Serum albumin and white matter hyperintensities.

People living with HIV and those diagnosed with alcohol use disorders (AUD) relative to healthy individuals commonly have low levels of serum albumin, substantiated as an independent predictor of cardiovascular events. White matter hyperintensities (WMH)-a neuroimaging feature of cerebral small vessel disease-are also related to cardiovascular disease. Despite consensus regarding associations between high levels of urine albumin and WMH prevalence, and low serum albumin levels and impaired cognitive functioning, relations between serum albumin and WMH burdens have rarely been evaluated. Here, a sample including 160 individuals with AUD, 142 living with HIV, and 102 healthy controls was used to test the hypothesis that serum albumin would be inversely related to WMH volumes and directly related to cognitive performance in the two diagnostic groups. Although serum albumin and periventricular WMH volumes showed an inverse relationship in both AUD and HIV groups, this relationship persisted only in the HIV group after consideration of traditional cardiovascular (i.e., age, sex, body mass index (BMI), nicotine use, hypertension, diabetes), study-relevant (i.e., race, socioeconomic status, hepatitis C virus status), and disease-specific (i.e., CD4 nadir, HIV viral load, HIV duration) factors. Further, serum albumin contributed more significantly than periventricular WMH volume to variance in performance on a verbal learning and memory composite score in the HIV group only. Relations in both HIV and AUD groups between albumin and hematological red blood cell markers (e.g., hemoglobin, hematocrit) suggest that in this sample, serum albumin reflects hematological abnormalities. Albumin, a simple serum biomarker available in most clinical settings, may therefore help identify periventricular WMH burden and performance levels in specific cognitive domains in people living with HIV. Whether serum albumin contributes mechanistically to periventricular WMH in HIV will require additional investigation.

Alcohol Use Disorder and Dementia: A Review.

PURPOSE: By 2040, 21.6% of Americans will be over age 65, and the population of those older than age 85 is estimated to reach 14.4 million. Although not causative, older age is a risk factor for dementia: every 5 years beyond age 65, the risk doubles; approximately one-third of those older than age 85 are diagnosed with dementia. As current alcohol consumption among older adults is significantly higher compared to previous generations, a pressing question is whether drinking alcohol increases the risk for Alzheimer's disease or other forms of dementia. SEARCH METHODS: Databases explored included PubMed, Web of Science, and ScienceDirect. To accomplish this narrative review on the effects of alcohol consumption on dementia risk, the literature covered included clinical diagnoses, epidemiology, neuropsychology, postmortem pathology, neuroimaging and other biomarkers, and translational studies. Searches conducted between January 12 and August 1, 2023, included the following terms and combinations: "aging," "alcoholism," "alcohol use disorder (AUD)," "brain," "CNS," "dementia," "Wernicke," "Korsakoff," "Alzheimer," "vascular," "frontotemporal," "Lewy body," "clinical," "diagnosis," "epidemiology," "pathology," "autopsy," "postmortem," "histology," "cognitive," "motor," "neuropsychological," "magnetic resonance," "imaging," "PET," "ligand," "degeneration," "atrophy," "translational," "rodent," "rat," "mouse," "model," "amyloid," "neurofibrillary tangles," "α-synuclein," or "presenilin." When relevant, "species" (i.e., "humans" or "other animals") was selected as an additional filter. Review articles were avoided when possible. SEARCH RESULTS: The two terms "alcoholism" and "aging" retrieved about 1,350 papers; adding phrases-for example, "postmortem" or "magnetic resonance"-limited the number to fewer than 100 papers. Using the traditional term, "alcoholism" with "dementia" resulted in 876 citations, but using the currently accepted term "alcohol use disorder (AUD)" with "dementia" produced only 87 papers. Similarly, whereas the terms "Alzheimer's" and "alcoholism" yielded 318 results, "Alzheimer's" and "alcohol use disorder (AUD)" returned only 40 citations. As pertinent postmortem pathology papers were published in the 1950s and recent animal models of Alzheimer's disease were created in the early 2000s, articles referenced span the years 1957 to 2024. In total, more than 5,000 articles were considered; about 400 are herein referenced. DISCUSSION AND CONCLUSIONS: Chronic alcohol misuse accelerates brain aging and contributes to cognitive impairments, including those in the mnemonic domain. The consensus among studies from multiple disciplines, however, is that alcohol misuse can increase the risk for dementia, but not necessarily Alzheimer's disease. Key issues to consider include the reversibility of brain damage following abstinence from chronic alcohol misuse compared to the degenerative and progressive course of Alzheimer's disease, and the characteristic presence of protein inclusions in the brains of people with Alzheimer's disease, which are absent in the brains of those with AUD.

