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Abstract

Midline orofacial and brain structures, including the multinucleated thalamus, may be differentially sensitive to prenatal alcohol exposure and vulnerable to accelerated aging.Two sets of MRI data separated by 20 years are reported for controls, individuals with fetal alcohol syndrome (FAS), and nondysmorphic individuals with heavy fetal alcohol exposure (FAE). MRI1 included 179 participants with 69 reassessed at MRI2. Segmentation produced estimates of bilateral thalamic volume and 10 bilateral nuclei, which were aggregated into Anterior, Ventral, Posterior, and Medial Volumes. Differences were assessed without and with correction for intracranial volume (ICV).MRI1 revealed stepwise group differences in ICV, total thalamic volume, and Anterior and Ventral regions uncorrected for ICV, where Controls>FAE>FAS. Corrected for ICV, the smaller volumes endured in the Anterior and Ventral regions, although differences between FAE and FAS groups were attenuated. Nuclei volumes were selectively smaller in the alcohol-exposed groups than controls even after controlling for ICV. Longitudinally, thalamic volumes typically declined over time maintaining the stepwise effects and with little evidence for accelerated decline in the FAE or FAS groups.These novel data revealed stable deficits in thalamic nuclei of the groups with heavy fetal alcohol exposure. After 20 years, the deficits endured but without accelerated age-related decline and following the same aging pattern as controls. Despite parallel aging functions in all groups, ICV adjustment yielded volume deficits localized to the anterior and ventral thalamic nuclei, differing from patterns in the remaining thalamic nuclei and cortical brain structures.

View details for DOI 10.1016/j.bpsc.2025.04.002

View details for PubMedID 40254272

Abstract

OBJECTIVE: Pharmacologically-treated people living with HIV infection have near-normal life spans with more than 50% living into at-risk age for dementia and a disproportionate number relative to uninfected people engaging in unhealthy drinking. Accelerated aging in HIV occurs in some brain structures including the multinucleated thalamus. Unknown is whether aging with HIV affects thalamic nuclei and associated functions differentially and whether the common comorbidity of alcohol use disorder (AUD)+HIV accelerates aging.METHODS: This mixed cross-sectional/longitudinal design examined 216 control, 69 HIV, and 74 HIV+AUD participants, age 25-75years old at initial visit, examined 1-8 times. MRI thalamic volumetry, parcellated using THalamus Optimized Multi-Atlas Segmentation (THOMAS), identified 10 nuclei grouped into 4 functional regions for correlation with age and measures of neuropsychological, clinical, and hematological status.RESULTS: Aging in the control group was best modeled with quadratic functions in the Anterior and Ventral regions and with linear functions in the Medial and Posterior regions. Relative to controls, age-related decline was even steeper in the Anterior and Ventral regions of the HIV group and in the Anterior region of the comorbid group. Anterior volumes of each HIV group declined significantly faster after age 50 (HIV=-2.4%/year; HIV+AUD=-2.8%/year) than that of controls (-1.8%/year). Anterior and Ventral volumes were significantly smaller in the HIV+AUD than HIV-only group when controlling for infection factors. Although compared with controls HIV+AUD declined faster than HIV alone, the two HIV groups did not differ significantly from each other in aging rates. Declining Attention/Working Memory and Motor Skills performance correlated with Anterior and Posterior volume declines in the HIV+AUD group.CONCLUSIONS: Regional thalamic volumetry detected normal aging declines, differential and accelerated volume losses in HIV, relations between age-related nuclear and performance declines, and exacerbation of volume declines in comorbid AUD contributing to functional deficits.

View details for DOI 10.1016/j.nicl.2024.103684

View details for PubMedID 39423567

Abstract

The thalamus, with its reciprocal connections to and from cortical, subcortical, and cerebellar regions, is a central active participant in multiple functional brain networks. Structural MRI studies measuring the entire thalamus without respect to its regional or nuclear divisions report volume shrinkage in diseases including HIV infection, alcohol use disorder (AUD), and their comorbidity (HIV+AUD). Here, we examined relations between thalamic subregions (anterior, ventral, medial, and posterior) and neuropsychological functions (attention/working memory, executive functioning, episodic memory, and motor skills). Volumes of thalamic subregions were derived from automatic segmentations of standard T1 weighted MRIs of 65 individuals with HIV, 189 with AUD, 80 with HIV+AUD comorbidity, and 141 healthy controls (CTRL). Total thalamic volume was smaller and cognitive and motor composite scores were lower in the three diagnostic groups relative to the CTRL group. The AUD and HIV+AUD groups had significantly smaller thalamic subregional volumes than the CTRL group. The HIV+AUD group had smaller anterior thalamic volume than the HIV-only group and smaller ventral thalamic volume than the AUD-only group. In the HIV+AUD group, memory scores correlated with anterior thalamic volumes, attention/working memory scores correlated with posterior and medial thalamic volumes, and motor skill scores correlated with posterior thalamic volumes. Exploratory analyses focused on the HIV+AUD group indicated that within the posterior thalamic region, the pulvinar and medial geniculate nuclei were related to attention/working memory scores, and the pulvinar was related to motor skills scores. This study is novel in locating volume deficits in specific thalamic subregions, in addition to the thalamus as a whole, in HIV, AUD, and their comorbidity and in identifying functional ramifications of these deficits. Taken together, this study highlights the relevance of thalamic subregional volume deficits to dissociable cognitive and motor processes.

View details for DOI 10.1016/j.brainresbull.2024.111085

View details for PubMedID 39343322

View details for DOI 10.1038/s42256-024-00882-y

View details for Web of Science ID 001287474600001

Abstract

Postural instability and brain white matter hyperintensities (WMH) are both noted markers of normal aging and alcohol use disorder (AUD). Here, we questioned what variables contribute to sway path/WMH relations in individuals with AUD and healthy control participants.The data comprised 404 balance platform sessions, yielding sway path length and MRI acquired cross-sectionally or longitudinally, in 102 control and 158 AUD participants, ages 25-80 years. Balance sessions were typically conducted on the same day as MRI FLAIR acquisitions, permitting WMH volume quantification. Factors considered in multiple regression analyses as potential contributors to relations 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.Initial analysis identified diagnosis, age, sex, and race as significant contributors to observed sway path/WMH relations. Inclusion of these factors as predictors in multiple regression analysis substantially attenuated the sway/WMH relations 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, possibly a reflection of the younger age of the Black sample.Longer sway paths were related to larger WMH volumes in healthy men and women, with and without AUD. Critically, however, age nearly fully accounted for these relations.

