Obesity/overweight is reported to affect MR-measured brain tissue volume and white matter (WM) signal intensity. This study investigated possible effects of fat on these measures, using pig fat on three participants at a 4T magnet. Grey matter volumes in the presence of fat were lower than baseline measures. Total WM volumes in the presence of fat were higher than baseline measures. WM hypo-intensities on T1-weighted images were higher in the presence of fat than baseline measures. Therefore physical effects of head fat of obese/overweight individual may at least, partly contribute to the association of obesity/overweight with MR structural measures.

Recent MRS studies have indicated that a higher body mass index (BMI) is associated with lower brain metabolite levels. Generally, individuals with higher BMIs have more body fat deposits than individuals with normal BMIs. This single-voxel spectroscopy (SVS) study investigated possible effects of fat on MR-measured metabolite signal areas, which may at least partly explain the observed associations of BMI with MR-measured brain metabolite levels in vivo. SVS data were acquired at 4 T from a phantom containing N-acetylaspartate, glutamate and creatine, as well as from three healthy male adults. Back fat obtained from pig was used to assess the effects of fat on metabolite signals. With the same voxel size and placement, the phantom was first scanned without fat (baseline), and then with 0.7-cm- and 1.4-cm-thick fat layers placed on it. Each participant was also scanned first without fat and then with two 0.7-cm fat layers, one placed beneath the occiput and the other on the forehead. Two spectra were acquired per participant from the anterior cingulate and the parieto-occipital cortices. The metabolite resonance and corresponding water peak areas were then fitted and metabolite to water signal ratios were used for analyses. In both phantom and in vivo experiments, the metabolite-to-water ratios decreased in the presence of fat relative to baseline metabolite-to-water ratios. The reduced metabolite signals in the presence of fat reported here are reminiscent of the negative correlations observed between BMI and MR-measured metabolite levels. These apparent physical effects of fat have potentially far-reaching consequences for the accuracy of MR measurements of brain metabolite levels and their interpretation, particularly when large fat stores exist around the skull, such as in individuals with higher BMI.

Posttraumatic stress disorder (PTSD) patients have low cortical concentrations of γ-aminobutyric acid (GABA) and elevated glutamate (Glu) as measured by proton magnetic resonance spectroscopy ((1)H MRS). Alcohol use disorder (AUD) is highly comorbid with PTSD, but the neurobiological underpinnings are largely unknown. We wanted to determine if PTSD patients with AUD have normalized cortical GABA and Glu levels in addition to metabolite alterations common to AUD. We compared brain metabolite concentrations in 10 PTSD patients with comorbid AUD (PAUD) with concentrtations in 28 PTSD patients without AUD and in 20 trauma-exposed controls (CON) without PTSD symptoms. We measured concentrations of GABA, Glu, N-acetylaspartate (NAA), creatine- (Cr) and choline-containing metabolites (Cho), and myo-Inositol (mI) in three cortical brain regions using (1)H MRS and correlated them with measures of neurocognition, insomnia, PTSD symptoms, and drinking severity. In contrast to PTSD, PAUD exhibited normal GABA and Glu concentrations in the parieto-occipital and temporal cortices, respectively, but lower Glu and trends toward higher GABA levels in the anterior cingulate cortex (ACC). Temporal NAA and Cho as well as mI in the ACC were lower in PAUD than in both PTSD and CON. Within PAUD, more cortical GABA and Glu correlated with better neurocognition. Heavy drinking in PTSD is associated with partially neutralized neurotransmitter imbalance, but also with neuronal injury commonly observed in AUD.

Background

Although comorbid substance misuse is common in alcohol dependence, and polysubstance abusers (PSU) represent the largest group of individuals seeking treatment for drug abuse today, we know little about potential brain abnormalities in this population. Brain magnetic resonance spectroscopy studies of mono-substance use disorders (e.g., alcohol or cocaine) reveal abnormal levels of cortical metabolites (reflecting neuronal integrity, cell membrane turnover/synthesis, cellular bioenergetics, gliosis) and altered concentrations of glutamate and γ-aminobutyric acid (GABA). The concurrent misuse of several substances may have unique and different effects on brain biology and function compared to any mono-substance misuse.

Methods

High field brain magnetic resonance spectroscopy at 4 T and neurocognitive testing were performed at one month of abstinence in 40 alcohol dependent individuals (ALC), 28 alcohol dependent PSU and 16 drug-free controls. Absolute metabolite concentrations were calculated in anterior cingulate (ACC), parieto-occipital (POC) and dorso-lateral prefrontal cortices (DLPFC).