Race explains substantial variance in whole blood thiamine diphosphate concentrations.

Deficiency for thiamine (vitamin B1), traditionally assessed via the activity of the thiamine-dependent enzyme erythrocyte transketolase, has been reported in individuals with alcohol use disorder (AUD) and in people with HIV; concentrations of the metabolically active diphosphate form, however, have yet to be reported in HIV cohorts and results in AUD are equivocal. In this cross-sectional study, samples from 170 AUD, 130 HIV, and 100 healthy control individuals were analyzed to test the hypothesis that AUD and HIV groups relative to healthy controls would show low whole blood thiamine diphosphate (TDP) concentrations related to peripheral neuropathy. TDP concentrations were not different in the 3 study groups (P = .6141) but were lower in Black (n = 172) relative to White (n = 155) individuals (P < .0001) regardless of group. In a multiple regression, race relative to diagnoses explained more than 10 times the variance in whole blood TDP concentrations (F4,395 = 3.5, P = .0086; r2 = 15.1]. Performance on a measure of peripheral neuropathy (2-point discrimination) was worse in the HIV and AUD cohorts relative to the healthy control group (P < .0001) but was not associated with TDP concentrations. These findings suggest that Black individuals carry a heightened vulnerability for low whole blood TDP concentrations, but the clinical significance and mechanisms underlying these results remain to be determined.

Contributions of Cerebral White Matter Hyperintensities to Postural Instability in Aging With and Without Alcohol Use Disorder.

BACKGROUND: Both postural instability and brain white matter hyperintensities (WMHs) are noted markers of normal aging and alcohol use disorder (AUD). Here, we questioned what variables contribute to the sway path-WMH relationship in individuals with AUD and healthy control participants. METHODS: The data comprised 404 balance platform sessions, yielding sway path length and magnetic resonance imaging data acquired cross-sectionally or longitudinally in 102 control participants and 158 participants with AUD ages 25 to 80 years. Balance sessions were typically conducted on the same day as magnetic resonance imaging fluid-attenuated inversion recovery acquisitions, permitting WMH volume quantification. Factors considered in multiple regression analyses as potential contributors to the relationship between WMH volumes and postural instability were age, sex, socioeconomic status, education, pedal 2-point discrimination, systolic and diastolic blood pressure, body mass index, depressive symptoms, total alcohol consumed in the past year, and race. RESULTS: Initial analysis identified diagnosis, age, sex, and race as significant contributors to observed sway path-WMH relationships. Inclusion of these factors as predictors in multiple regression analyses substantially attenuated the sway path-WMH relationships in both AUD and healthy control groups. Women, irrespective of diagnosis or race, had shorter sway paths than men. Black participants, irrespective of diagnosis or sex, had shorter sway paths than non-Black participants despite having modestly larger WMH volumes than non-Black participants, which is possibly a reflection of the younger age of the Black sample. CONCLUSIONS: Longer sway paths were related to larger WMH volumes in healthy men and women with and without AUD. Critically, however, age almost fully accounted for these associations.

Contributions of cerebral white matter hyperintensities, age, and pedal perception to postural sway in people with HIV.

OBJECTIVE: With aging, people with HIV (PWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables. DESIGN: Mixed cross-sectional/longitudinal data were acquired over 15 years in 141 PWH and 102 age-range matched controls, 25-80 years old. METHODS: Multimodal structural MRI data were quantified for seven total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and nonpath data on sway path-WMH relations. RESULTS: In simple correlations, longer sway paths were associated with larger WMH volumes in PWH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and two-point pedal discrimination. Although the sway-WMH relations in PWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for five of the seven regions in the eyes-open condition. CONCLUSION: The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for the use of T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3 T and 7 T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI.

Robust thalamic nuclei segmentation from T1-weighted MRI using polynomial intensity transformation.