View details for DOI 10.1016/j.bpsc.2024.03.005

View details for PubMedID 38569932

Abstract

With aging, people living with HIV (PLWH) 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 PLWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables.Mixed cross-sectional/longitudinal data acquired over 15 years in 141 PLWH and 102 age-range matched controls, 25-80 years old.Multimodal structural MRI data were quantified for 7 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 non-path data on sway path-WMH relations.In simple correlations, longer sway paths were associated with larger WMH volumes in PWLH 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 2-point pedal discrimination. Although the sway-WMH relations in PLWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for 5 of the 7 regions in the eyes-open condition.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.

View details for DOI 10.1097/QAD.0000000000003894

View details for PubMedID 38537080

Abstract

Background: Childhood abuse is an underappreciated source of stress, associated with adverse mental and physical health consequences. Childhood abuse has been directly associated with risky behavior thereby increasing the likelihood of alcohol misuse and risk of HIV infection, conditions associated with brain structural and functional deficits. Here, we examined the neural and behavioral correlates of childhood trauma history in alcohol use disorder (AUD), HIV infection (HIV), and their comorbidity (AUD+HIV).Methods: Occurrence of childhood trauma was evaluated by retrospective interview. Cortical (frontal, temporal, parietal, and occipital), subcortical (hippocampus, amygdala), and regional frontal volumes were derived from structural MRI, adjusted for intracranial volume and age. Test scores of executive functioning, attention/working memory, verbal/visual learning, verbal/visual memory, and motor speed functional domains were standardized on age and education of a laboratory control group.Results: History of childhood abuse was associated with smaller frontal lobe volumes regardless of diagnosis. For frontal subregional volumes, history of childhood abuse was selectively associated with smaller orbitofrontal and supplementary motor volumes. In participants with a child abuse history, poorer verbal/visual memory performance was associated with smaller orbitofrontal and frontal middle volumes, whereas in those without childhood abuse, poorer verbal/visual memory performance was associated with smaller orbitofrontal, frontal superior, and supplemental motor volumes.Conclusions: Taken together, these results comport with and extend the findings that childhood abuse is associated with brain and behavioral sequelae in AUD, HIV, and AUD+HIV comorbidity. Further, these findings suggest that sequelae of abuse in childhood may be best conceptualized as a spectrum disorder as significant deficits may be present in those who may not meet criteria for a formal trauma-related diagnosis yet may be suffering enduring stress effects on brain structural and functional health.

View details for DOI 10.1016/j.ynstr.2024.100608

View details for PubMedID 38323165

Abstract

Anomalous brain development and mental health problems are prevalent in fetal alcohol spectrum disorders (FASD), but there is a paucity of longitudinal brain imaging research into adulthood. This study presents long-term follow-up of brain volumetrics in a cohort of participants with FASD.To test whether brain tissue declines faster with aging in individuals with FASD compared with control participants.This cohort study used magnetic resonance imaging (MRI) data collected from individuals with FASD and control individuals (age 13-37 years at first magnetic resonance imaging [MRI1] acquired 1997-2000) compared with data collected 20 years later (MRI2; 2018-2021). Participants were recruited for MRI1 through the University of Washington Fetal Alcohol Syndrome (FAS) Follow-Up Study. For MRI2, former participants were recruited by the University of Washington Fetal Alcohol and Drug Unit. Data were analyzed from October 2022 to August 2023.Intracranial volume (ICV) and regional cortical and cerebellar gray matter, white matter, and cerebrospinal fluid volumes were quantified automatically and analyzed, with group and sex as between-participant factors and age as a within-participant variable.Of 174 individuals with MRI1 data, 48 refused participation, 36 were unavailable, and 24 could not be located. The remaining 66 individuals (37.9%) were rescanned for MRI2, including 26 controls, 18 individuals with nondysmorphic heavily exposed fetal alcohol effects (FAE; diagnosed prior to MRI1), and 22 individuals with FAS. Mean (SD) age was 22.9 (5.6) years at MRI1 and 44.7 (6.5) years at MRI2, and 35 participants (53%) were male. The FAE and FAS groups exhibited enduring stepped volume deficits at MRI1 and MRI2; volumes among control participants were greater than among participants with FAE, which were greater than volumes among participants with FAS (eg, mean [SD] ICV: control, 1462.3 [119.3] cc at MRI1 and 1465.4 [129.4] cc at MRI2; FAE, 1375.6 [134.1] cc at MRI1 and 1371.7 [120.3] cc at MRI2; FAS, 1297.3 [163.0] cc at MRI1 and 1292.7 [172.1] cc at MRI2), without diagnosis-by-age interactions. Despite these persistent volume deficits, the FAE participants and FAS participants showed patterns of neurodevelopment within reference ranges: increase in white matter and decrease in gray matter of the cortex and decrease in white matter and increase in gray matter of the cerebellum.The findings of this cohort study support a nonaccelerating enduring, brain structural dysmorphic spectrum following prenatal alcohol exposure and a diagnostic distinction based on the degree of dysmorphia. FASD was not a progressive brain structural disorder by middle age, but whether accelerated decline occurs in later years remains to be determined.

View details for DOI 10.1001/jamanetworkopen.2023.43618

View details for PubMedID 37976065

Abstract

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.

View details for DOI 10.1016/j.ynirp.2023.100179

View details for PubMedID 37916059

Abstract

Antiretroviral treatment has enabled people living with HIV infection to have a near-normal lifespan. With longevity come 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.Longitudinal MRI-FLAIR data were acquired over 15 years in 179 controls, 204 AUD participants, 70 with HIV, and 75 comorbid for HIV+AUD. White matter hyperintensity (WMH) volumes were quantified and localized and their functional relevance was examined with cognitive and motor testing.The three diagnostic groups each had larger WMH volumes than controls. Although all four groups exhibited accelerating volume increases with aging, only the HIV groups showed faster WMH enlargement than controls; 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 three diagnostic groups.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.