Results

Compared to ALC, PSU demonstrated significant metabolic abnormalities in the DLPFC and strong trends to lower GABA in the ACC. Metabolite levels in ALC and light drinking controls were statistically equivalent. Within PSU, lower DLPFC GABA levels are related to greater cocaine consumption. Several cortical metabolite concentrations were associated with cognitive performance.

Conclusions

While metabolite concentrations in ALC at one month of abstinence were largely normal, PSU showed persistent and functionally significant metabolic abnormalities, primarily in the DLPFC. Our results point to specific metabolic deficits as biomarkers in polysubstance misuse and as targets for pharmacological and behavioral PSU-specific treatment.

Background

Increasing age and chronic cigarette smoking are independently associated with adverse effects on multiple aspects of neurocognition in those seeking treatment for alcohol use disorders. However, the potential interactive effects of age and cigarette smoking on neurocognition in early abstinent alcohol-dependent individuals (ALC) have not investigated.

Methods

Cross-sectional performances of never-smoking healthy comparison participants (nvsCOM; n = 39) and 1-month-abstinent, treatment-seeking, never-smoking (nvsALC; n = 30), former-smoking (fsALC; n = 21), and actively smoking (asALC; n = 68) ALC were compared on a comprehensive neurocognitive battery. Domains of functioning evaluated were cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions and working memory. Participants were between 26 and 71 years of age at the time of assessment.

Results

asALC showed steeper age-related effects than nvsCOM on the domains of visuospatial learning, auditory-verbal memory, cognitive efficiency, executive functions, processing speed, and fine motor skills. In pairwise comparisons, fsALC and asALC performed more poorly than both nvsCOM and nvsALC on multiple domains; nvsCOM and nvsALC showed no significant differences. Domain scores for the ALC groups generally fell in the low-to-high-average range of functioning. A clinically significant level of impairment was apparent in only 25% of ALC participants on visuospatial learning, visuospatial memory, and fine motor skills domains. Measures of alcohol use or consumption were not significantly related to neurocognition in the ALC cohorts.

Conclusions

The age-related findings suggest that the combination of active chronic smoking and alcohol dependence in this 1-month-abstinent ALC cohort was associated with greater than normal age-related effects in multiple domains. In general, a low level of clinically significant impairment was observed in the alcohol-dependent participants. The findings from this study, in conjunction with previous research, strongly support smoking cessation interventions for those seeking treatment for alcohol and substance use disorders.

Chronic alcohol-use disorders (AUDs) have been shown to interact with normal age-related volume loss to exacerbate brain atrophy with increasing age. However, chronic cigarette smoking, a highly co-morbid condition in AUD and its influence on age-related brain atrophy have not been evaluated. We performed 1.5 T quantitative magnetic resonance imaging in non-smoking controls [non-smoking light drinking controls (nsCONs); n = 54], smoking light drinking controls (sCONs, n = 34), and one-week abstinent, treatment-seeking alcohol-dependent (ALC) non-smokers (nsALCs, n = 35) and smokers (sALCs, n = 43), to evaluate the independent and interactive effects of alcohol dependence and chronic smoking on regional cortical and subcortical brain volumes, emphasizing the brain reward/executive oversight system (BREOS). The nsCONs and sALCs showed greater age-related volume losses than the nsALCs in the dorsal prefrontal cortex (DPFC), total cortical BREOS, superior parietal lobule and putamen. The nsALCs and sALCs demonstrated smaller volumes than the nsCONs in most cortical region of interests (ROIs). The sCONs had smaller volumes than the nsCONs in the DPFC, insula, inferior parietal lobule, temporal pole/parahippocampal region and all global cortical measures. The nsALCs and sALCs had smaller volumes than the sCONs in the DPFC, superior temporal gyrus, inferior and superior parietal lobules, precuneus and all global cortical measures. Volume differences between the nsALCs and sALCs were observed only in the putamen. Alcohol consumption measures were not related to volumes in any ROI for ALC; smoking severity measures were related to corpus callosum volume in the sCONs and sALCs. The findings indicate that consideration of smoking status is necessary for a better understanding of the factors contributing to regional brain atrophy in AUD.