Accurate segmentation of thalamic nuclei, crucial for understanding their role in healthy cognition and in pathologies, is challenging to achieve on standard T1-weighted (T1w) magnetic resonance imaging (MRI) due to poor image contrast. White-matter-nulled (WMn) MRI sequences improve intrathalamic contrast but are not part of clinical protocols or extant databases. In this study, we introduce histogram-based polynomial synthesis (HIPS), a fast preprocessing transform step that synthesizes WMn-like image contrast from standard T1w MRI using a polynomial approximation for intensity transformation. HIPS was incorporated into THalamus Optimized Multi-Atlas Segmentation (THOMAS) pipeline, a method developed and optimized for WMn MRI. HIPS-THOMAS was compared to a convolutional neural network (CNN)-based segmentation method and THOMAS modified for T1w images (T1w-THOMAS). The robustness and accuracy of the three methods were tested across different image contrasts (MPRAGE, SPGR, and MP2RAGE), scanner manufacturers (PHILIPS, GE, and Siemens), and field strengths (3T and 7T). HIPS-transformed images improved intra-thalamic contrast and thalamic boundaries, and HIPS-THOMAS yielded significantly higher mean Dice coefficients and reduced volume errors compared to both the CNN method and T1w-THOMAS. Finally, all three methods were compared using the frequently travelling human phantom MRI dataset for inter- and intra-scanner variability, with HIPS displaying the least inter-scanner variability and performing comparably with T1w-THOMAS for intra-scanner variability. In conclusion, our findings highlight the efficacy and robustness of HIPS in enhancing thalamic nuclei segmentation from standard T1w MRI.

Age-Accelerated Increase of White Matter Hyperintensity Volumes Is Exacerbated by Heavy Alcohol Use in People Living With HIV.

BACKGROUND: Antiretroviral treatment has enabled people living with HIV infection to have a near-normal life span. With longevity comes opportunities for engaging in risky behavior, including initiation of excessive drinking. Given that both HIV infection and alcohol use disorder (AUD) can disrupt brain white matter integrity, we questioned whether HIV infection, even if successfully treated, or AUD alone results in signs of accelerated white matter aging and whether HIV+AUD comorbidity further accelerates brain aging. METHODS: Longitudinal magnetic resonance imaging-FLAIR data were acquired over a 15-year period from 179 control individuals, 204 participants with AUD, 70 participants with HIV, and 75 participants with comorbid HIV+AUD. White matter hyperintensity (WMH) volumes were quantified and localized, and their functional relevance was examined with cognitive and motor testing. RESULTS: The 3 diagnostic groups each had larger WMH volumes than the control group. Although all 4 groups exhibited accelerating volume increases with aging, only the HIV groups showed faster WMH enlargement than control individuals; the comorbid group showed faster acceleration than the HIV-only group. Sex and HIV infection length, but not viral suppression status, moderated acceleration. Correlations emerged between WMH volumes and attention/working memory and executive function scores of the AUD and HIV groups and between WMH volumes and motor skills in the 3 diagnostic groups. CONCLUSIONS: Even treated HIV can show accelerated aging, possibly from treatment sequelae or legacy effects, and notably from AUD comorbidity. WMH volumes may be especially relevant for tracking HIV and AUD brain health because each condition is associated with liability for hypertensive processes, for which WMHs are considered a marker.

Poor subjective sleep reported by people living with HIV is associated with impaired working memory.

Poor sleep can undermine health and may be especially disruptive to those with chronic conditions including HIV infection. Here, clinically well-described people living with HIV [PLWH] (74 men, 35 women) and healthy control (38 men, 35 women) participants were administered the Pittsburgh Sleep Quality Index (PSQI), a validated measure of subjective sleep with a global score ≥5 able to distinguish good from poor sleepers. In addition, participants completed a battery of neuropsychological tests. PLWH (6.8 ± 3.7) had higher global PSQI scores than healthy controls (4.1 ± 2.8): 39.7 % of uninfected controls and 68.8 % of PLWH had a PSQI≥5 indicative of poor sleep. There were no relations between the global PSQI score and any evaluated variables among uninfected individuals or with demographic or HIV-related variables in PLWH. Instead, a higher global PSQI score among PLWH was associated with worse "Quality of Life" scores [Global Assessment of Functioning (GAF, p=0.0007), Medical Outcomes Study survey (21-item short form, SF-21, p<0.0001), and Activities of Daily Living-Instrumental (ADL-I, p=0.0041)] and higher Beck Depression Index (BDI, p<0.0001) depressive symptoms. Further, in PLWH, higher global PSQI scores were associated with poor performance on a working memory task, the digit backward span (p=0.0036). In PLWH, the 5 variables together explained 32.3 % of the global PSQI score variance; only 3 variables - the SF-21, BDI, and digit backward scores - explained 30.6 % of the variance. To the extent that poor subjective sleep contributes to impaired working memory in HIV, we speculate that this impairment may be ameliorated by improved sleep health.