View details for DOI 10.1016/j.biopsych.2023.07.023

View details for PubMedID 37597798

Abstract

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.

View details for DOI 10.1016/j.jpsychires.2023.05.033

View details for PubMedID 37230007

Abstract

Before the introduction of antiretroviral therapy, human immunodeficiency virus (HIV) infection was often accompanied by central nervous system (CNS) opportunistic infections and HIV encephalopathy marked by profound structural and functional alterations detectable with neuroimaging. Treatment with antiretroviral therapy nearly eliminated CNS opportunistic infections, while neuropsychiatric impairment and peripheral nerve and organ damage have persisted among virally suppressed people with HIV (PWH), suggesting ongoing brain injury. Neuroimaging research must use methods sensitive for detecting subtle HIV-associated brain structural and functional abnormalities, while allowing for adjustments for potential confounders, such as age, sex, substance use, hepatitis C coinfection, cardiovascular risk, and others. Here, we review existing and emerging neuroimaging tools that demonstrated promise in detecting markers of HIV-associated brain pathology and explore strategies to study the impact of potential confounding factors on these brain measures. We emphasize neuroimaging approaches that may be used in parallel to gather complementary information, allowing efficient detection and interpretation of altered brain structure and function associated with suboptimal clinical outcomes among virally suppressed PWH. We examine the advantages of each imaging modality and systematic approaches in study design and analysis. We also consider advantages of combining experimental and statistical control techniques to improve sensitivity and specificity of biotype identification and explore the costs and benefits of aggregating data from multiple studies to achieve larger sample sizes, enabling use of emerging methods for combining and analyzing large, multifaceted data sets. Many of the topics addressed in this article were discussed at the National Institute of Mental Health meeting "Biotypes of CNS Complications in People Living with HIV," held in October 2021, and are part of ongoing research initiatives to define the role of neuroimaging in emerging alternative approaches to identifying biotypes of CNS complications in PWH. An outcome of these considerations may be the development of a common neuroimaging protocol available for researchers to use in future studies examining neurological changes in the brains of PWH.

View details for DOI 10.1093/infdis/jiac387

View details for PubMedID 36930637

Abstract

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).Volumetric MRI (CNS) and two-point pedal discrimination (PNS) were tested as substrates of stance instability measured with balance platform posturography.125 PWH and 88 PWoH underwent balance testing and brain MRI.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.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.

View details for DOI 10.1097/QAD.0000000000003531

View details for PubMedID 36927610

Abstract

Excessive alcohol use curtails longevity by rendering intoxicated individuals vulnerable to heightened risk from accidents, violence, and alcohol poisoning and chronically heavy drinkers vulnerable to accelerating age-related medical and psychiatric conditions that can be life-threatening (Yoon et al., 2020). Thus, studies of factors influencing age-alcohol interactions must consider the potential that the alcohol use disorder (AUD) population may not represent the oldest ages of the unaffected population and may well have accrued comorbidities associated with both AUD and aging itself. Herein, we focus on the aging of the brains of men and women with AUD, keeping AUD contextual factors in mind. Knowledge of the potential influence of the AUD-associated co-factors on the condition of brain structure may lead to identifying modifiable risk factors to avert physical declines and may reverse or arrest further AUD-related degradation of the brain. In this narrative review, we 1) describe quantitative, controlled studies of brain macrostructure and microstructure of adults with AUD, 2) consider the possibility of recovery of brain integrity through harm reduction with sustained abstinence or reduced drinking, and 3) speculate on the ramifications of accelerated aging in AUD as contributing to age-related dementia.

View details for DOI 10.1016/j.alcohol.2022.06.002

View details for PubMedID 35781021

Abstract

BACKGROUND: Accurate measurement of trajectories in longitudinal studies, considered the gold standard method for tracking functional growth during adolescence, decline in aging, and change after head injury, is subject to confounding by testing experience.METHODS: We measured change in cognitive and motor abilities over four test sessions (baseline and three annual assessments) in 154 male and 165 female participants (baseline age 12-21years) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. At each of the four test sessions, these participants were given a test battery using computerized administration and traditional pencil and paper tests that yielded accuracy and speed measures for multiple component cognitive (Abstraction, Attention, Emotion, Episodic memory, Working memory, and General Ability) and motor (Ataxia and Speed) functions. The analysis aim was to dissociate neurodevelopment from testing experience by using an adaptation of the twice-minus-once tested method, which calculated the difference between longitudinal change (comprising developmental plus practice effects) and practice-free initial cross-sectional performance for each consecutive pairs of test sessions. Accordingly, the first set of analyses quantified the effects of learning (i.e., prior test experience) on accuracy and after speed domain scores. Then developmental effects were determined for each domain for accuracy and speed having removed the measured learning effects.RESULTS: The greatest gains in performance occurred between the first and second sessions, especially in younger participants, regardless of sex, but practice gains continued to accrue thereafter for several functions. For all 8 accuracy composite scores, the developmental effect after accounting for learning was significant across age and was adequately described by linear fits. The learning-adjusted developmental effects for speed were adequately described by linear fits for Abstraction, Emotion, Episodic Memory, General Ability, and Motor scores, although a nonlinear fit was better for Attention, Working Memory, and Average Speed scores.CONCLUSION: Thus, what appeared as accelerated cognitive and motor development was, in most cases, attributable to learning. Recognition of the substantial influence of prior testing experience is critical for accurate characterization of normal development and for developing norms for clinical neuropsychological investigations of conditions affecting the brain.