BACKGROUND: Increasing age and chronic cigarette smoking are independently associated with adverse effects on multiple aspects of neurocognition in those seeking treatment for alcohol use disorders. However, the potential interactive effects of age and cigarette smoking on neurocognition in early abstinent alcohol-dependent individuals (ALC) have not investigated. METHODS: Cross-sectional performances of never-smoking healthy comparison participants (nvsCOM; n = 39) and 1-month-abstinent, treatment-seeking, never-smoking (nvsALC; n = 30), former-smoking (fsALC; n = 21), and actively smoking (asALC; n = 68) ALC were compared on a comprehensive neurocognitive battery. Domains of functioning evaluated were cognitive efficiency, executive functions, fine motor skills, general intelligence, learning and memory, processing speed, visuospatial functions and working memory. Participants were between 26 and 71 years of age at the time of assessment. RESULTS: asALC showed steeper age-related effects than nvsCOM on the domains of visuospatial learning, auditory-verbal memory, cognitive efficiency, executive functions, processing speed, and fine motor skills. In pairwise comparisons, fsALC and asALC performed more poorly than both nvsCOM and nvsALC on multiple domains; nvsCOM and nvsALC showed no significant differences. Domain scores for the ALC groups generally fell in the low-to-high-average range of functioning. A clinically significant level of impairment was apparent in only 25% of ALC participants on visuospatial learning, visuospatial memory, and fine motor skills domains. Measures of alcohol use or consumption were not significantly related to neurocognition in the ALC cohorts. CONCLUSIONS: The age-related findings suggest that the combination of active chronic smoking and alcohol dependence in this 1-month-abstinent ALC cohort was associated with greater than normal age-related effects in multiple domains. In general, a low level of clinically significant impairment was observed in the alcohol-dependent participants. The findings from this study, in conjunction with previous research, strongly support smoking cessation interventions for those seeking treatment for alcohol and substance use disorders.

Background

Alcohol use disorders are related to neurocognitive abnormalities during early abstinence in those seeking treatment for alcohol dependence (ALC). Considerable evidence indicates that chronic cigarette smoking is associated with multiple neurocognitive deficiencies. However, very little is known about the effects of chronic smoking on neurocognitive recovery during early abstinence from alcohol. We evaluated whether cigarette smoking interferes with cognitive improvement during early abstinence from alcohol, a period thought important for maintaining long-term sobriety.

Methods

Neurocognitive functions previously shown to be adversely affected by both alcohol use disorders and chronic cigarette smoking were evaluated. We assessed 35 smoking ALC (sALC) and 34 nonsmoking ALC (nsALC) at approximately 1 and 5 weeks of monitored abstinence.

Results

Although neither group was clinically impaired, both cross-sectional and longitudinal deficiencies were observed in sALC versus nsALC in processing speed, working memory, and auditory-verbal learning and memory. Lifetime alcohol consumption, medical, and psychiatric comorbidities did not predict neurocognitive performance or improvement across assessments. Within sALC, greater drinking and smoking severities were synergistically (more than additively) related to less improvement on visuospatial learning and memory. Former smoking status in the nsALC-mediated group differences in auditory-verbal delayed recall.

Conclusions

Chronic cigarette smoking appears to negatively impact neurocognition during early abstinence from alcohol. Although the cognitive deficiencies observed in this cohort were not in a clinical range of impairment, they should be considered to enhance treatment efficacy. Our findings lend support to integrating smoking cessation as well as the individual assessment of cognition into early ALC treatment. Additionally, there is a need to elucidate the effects of current and former smoking status in future reports of neurocognition.

Background

Over 50% of individuals with alcohol use disorders (AUD) also use other substances; brain structural abnormalities observed in alcohol dependent individuals may not be entirely related to alcohol consumption. This MRI study assessed differences in brain regional tissue volumes between short-term abstinent alcohol dependent individuals without (ALC) and with current substance use dependence (polysubstance users, PSU).

Methods

Nineteen, one-month-abstinent PSU and 40 ALC as well as 27 light-drinkers (LD) were studied on a 1.5 T MR system. Whole brain T1-weighted images were segmented automatically into regional gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) volumes. MANOVA assessed group differences of intracranial volume-normalized tissue volumes of the frontal, parietal, occipital, and temporal lobes and regional subcortical GM volumes. The volumetric measures were correlated with neurocognitive measures to assess their functional relevance.

Results

Despite similar lifetime drinking and smoking histories, PSU had significantly larger normalized WM volumes than ALC in all lobes. PSU also had larger frontal and parietal WM volumes than LD, but smaller temporal GM volumes and smaller lenticular and thalamic nuclei than LD. ALC had smaller frontal, parietal, and temporal GM, thalamic GM and cerebellar volumes than LD. ALC had more sulcal CSF volumes than both PSU and LD.

Conclusion

One-month-abstinent ALC and PSU exhibited different patterns of gross brain structural abnormalities. The larger lobar WM volumes in PSU in the absence of widespread GM volume loss contrast with widespread GM atrophy in ALC. These structural differences may demand different treatment approaches to mitigate specific functionally relevant brain abnormalities.