White matter microstructural integrity continues to develop from adolescence to young adulthood in mice and humans: Same phenotype, different mechanism.

As direct evaluation of a mouse model of human neurodevelopment, adolescent and young adult mice and humans underwent MR diffusion tensor imaging to quantify age-related differences in microstructural integrity of brain white matter fibers. Fractional anisotropy (FA) was greater in older than younger mice and humans. Despite the cross-species commonality, the underlying developmental mechanism differed: whereas evidence for greater axonal extension contributed to higher FA in older mice, evidence for continuing myelination contributed to higher FA in human adolescent development. These differences occurred in the context of species distinctions in overall brain growth: whereas the continued growth of the brain and skull in the murine model can accommodate volume expansion into adulthood, human white matter volume and myelination continue growth into adulthood within a fixed intracranial volume. Appreciation of the similarities and differences in developmental mechanism can enhance the utility of animal models of brain white matter structure, function, and response to exogenous manipulation.

Influence of childhood trauma, HIV infection, alcohol use disorder, and resilience on health-related quality of life in adulthood.

Experience of childhood trauma, especially physical, emotional, and sexual abuse, carries a risk for developing alcohol use disorder (AUD) and engaging in risky behaviors that can result in HIV infection. AUD and HIV are associated with compromised self-reported health-related quality of life (HRQoL) possibly intersecting with childhood trauma. To determine whether poor HRQoL is heightened by AUD, HIV, their comorbidity (AUD + HIV), number of trauma events, or poor resilience, 108 AUD, 45 HIV, 52 AUD + HIV, and 67 controls completed the SF-21 HRQoL, Brief Resilience Scale (BRS), Ego Resiliency Scale (ER-89), and an interview about childhood trauma. Of the 272 participants, 116 reported a trauma history before age 18. Participants had a blood draw, AUDIT questionnaire, and interview about lifetime alcohol consumption. AUD, HIV, and AUD + HIV had lower scores on HRQoL and resilience composite comprising the BRS and ER-89 than controls. Greater resilience was a significant predictor of better quality of life in all groups. HRQoL was differentially moderated in AUD and HIV: more childhood traumas predicted poorer quality of life in AUD and controls, whereas higher T-lymphocyte count contributed to better quality of life in HIV. This study is novel in revealing a detrimental impact on HRQoL from AUD, HIV, and their comorbidity, with differential negative contribution from trauma and beneficial effect of resilience to quality of life. Channeling positive effects of resilience and reducing the incidence and negative impact of childhood trauma may have beneficial effects on health-related quality of life in adulthood independent of diagnosis.

Serum biomarkers of liver fibrosis identify globus pallidus vulnerability.

The CNS manifestation of chronic liver disease can include magnetic resonance (MR) signal hyperintensities in basal ganglia structures. Here, relations between liver (serum-derived fibrosis scores) and brain (regional T1-weighted signal intensities and volumes) integrity were evaluated in a sample of 457 individuals including those with alcohol use disorders (AUD), people living with human immunodeficiency virus (HIV), those comorbid for AUD and HIV, and healthy controls. Liver fibrosis was identified from cutoff scores as follows: aspartate aminotransferase to platelet ratio index (APRI) > 0.7 in 9.4% (n = 43) of the cohort; fibrosis score (FIB4) > 1.5 in 28.0% (n = 128) of the cohort; and non-alcoholic fatty liver disease fibrosis score (NFS) > -1.4 in 30.2% (n = 138) of the cohort. Presence of serum-derived liver fibrosis was associated with high signal intensities selective to basal ganglia (i.e., caudate, putamen, and pallidum) structures. High signal intensities in the pallidum, however, explained a significant portion of the variance in APRI (25.0%) and FIB4 (23.6%) cutoff scores. Further, among the regions evaluated, only the globus pallidus showed a correlation between greater signal intensity and smaller volume (r = -0.44, p <.0001). Finally, higher pallidal signal intensity correlated worse ataxia (eyes open ρ = -0.23, p =.0002; eyes closed ρ = -0.21, p =.0005). This study suggests that clinically relevant serum biomarkers of liver fibrosis such as the APRI may identify individuals vulnerable to globus pallidus pathology and contribute to problems with postural balance.