View details for DOI 10.1186/s12874-022-01606-9

View details for PubMedID 35751025

Abstract

A neural substrate of alcohol-related instability of gait and balance is the cerebellum. Whether disruption of neural communication between cerebellar and cortical brain regions exerts an influence on ataxia in alcohol use disorder (AUD) was the focus of this study.Study groups comprised 32 abstinent AUD participants and 22 age- and sex-matched healthy controls (CTL). All participants underwent clinical screening, motor testing, and resting-state functional MR imaging analyzed for functional connectivity (FC) among 90 regions across the whole cerebrum and cerebellum. Ataxia testing quantified gait and balance with the Fregly-Graybiel Ataxia Battery conducted with and without vision.The AUD group achieved lower scores than the CTL group on balance performance, which was disproportionately worse for eyes open than eyes closed in the AUD relative to the CTL group. Differences in ataxia were accompanied by differences in FC marked by cerebellar-frontal and cerebellar-parietal hyperconnectivity and cortico-cortical hypoconnectivity in the AUD relative to the control group. Lifetime alcohol consumption correlated significantly with AUD-related FC aberrations, which explained upwards of 69% of the AUD ataxia score variance.Heavy, chronic alcohol consumption is associated with disorganized neural communication among cerebellar-cortical regions and contributes to ataxia in AUD. Ataxia, which is known to accelerate with age and be exacerbated with AUD, can threaten functional independence. Longitudinal studies are warranted to address whether extended sobriety quells ataxia and normalizes aberrant FC contributing to instability.

View details for DOI 10.1016/j.drugalcdep.2022.109435

View details for PubMedID 35395501

Abstract

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.

View details for DOI 10.1007/s11481-021-10039-y

View details for PubMedID 34997916

Abstract

BACKGROUND: Episodic memory deficits occur in alcohol use disorder (AUD), but their anatomical substrates remain in question. Although persistent memory impairment is classically associated with limbic circuitry disruption, learning and retrieval of new information also relies on frontal systems. Despite AUD vulnerability of frontal lobe integrity, relations between frontal regions and memory processes have been under-appreciated.METHODS: Participants included 91 AUD (49 with a drug diagnosis history) and 36 controls. Verbal and visual episodic memory scores were age- and education-corrected. Structural magnetic resonance imaging (MRI) data yielded regional frontal lobe (precentral, superior, orbital, middle, inferior, supplemental motor, and medial) and total hippocampal volumes.RESULTS: AUD were impaired on all memory scores and had smaller precentral frontal and hippocampal volumes than controls. Orbital, superior, and inferior frontal volumes and lifetime alcohol consumption were independent predictors of episodic memory in AUD. Selectivity was established with a double dissociation, where orbital frontal volume predicted verbal but not visual memory, whereas inferior frontal volumes predicted visual but not verbal memory. Further, superior frontal volumes predicted verbal memory in AUD alone, whereas orbital frontal volumes predicted verbal memory in AUD+drug abuse history.CONCLUSIONS: Selective relations among frontal subregions and episodic memory processes highlight the relevance of extra-limbic regions in mnemonic processes in AUD. Memory deficits resulting from frontal dysfunction, unlike the episodic memory impairment associated with limbic dysfunction, may be more amenable to recovery with cessation or reduction of alcohol misuse and may partially explain the heterogeneity in episodic memory abilities in AUD.

View details for DOI 10.1016/j.drugalcdep.2021.109058

View details for PubMedID 34610518

Abstract

Alcohol use disorder (AUD) is widely associated with cerebellar dysfunction and altered cerebro-cerebellar functional connectivity (FC) that lead to cognitive impairments. Evidence for this association comes from resting-state functional magnetic resonance imaging (rsfMRI) studies that assess time-averaged measures of FC across the duration of a typical scan. This approach, however, precludes the assessment of potentially FC dynamics happening at faster timescales. In this study, using rsfMRI data, we aim at exploring cerebro-cerebellar FC dynamics in AUD patients (N = 18) and age- and sex-matched controls (N = 18). In particular, we quantified group-level differences in the temporal variability of FC between the posterior cerebellum and large-scale cognitive systems, and we investigated the role of the cerebellum in large-scale brain dynamics in terms of the temporal flexibility and integration of its regions. We found that, relative to controls, the AUD group exhibited significantly greater FC variability between the cerebellum and both the frontoparietal executive control (F1,31 = 7.01, p(FDR) = 0.028) and ventral attention (F1,31 = 7.35, p(FDR) = 0.028) networks. Moreover, the AUD group exhibited significantly less flexibility (F1,31 = 8.61, p(FDR) = 0.028) and greater integration (F1,31 = 9.11, p(FDR) = 0.028) in the cerebellum. Finally, in an exploratory analysis, we found distributed changes in the dynamics of canonical large-scale networks in AUD. Overall, this study brings evidence of AUD-related alterations in dynamic FC within major cerebro-cerebellar networks. This pattern has implications for explaining the development and maintenance of this disorder and improving our understating of the cerebellum's involvement in addiction.

View details for DOI 10.1007/s12311-021-01241-y

View details for PubMedID 33655376

Abstract

The extant literature supports the involvement of the thalamus in the cognitive and motor impairment associated with chronic alcohol consumption, but clear structure/function relationships remain elusive. Alcohol effects on specific nuclei rather than the entire thalamus may provide the basis for differential cognitive and motor decline in Alcohol Use Disorder (AUD). This functional MRI (fMRI) study was conducted in 23 abstinent individuals with AUD and 27 healthy controls to test the hypothesis that functional connectivity between anterior thalamus and hippocampus would be compromised in those with an AUD diagnosis and related to mnemonic deficits. Functional connectivity between 7 thalamic structures [5 thalamic nuclei: anterior ventral (AV), mediodorsal (MD), pulvinar (Pul), ventral lateral posterior (VLP), and ventral posterior lateral (VPL); ventral thalamus; the entire thalamus] and 14 "functional regions" was evaluated. Relative to controls, the AUD group exhibited different VPL-based functional connectivity: an anticorrelation between VPL and a bilateral middle temporal lobe region observed in controls became a positive correlation in the AUD group; an anticorrelation between the VPL and the cerebellum was stronger in the AUD than control group. AUD-associated altered connectivity between anterior thalamus and hippocampus as a substrate of memory compromise was not supported; instead, connectivity differences from controls selective to VPL and cerebellum demonstrated a relationship with impaired balance. These preliminary findings support substructure-level evaluation in future studies focused on discerning the role of the thalamus in AUD-associated cognitive and motor deficits.

