants (N = 75) were assessed at five time points beginning prior to chemotherapy to 24 months after initial chemotherapy. Fatigue severity and impact were measured on the Brief Fatigue Inventory. Central nervous system (CNS) Vital Signs was used to measure performance based cognitive testing. Temporal changes in fatigue were examined, as well as the relationship between fatigue and cognitive performance, at each time point using linear mixed effect models. RESULTS: Severity of fatigue varied as a function of phase of treatment. Fatigue severity and its functional impact were moderate at baseline, increased significantly during chemotherapy, and returned to near baseline levels by 2 years. At each time point, fatigue severity and impact were significantly associated with diminished processing speed and complex attention performance. CONCLUSIONS: A strong association between fatigue and objective cognitive performance suggests that they are likely functionally related. That cognitive deficits were evident at baseline, whereas fatigue was more chemotherapy dependent, implicates that two symptoms share some common bases but may differ in underlying mechanisms and severity over time. This knowledge provides a basis for introducing strategies for tailored symptom management that vary over time.

Heavy Alcohol Use and Age Effects on HIV-Associated Neurocognitive Function.

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.

Temporal lobe epilepsy affects spatial organization of entorhinal cortex connectivity.

Evidence for structural connectivity patterns within the medial temporal lobe derives primarily from postmortem histological studies. In humans and nonhuman primates, the parahippocampal gyrus (PHg) is subdivided into parahippocampal (PHc) and perirhinal (PRc) cortices, which receive input from distinct cortical networks. Likewise, their efferent projections to the entorhinal cortex (ERc) are distinct. The PHc projects primarily to the medial ERc (M-ERc). The PRc projects primarily to the lateral portion of the ERc (L-ERc). Both M-ERc and L-ERc, via the perforant pathway, project to the dentate gyrus and hippocampal (HC) subfields. Until recently, these neural circuits could not be visualized in vivo. Diffusion tensor imaging algorithms have been developed to segment gray matter structures based on probabilistic connectivity patterns. However, these algorithms have not yet been applied to investigate connectivity in the temporal lobe or changes in connectivity architecture related to disease processes. In this study, this segmentation procedure was used to classify ERc gray matter based on PRc, ERc, and HC connectivity patterns in 7 patients with temporal lobe epilepsy (TLE) without hippocampal sclerosis (mean age, 14.86 ±â€¯3.34 years) and 7 healthy controls (mean age, 23.86 ±â€¯2.97 years). Within samples paired t-tests allowed for comparison of ERc connectivity between epileptogenic and contralateral hemispheres. In healthy controls, there were no significant within-group differences in surface area, volume, or cluster number of ERc connectivity-defined regions (CDR). Likewise, in line with histology results, ERc CDR in the control group were well-organized, uniform, and segregated via PRc/PHc afferent and HC efferent connections. Conversely, in TLE, there were significantly more PRc and HC CDR clusters in the epileptogenic than the contralateral hemisphere. The surface area of the PRc CDR was greater, and that of the HC CDRs was smaller, in the epileptogenic hemisphere as well. Further, there was no clear delineation between M-ERc and L-ERc connectivity with PRc, PHc or HC in TLE. These results suggest a breakdown of the spatial organization of PHg-ERc-HC connectivity in TLE. Whether this breakdown is the cause or result of epileptic activity remains an exciting research question.

The Impact of Alcohol Use on Frontal White Matter in HIV.

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.

Broca's area - thalamic connectivity.

Broca's area is crucially involved in language processing. The sub-regions of Broca's area (pars triangularis, pars opercularis) presumably are connected via corticocortical pathways. However, growing evidence suggests that the thalamus may also be involved in language and share some of the linguistic functions supported by Broca's area. Functional connectivity is thought to be achieved via corticothalamic/thalamocortical white matter pathways. Our study investigates structural connectivity between Broca's area and the thalamus, specifically ventral anterior nucleus and pulvinar. We demonstrate that Broca's area shares direct connections with these thalamic nuclei and suggest a local Broca's area-thalamus network potentially involved in linguistic processing. Thalamic connectivity with Broca's area may serve to selectively recruit cortical regions storing multimodal features of lexical items and to bind them together during lexical-semantic processing. In addition, Broca's area-thalamic circuitry may enable cortico-thalamo-cortical information transfer and modulation between BA 44 and 45 during language comprehension and production.