Postural instability in HIV infection: relation to central and peripheral nervous system markers.

OBJECTIVES: Determine the independent contributions of central nervous system (CNS) and peripheral nervous system (PNS) metrics to balance instability in people with HIV (PWH) compared with people without HIV (PWoH). METHODS: Volumetric MRI (CNS) and two-point pedal discrimination (PNS) were tested as substrates of stance instability measured with balance platform posturography. DESIGN: 125 PWH and 88 PWoH underwent balance testing and brain MRI. RESULTS: The PWH exhibited stability deficits that were disproportionately greater with eyes closed than eyes open compared with PWoH. Further analyses revealed that greater postural imbalance measured as longer sway paths correlated with smaller cortical and cerebellar lobular brain volumes known to serve sensory integration; identified brain/sway path relations endured after accounting for contributions from physiological and disease factors as potential moderators; and multiple regression identified PNS and CNS metrics as independent predictors of postural instability in PWH that differed with the use of visual information to stabilize balance. With eyes closed, temporal volumes and two-point pedal discrimination were significant independent predictors of sway; with eyes open, occipital volume was an additional predictor of sway. These relations were selective to PWH and were not detected in PWoH. CONCLUSION: CNS and PNS factors were independent contributors to postural instability in PWH. Recognizing that myriad inputs must be detected by peripheral systems and brain networks to integrate sensory and musculoskeletal information for maintenance of postural stability, age- or disease-related degradation of either or both nervous systems may contribute to imbalance and liability for falls.

Multi-atlas thalamic nuclei segmentation on standard T1-weighed MRI with application to normal aging.

Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.

Alcohol's effects on the mouse brain are modulated by age and sex.

Binge alcohol consumption is common among adolescents and may impair normal brain development. Emerging, longitudinal studies in adolescents suggest that the effects of binge alcohol exposure on brain structure differ between sexes. To test the hypothesis that the effects of binge alcohol exposure on developmental brain growth trajectories are influenced by age of exposure and sex, adolescent and adult, male and female C57Bl/6 mice (n = 32), were exposed to a binge-like ethanol (EtOH) exposure paradigm (i.e., 5 cycles of 2 on/2 off days of 5 g/kg EtOH intraperitoneal) or served as saline controls. Longitudinal structural magnetic resonance imaging was acquired at baseline, following binge EtOH exposure, and after 2 weeks of recovery. Alcohol treatment showed interactions with age and sex in altering whole brain volume: adolescents of both sexes demonstrated inhibited whole brain growth relative to their control counterparts, although significance was only attained in female mice which showed a larger magnitude response to EtOH compared to male mice. In region of interest analyses, the somatosensory cortex and cerebellum showed inhibited growth in male and female adolescent mice exposed to EtOH, but the difference relative to controls did not reach multiple comparison-corrected statistical significance. These data suggest that in mice exposed to binge EtOH treatment, adolescent age of exposure and female sex may confer a higher risk to the detrimental effects of EtOH on brain structure and reinforce the need for direct testing of both sexes.

Poor subjective sleep predicts compromised quality of life but not cognitive impairment in abstinent individuals with Alcohol Use Disorder.

How disrupted sleep contributes to cognitive dysfunction over the dynamic course of Alcohol Use Disorder (AUD) is an emerging topic of investigation. Here, the Pittsburgh Sleep Quality Index (PSQI) was used to evaluate subjective sleep in 90 individuals with AUD sober for an average of 3 months and in 50 healthy controls. Relative to controls, AUD individuals had higher global PSQI scores (worse sleep), higher scores on the Beck Depression Inventory (BDI-II), worse Quality of Life (QoL) indicators, and poorer performance on cognitive composite tests (executive functioning, attention and working memory, visual and verbal learning or memory). Among AUD individuals, a higher PSQI score correlated with a higher BDI-II score and worse QoL, but not with cognitive scales. Also noted in the AUD group were higher global PSQI scores in individuals also diagnosed with major depressive disorder (MDD) or generalized anxiety disorder (GAD). The four variables explained 29.8% of the variance in AUD PSQI scores. In women with AUD, the four factors explained 39.3% of the variance in PSQI scores (MDD was salient); in AUD men, the four measures explained 19.9% of the variance (QoL predominated). Together, these results suggest that poor PSQI-defined sleep does not predict cognitive performance in abstinent AUD individuals and further, that differential factors associate with poor sleep in men and women with AUD.