View details for DOI 10.1016/j.drugalcdep.2021.108509

View details for PubMedID 33453503

Abstract

Alcohol use disorder (AUD) is recognized as harmful for the developing brain. Numerous studies have sought environmental and genetic risk factors that predict the development of AUD, but recently identified resilience factors have emerged as protective. This chapter reviews normal processes of brain development in adolescence and emerging adulthood, delineates disturbed growth neurotrajectories related to heavy drinking, and identifies potential endogenous, experiential, and time-linked brain markers of resilience. For example, concurrent high dorsolateral prefrontal activation serving inhibitory control and low nucleus accumbens activation serving reward functions engender positive adaptation and low alcohol use. Also discussed is the role that moderating factors have in promoting risk for or resilience to AUD. Longitudinal research on the effects of all levels of alcohol drinking on the developing brain remains crucial and should be pursued in the context of resilience, which is a promising direction for identifying protective biomarkers against developing AUDs.

View details for DOI 10.1016/bs.irn.2021.08.002

View details for PubMedID 34696880

Abstract

Chronic, excessive alcohol consumption is associated with cerebrovascular hypoperfusion, which has the potential to interfere with cognitive processes. Magnetic resonance pulsed continuous arterial spin labeling (PCASL) provides a noninvasive approach for measuring regional cerebral blood flow (CBF) and was used to study 24 men and women with Alcohol Use Disorder (AUD) and 20 age- and sex-matched controls. Two analysis approaches tested group differences: a data-driven, regionally-free method to test for group differences on a voxel-by-voxel basis and a region of interest (ROI) approach, which focused quantification on atlas-determined brain structures. Whole-brain, voxel-wise quantification identified low AUD-related cerebral perfusion in large volumes of medial frontal and cingulate cortices. The ROI analysis also identified lower CBF in the AUD group relative to the control group in medial frontal, anterior/middle cingulate, insular, and hippocampal/amygdala ROIs. Further, years of AUD diagnosis negatively correlated with temporal cortical CBF, and scores on an alcohol withdrawal scale negatively correlated with posterior cingulate and occipital gray matter CBF. Regional volume deficits did not account for AUD CBF deficits. Functional relevance of attenuated regional CBF in the AUD group emerged with positive correlations between episodic working memory test scores and anterior/middle cingulum, insula, and thalamus CBF. The frontolimbic and insular cortical neuroconstellation with dampened perfusion suggests a mechanism of dysfunction associated with these brain regions in AUD.

View details for DOI 10.1016/j.jpsychires.2021.01.053

View details for PubMedID 33592385

Abstract

Importance: Maturation of white matter fiber systems subserves cognitive, behavioral, emotional, and motor development during adolescence. Hazardous drinking during this active neurodevelopmental period may alter the trajectory of white matter microstructural development, potentially increasing risk for developing alcohol-related dysfunction and alcohol use disorder in adulthood.Objective: To identify disrupted adolescent microstructural brain development linked to drinking onset and to assess whether the disruption is more pronounced in younger rather than older adolescents.Design, Setting, and Participants: This case-control study, conducted from January 13, 2013, to January 15, 2019, consisted of an analysis of 451 participants from the National Consortium on Alcohol and Neurodevelopment in Adolescence cohort. Participants were aged 12 to 21 years at baseline and had at least 2 usable magnetic resonance diffusion tensor imaging (DTI) scans and up to 5 examination visits spanning 4 years. Participants with a youth-adjusted Cahalan score of 0 were labeled as no-to-low drinkers; those with a score of greater than 1 for at least 2 consecutive visits were labeled as heavy drinkers. Exploratory analysis was conducted between no-to-low and heavy drinkers. A between-group analysis was conducted between age- and sex-matched youths, and a within-participant analysis was performed before and after drinking.Exposures: Self-reported alcohol consumption in the past year summarized by categorical drinking levels.Main Outcomes and Measures: Diffusion tensor imaging measurement of fractional anisotropy (FA) in the whole brain and fiber systems quantifying the developmental change of each participant as a slope.Results: Analysis of whole-brain FA of 451 adolescents included 291 (64.5%) no-to-low drinkers and 160 (35.5%) heavy drinkers who indicated the potential for a deleterious association of alcohol with microstructural development. Among the no-to-low drinkers, 142 (48.4%) were boys with mean (SD) age of 16.5 (2.2) years and 149 (51.2%) were girls with mean (SD) age of 16.5 (2.1) years and 192 (66.0%) were White participants. Among the heavy drinkers, 86 (53.8%) were boys with mean (SD) age of 20.1 (1.5) years and 74 (46.3%) were girls with mean (SD) age of 20.5 (2.0) years and 142 (88.8%) were White participants. A group analysis revealed FA reduction in heavy-drinking youth compared with age- and sex-matched controls (t154=-2.7, P=.008). The slope of this reduction correlated with log of days of drinking since the baseline visit (r156=-0.21, 2-tailed P=.008). A within-participant analysis contrasting developmental trajectories of youths before and after they initiated heavy drinking supported the prediction that drinking onset was associated with and potentially preceded disrupted white matter integrity. Age-alcohol interactions (t152=3.0, P=.004) observed for the FA slopes indicated that the alcohol-associated disruption was greater in younger than older adolescents and was most pronounced in the genu and body of the corpus callosum, regions known to continue developing throughout adolescence.Conclusions and Relevance: This case-control study of adolescents found a deleterious association of alcohol use with white matter microstructural integrity. These findings support the concept of heightened vulnerability to environmental agents, including alcohol, associated with attenuated development of major white matter tracts in early adolescence.

View details for DOI 10.1001/jamapsychiatry.2020.4064

View details for PubMedID 33377940

View details for DOI 10.1176/appi.ajp.2020.20091323

View details for PubMedID 33135471

Abstract

Traditionally, the desired successful recovery from alcohol dependence has required complete abstinence, without transgression, for a sustained period, ideally the rest of one's life. This stringent definition marks a goal that is unachievable by a majority of men and women with Alcohol Use Disorder (AUD) despite sincere efforts to stop drinking. While perhaps ideal, that goal of complete and permanent abstinence puts behavioral and pharmacological treatment at substantial risk for failure. Here we ask, are there acceptable alternatives to abstinence, and how are they established and substantiated?

View details for DOI 10.1111/acer.14409

View details for PubMedID 32623744

View details for DOI 10.1111/adb.12746

View details for Web of Science ID 000528674100024

Abstract

The extensive prenatal developmental growth period of the cerebellum renders it vulnerable to unhealthy environmental agents, especially alcohol. Fetal alcohol spectrum disorders (FASD) is marked by neurodysmorphology including cerebral and cerebellar volume deficits, but the cerebellar lobular deficit profile has not been delineated. Legacy MRI data of 114 affected and 60 unaffected adolescents and young adults were analyzed for lobular gray matter volume and revealed graded deficits supporting a spectrum of severity. Graded deficits were salient in intracranial volume (ICV), where the fetal alcohol syndrome (FAS) group was smaller than the fetal alcohol effects (FAE) group, which was smaller than the controls. Adjusting for ICV, volume deficits were present in VIIB and VIIIA of the FAE group and were more widespread in FAS and included lobules I, II, IV, V, VI, Crus II, VIIB, and VIIA. Graded deficits (FAS

View details for DOI 10.1093/cercor/bhaa020

View details for PubMedID 32133485

Abstract

Alcohol use and misuse is increasing among women. Although the prevalence of drinking remains higher in men than women, the gender gap is narrowing. This narrative review focuses on the cognitive sequelae of alcohol consumption in women. Studies of acute alcohol effects on cognition indicate that women typically perform worse than men on tasks requiring divided attention, memory, and decision-making. Beneficial effects of moderate alcohol consumption on cognition have been reported; however, a number of studies have cautioned that other factors may be driving that association. Although chronic heavy drinking affects working memory, visuospatial abilities, balance, emotional processing, and social cognition in women and men, sex differences mark the severity and specific profile of functional deficits. The accelerated or compressed progression of alcohol-related problems and their consequences observed in women relative to men, referred to as "telescoping," highlights sex differences in the pharmacokinetics, pharmacodynamics, cognitive, and psychological consequences of alcohol. Brain volume deficits affecting multiple systems, including frontolimbic and frontocerebellar networks, contribute to impairment. Taken together, sex-related differences highlight the complexity of this chronic disease in women and underscore the relevance of examining the roles of age, drinking patterns, duration of abstinence, medical history, and psychiatric comorbidities in defining and understanding alcohol-related cognitive impairment.

View details for DOI 10.35946/arcr.v40.2.03

View details for PubMedID 32923307

Abstract

Postural stability is a multi-factorial skill maintained implicitly. Components of quiet standing can decline with Alcohol Use Disorder (AUD), cause instability, and disrupt activities of daily living (ADL). To examine how stability factors contribute to ADL and balance, 638 force platform testing sessions measured sway paths acquired during quiet standing in 151 AUD and 96 control men and women, age 25-75. Structural equation (seq) path analysis estimated contributions from age, diagnosis, and sensory perception to sway and measures of ADL and roadside ataxia testing. Whether eyes were open or closed, older AUD and control participants had longer sway paths than younger ones; older men had longer sway paths than older women. Although each sensory ability tested declined with aging, different factor constellations influenced ADL, ataxia scores, or sway path. Seq-path analysis indicated that ADL was strongly dependent on sensory (but not cognitive) systems with sway-path length accounting for upwards of 25% of variance. Within the AUD group, an index of historically-experienced withdrawal symptoms was a common predictor of stability regardless of vision condition. The greatest variance measured by the seq-path model was for predicting platform sway and simple ataxia testing of one-leg standing even though these measures were affected by different predictor variables: strong predictors of one-leg standing were diagnosis and age (R2 = 39.6%-43.2%), whereas strong predictors of sway-path length were sensory factors and withdrawal index (R2 = 22.0%-22.9%). These findings present evidence for appreciating selective factors that contribute to declining postural stability and to liability for compromised quality of life in AUD.

View details for DOI 10.1111/adb.12966

View details for PubMedID 33098738

Abstract

BACKGROUND: The cerebellum is a target of alcoholism-related brain damage in adults, yet no study has prospectively tracked deviations from normal cerebellar growth trajectories in adolescents before and after initiating drinking.METHODS: Magnetic resonance imaging tracked developmental volume trajectories of 10 cerebellar lobule and vermis tissue constituents in 548 no/low drinking youths age 12 to 21 years at induction into this 5-site, NCANDA (National Consortium on Alcohol and NeuroDevelopment in Adolescence) study. Over the 3- to 4-year longitudinal examination yielding 2043 magnetic resonance imaging scans, 328 youths remained no/low drinkers, whereas 220 initiated substantial drinking after initial neuroimaging.RESULTS: Normal growth trajectories derived from no/low drinkers indicated that gray matter volumes of lobules V and VI, crus II, lobule VIIB, and lobule X declined faster with age in male youths than in female youths, whereas white matter volumes in crus I and crus II and lobules VIIIA and VIIIB expanded faster in female youths than in male youths; cerebrospinal fluid volume expanded faster in most cerebellar regions of male youths than female youths. Drinkers exhibited accelerated gray matter decline in anterior lobules and vermis, accelerated vermian white matter expansion, and accelerated cerebrospinal fluid volumes expansion of anterior lobules relative to youths who remained no/low drinkers. Analyses including both alcohol and marijuana did not support an independent role for marijuana in alcohol effects on cerebellar gray matter trajectories.CONCLUSIONS: Alcohol use-related cerebellar growth trajectory differences from normal involved anterior lobules and vermis of youths who initiated substantial drinking. These regions are commonly affected in alcohol-dependent adults, raising the possibility that cerebellar structures affected by youthful drinking may be vulnerable to age-alcohol interactions in later adulthood.