A prospective study revealing a compounded burden of COVID-19, sex, and clinical diagnosis of alcohol use disorder and HIV infection on quality of life, anxiety, and alcohol use.

The COVID-19 pandemic led to unprecedented restrictions to mitigate disease spread, leading to consequences affecting mental health. Many studies examining COVID-19 pandemic effects on well-being and mental health initiated inquiry after the pandemic onset, whereas we used self-report questionnaires obtained before the pandemic to re-assess the same functions during the pandemic. Participants were drawn from our ongoing longitudinal studies of people with HIV infection, alcohol use disorder (AUD), HIV + AUD comorbidity, and controls. We used phone or mail contact to invite all to participate in our COVID phone survey, which included three self-report questionnaires: Health-related Quality of Life (QoL), State-Trait Anxiety Inventory (STAI), and Alcohol Use Disorder Identification Test (AUDIT). Of 218 eligible participants, 86 responded (July 2020-March 2021): clinical (29 men, 23 women; 17 AUD, 21 HIV, 14 HIV + AUD); control (17 men, 17 women). QoL scores declined, and anxiety symptoms increased from pre-COVID surveys in all groups; clinical women reported greater negative changes than the other groups. QoL subscales revealed COVID-related declines in emotional well-being in all groups, with clinical women reporting additional declines in energy, physical and social functioning, health, and pain increase. Clinical men also reported health declines. Although AUDIT scores were stable in all groups between assessments, changes in AUDIT scores were inversely correlated with QoL scores in clinical women; in clinical men, changes in STAI scores were inversely correlated with QoL scores. Although all groups were adversely affected by the pandemic, the negative effects were greater in the clinical group regardless of diagnosis and greatest in clinical women.

Aging Accelerates Postural Instability in HIV Infection: Contributing Sensory Biomarkers.

People living with HIV infection (PWH) who are adequately treated pharmacologically are now likely to have a near normal life span. Along with this benefit of the aging HIV population are potential physical problems attendant to aging, including postural stability. Whether aging with HIV accelerates age-related liability for postural instability and what sensory factors contribute to imbalance were examined in 227 PWH and 137 people living without HIV (PWoH), age 25 to 75 years. A mixed cross-sectional/longitudinal design revealed steeper aging trajectories of the PWH than PWoH in sway path length, measured as center-of-pressure micro-displacements with a force platform while a person attempted to stand still. Sway paths were disproportionately longer for PWH than PWoH when tested with eyes closed than open. Multiple regression identified objective measures of sensory perception as unique predictors of sway path length, whereas age, sway path length, and self-reports of falls were predictors of standing on one leg, a common measure of ataxia. Knowledge about sensory signs and symptoms of imbalance in postural stability with and without visual information may serve as modifiable risk factors for averting instability and liability for falls in the aging HIV population.

Neuroimaging in alcohol use disorder: From mouse to man.

This article provides an overview of recent advances in understanding the effects of alcohol use disorders (AUD) on the brain from the perspective of magnetic resonance imaging (MRI) research in preclinical models and clinical studies. As a noninvasive investigational tool permitting assessment of morphological, metabolic, and hemodynamic changes over time, MRI offers insight into the dynamic course of alcoholism beginning with initial exposure through periods of binge drinking and escalation, sobriety, and relapse and has been useful in differential diagnosis of neurological diseases associated with AUD. Structural MRI has revealed acute and chronic effects of alcohol on both white and gray matter volumes. MR Spectroscopy, able to quantify brain metabolites in vivo, has shed light on biochemical alterations associated with alcoholism. Diffusion tensor imaging permits microstructural characterization of white matter fiber tracts. Functional MRI has allowed for elucidation of hemodynamic responses at rest and during task engagement. Positron emission tomography, a non-MRI imaging tool, has led to a deeper understanding of alcohol-induced receptor and neurotransmitter changes during various stages of drinking and abstinence. Together, such in vivo imaging tools have expanded our understanding of the dynamic course of alcoholism including evidence for regional specificity of the effects of AUD, hints at mechanisms underlying the shift from casual to compulsive use of alcohol, and profound recovery with sustained abstinence.