View details for DOI 10.1016/j.biopsych.2019.08.026

View details for PubMedID 31653477

Abstract

Alcohol use disorder (AUD) is a complex, dynamic condition that waxes and wanes with unhealthy drinking episodes and varies in drinking patterns and effects on brain structure and function with age. Its excessive use renders chronically heavy drinkers vulnerable to direct alcohol toxicity and a variety of comorbidities attributable to nonalcohol drug misuse, viral infections, and accelerated or premature aging. AUD affects widespread brain systems, commonly, frontolimbic, frontostriatal, and frontocerebellar networks.Multimodal assessment using selective neuropsychological testing and whole-brain neuroimaging provides evidence for AUD-related specific brain structure-function relations established with double dissociations. Longitudinal study using noninvasive imaging provides evidence for brain structural and functional improvement with sustained sobriety and further decline with relapse. Functional imaging suggests the possibility that some alcoholics in recovery can compensate for impairment by invoking brain systems typically not used for a target task but that can enable normal-level performance.Evidence for AUD-aging interactions, indicative of accelerated aging, together with increasing alcohol consumption in middle-age and older adults, put aging drinkers at special risk for developing cognitive decline and possibly dementia. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

View details for DOI 10.1037/neu0000557

View details for Web of Science ID 000482569400002

View details for PubMedID 31448945

Abstract

The World Health Organization estimates a 12-month prevalence rate of 8+% for an alcohol use disorder (AUD) diagnosis in people age 15years and older in the United States and Europe, presenting significant health risks that have the potential of accelerating age-related functional decline. According to neuropathological studies, white matter systems of the cerebellum are vulnerable to chronic alcohol dependence. To pursue the effect of AUD on white matter structure and functions in vivo, this study used T1-weighted, magnetic resonance imaging (MRI) to quantify the total corpus medullare of the cerebellum and a finely grained analysis of its surface in 135 men and women with AUD (mean duration of abstinence, 248d) and 128 age- and sex-matched control participants; subsets of these participants completed motor testing. We identified an AUD-related volume deficit and accelerated aging in the total corpus medullare. Novel deformation-based surface morphometry revealed regional shrinkage of surfaces adjacent to lobules I-V, lobule IX, and vermian lobule X. In addition, accelerated aging was detected in the regional surface areas adjacent to lobules I-V, lobule VI, lobule VIIB, and lobules VIII, IX, and X. Sex differences were not identified for any measure. For both volume-based and surface-based analyses, poorer performance in gait and balance, manual dexterity, and grip strength were linked to greater regional white matter structural deficits. Our results suggest that local deformation of the corpus medullare has the potential of identifying structurally and functionally segregated networks affected in AUD.

View details for PubMedID 30932270

Abstract

Despite the common co-occurrence of cognitive impairment and brain structural deficits in alcoholism, demonstration of relations between regional gray matter volumes and cognitive and motor processes have been relatively elusive. In pursuit of identifying brain structural substrates of impairment in alcoholism, we assessed executive functions (EF), episodic memory (MEM), and static postural balance (BAL) and measured regional brain gray matter volumes of cortical, subcortical, and cerebellar structures commonly affected in individuals with alcohol dependence (ALC) compared with healthy controls (CTRL). ALC scored lower than CTRL on all composite scores (EF, MEM, and BAL) and had smaller frontal, cingulate, insular, parietal, and hippocampal volumes. Within the ALC group, poorer EF scores correlated with smaller frontal and temporal volumes; MEM scores correlated with frontal volume; and BAL scores correlated with frontal, caudate, and pontine volumes. Exploratory analyses investigating relations between subregional frontal volumes and composite scores in ALC yielded different patterns of associations, suggesting that different neural substrates underlie these functional deficits. Of note, orbitofrontal volume was a significant predictor of memory scores, accounting for almost 15% of the variance; however, this relation was evident only in ALC with a history of a non-alcohol substance diagnosis and not in ALC without a non-alcohol substance diagnosis. The brain-behavior relations observed provide evidence that the cognitive and motor deficits in alcoholism are likely a result of different neural systems and support the hypothesis that a number of identifiable neural systems rather than a common or diffuse neural pathway underlies cognitive and motor deficits observed in chronic alcoholism.

View details for DOI 10.1007/s00429-019-01894-w

View details for PubMedID 31161472

Abstract

The comorbidity of Human Immunodeficiency Virus (HIV) infection and alcoholism (ALC) is prevalent. Wernicke's encephalopathy (WE), a neurological disorder resulting from thiamine depletion, has been generally associated with alcoholism but has also been reported in HIV infection. This study examined whether subclinical WE signs could contribute to the heterogeneity of cognitive and motor deficits observed in individuals with both disease conditions (HIV+ALC).61 HIV+ALC individuals and 59 controls were assessed on attention and working memory, production, immediate and delayed episodic memory, visuospatial abilities, and upper limb motor function.Using Caine criteria (dietary deficiency, oculomotor abnormality, cerebellar dysfunction, and altered mental state), HIV+ALC individuals were classified by subclinical WE risk factors.Signs of subclinical WE were present in 20% of the HIV+ALC participants. For attention/working memory, delayed memory, and upper limb motor function, HIV+ALCCaine 2+ (i.e., meeting two or three criteria) demonstrated the most severe deficits, scoring lower than HIV+ALC Caine 1 (i.e., meeting one criterion), HIV+ALC Caine 0 (i.e., meeting no criteria), and controls.The high prevalence of subclinical signs of WE and relevance to performance indicate that this condition should be considered in assessment of HIV-infected individuals, especially when alcoholism comorbidity is known or suspected. Above and beyond clinical factors such as depression, alcoholism and HIV disease-related variables, AIDS, hepatitis C and drug history known to mediate neuropsychological performance, subclinical WE signs could partly explain the heterogeneity in patterns and severity of cognitive and motor impairments in HIV-infected individuals with alcoholism comorbidity.

View details for DOI 10.1097/QAD.0000000000002428

View details for PubMedID 31725430

Abstract

Recent advances in robust and reliable methods of MRI-derived cerebellar lobule parcellation volumetry present the opportunity to assess effects of Alcohol Use Disorder (AUD) on selective cerebellar lobules and relations with indices of nutrition and motor functions. In pursuit of this opportunity, we analyzed high-resolution MRI data acquired in 24 individuals with AUD and 20 age- and sex-matched controls with a 32-channel head coil using three different atlases: the online automated analysis pipeline volBrain Ceres, SUIT, and the Johns Hopkins atlas. Participants had also completed gait and balance examination and hematological analysis of nutritional and liver status, enabling testing of functional meaningfulness of each cerebellar parcellation scheme. Compared with controls, each quantification approach yielded similar patterns of group differences in regional volumes: All three approaches identified AUD-related deficits in total tissue and total gray matter, but only Ceres identified a total white matter volume deficit. Convergent volume differences occurred in lobules I-V, Crus I, VIIIB, and IX. Coefficients of variation (CVs) were <20% for 46 of 56 regions measured and in general were graded: Ceres

View details for DOI 10.1016/j.nicl.2019.101974

View details for PubMedID 31419768

Abstract

BACKGROUND: Life expectancy of successfully treated human immunodeficiency virus (HIV)-infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures.METHODS: This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects. We tested 1) whether localized brain regions in HIV-infected individuals exhibited accelerated aging, or alternatively, nonaccelerated premature aging deficits; and 2) the extent to which alcohol or substance dependence or HCV coinfection altered brain aging trajectories.RESULTS: The HIV-infected cohort exhibited steeper declining volume trajectories than control subjects, consistently in the frontal cortex. Nonaccelerated volume deficits occurred in the temporal, parietal, insular, and cingulate regions of all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV coinfection exacerbated HIV-related volume deficits. Accelerated age interactions in frontal and posterior parietal volumes endured in HIV-infected individuals free of alcohol or substance dependence and HCV infection comorbidities. Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans Aging Cohort Study indices correlated with smaller regional brain volumes in the HIV-infected individuals without alcohol dependence and alcohol-dependent groups.CONCLUSIONS: HIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.

View details for PubMedID 30093343

View details for PubMedID 30047474

Abstract

The prevalence of alcohol misuse increased substantially over a decade in adults, particularly in those aged 65 years or older. Ramifications for brain structural integrity are significant, especially in older adults.To combine cross-sectional, longitudinal data to test age-alcoholism interactions and examine the association between prevalent comorbidities (drug dependence and hepatitis C virus [HCV] infection) and cortical volume deficits in alcohol dependence.During 14 years, 826 structural magnetic resonance images were acquired in 222 individuals with alcohol dependence and 199 age-matched control participants (aged 25-75 years at initial study), parcellated with a common atlas, and adjusted for brain volume. Longitudinal data were available on 116 participants with alcoholism and 96 control participants. DSM-IV criteria determined alcohol and drug diagnoses; serology testing determined HCV status. The study was conducted at SRI International and Stanford University School of Medicine from April 11, 2003, to March 3, 2017.Magnetic resonance imaging-derived regional cortical volumes corrected for supratentorial volume and sex.Of the 222 participants with alcoholism, 156 (70.3%) were men; mean (SD) age was 48.0 (10.0) years; the mean age for the 199 control participants was 47.6 (14.0) years. Participants with alcohol dependence had volume deficits in frontal (t = -5.732, P < .001), temporal (t = -3.151, P = .002), parietal (t = -5.063, P < .001), cingulate (t = -3.170, P = .002), and insular (t = -4.920, P < .001) cortices; deficits were prominent in frontal subregions and were not sex dependent. Accelerated aging occurred in frontal cortex (t = -3.019, P < .02) and precentral (t = -2.691, P < .05) and superior gyri (t = -2.763, P < .05) and could not be attributed to the amount of alcohol consumed, which was greater in younger-onset than older-onset participants with alcoholism (t = 6.1191, P < .001). Given the high drug-dependence incidence (54.5%) in the alcoholism group, analysis examined drug subgroups (cocaine, cannabis, amphetamines, opiates) compared with drug-dependence-free alcoholism and control groups. Although the alcohol plus cocaine (t = -2.310, P = .04) and alcohol plus opiate (t = -2.424, P = .04) groups had smaller frontal volumes than the drug-dependence-free alcoholism group, deficits in precentral (t = -2.575, P = .01), supplementary motor (t = -2.532, P = .01), and medial (t = -2.800, P = .01) volumes endured in drug-dependence-free participants with alcoholism compared with control participants. Those with HCV infection had greater deficits than those without HCV infection in frontal (t = 3.468, P = .01), precentral (t = 2.513, P = .03), superior (t = 2.533, P = .03), and orbital (t = 2.506, P = .03) volumes, yet total frontal (t = 2.660, P = .02), insular (t = 3.526, P = .003), parietal (t = 2.414, P = .03), temporal (t = 3.221, P = .005), and precentral (t = 3.180, P = .01) volume deficits persisted in the uninfected participants with alcoholism compared with control participants with known HCV status.Drug dependence and HCV infection compounded deleterious effects of alcohol dependence on frontal cortical volumes but could not account for the frontally distributed volume deficits in the drug-free participants with alcoholism. We speculate that age-alcohol interactions notable in frontal cortex put older adults at heightened risk for age-associated neurocompromise even if alcohol misuse is initiated later in life.

View details for PubMedID 29541774

View details for PubMedCentralID PMC5875381

Abstract

OBJECTIVE: The authors sought evidence for altered adolescent brain growth trajectory associated with moderate and heavy alcohol use in a large national, multisite, prospective study of adolescents before and after initiation of appreciable alcohol use.METHOD: This study examined 483 adolescents (ages 12-21) before initiation of drinking and 1 and 2 years later. At the 2-year assessment, 356 participants continued to meet the study's no/low alcohol consumption entry criteria, 65 had initiated moderate drinking, and 62 had initiated heavy drinking. MRI was used to quantify regional cortical and white matter volumes. Percent change per year (slopes) in adolescents who continued to meet no/low criteria served as developmental control trajectories against which to compare those who initiated moderate or heavy drinking.RESULTS: In no/low drinkers, gray matter volume declined throughout adolescence and slowed in many regions in later adolescence. Complementing gray matter declines, white matter regions grew at faster rates at younger ages and slowed toward young adulthood. Youths who initiated heavy drinking exhibited an accelerated frontal cortical gray matter trajectory, divergent from the norm. Although significant effects on trajectories were not observed in moderate drinkers, their intermediate position between no/low and heavy drinkers suggests a dose effect. Neither marijuana co-use nor baseline volumes contributed significantly to the alcohol effect.CONCLUSIONS: Initiation of drinking during adolescence, with or without marijuana co-use, disordered normal brain growth trajectories. Factors possibly contributing to abnormal cortical volume trajectories include peak consumption in the past year and family history of alcoholism.

View details for PubMedID 29084454