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Dieter J Meyerhoff

Publications and source records attributed to Dieter J Meyerhoff.

At least 19 recordsLinked to original sources
PubMed2006

Deformation-based morphometry of brain changes in alcohol dependence and abstinence.

Brain atrophy associated with chronic alcohol consumption is partially reversible after cessation of drinking. Recovering alcoholics (RA, 45+/-8 years) were studied with MRI within 1 week of entering treatment, with follow-up at 8 months. Light drinkers (LD) were studied with MRI twice 1 year apart. For each participant, deformation maps of baseline structure and longitudinal size changes between baseline and follow-up scans were created using nonlinear registration techniques. ANCOVA assessed group differences and regression methods examined relationships between deformation maps and measures of drinking severity or baseline atrophy. At baseline, RA showed significant atrophy in the frontal and temporal lobes. Longitudinally, abstainers recovered tissue volumes significantly faster than LD in parietal and frontal lobes. When comparing abstainers to relapsers, additional regions with significantly greater recovery in abstainers were temporal lobes, thalamus, brainstem, cerebellum, corpus callosum, anterior cingulate, insula, and subcortical white matter. Gray matter volume at baseline predicted volume recovery during abstinence better than white matter. Drinking severity was not significantly related to brain structural changes assessed with this method. Longitudinally, deformation-based morphometry confirmed tissue recovery in RAs who maintain long-term sobriety. Abstinence-associated tissue volume gains are significant in focal parts of the fronto-ponto-cerebellar circuit that is adversely affected by heavy drinking.

Adult↗
PubMed2006

Non-treatment-seeking heavy drinkers: effects of chronic cigarette smoking on brain structure.

We previously reported [Cardenas, V.A., Studholme, C., Meyerhoff, D.J., Song, E., Weiner, M.W., 2005. Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes. Psychiatry Res. 138, 115-130] that non-treatment-seeking, active heavy drinkers (HD) demonstrated smaller regional neocortical gray matter volumes compared to light drinking controls; however, the potential effects of chronic cigarette smoking on regional brain volumes were not addressed. The goal of this retrospective analysis was to determine if chronic smoking affected brain structure in the non-treatment-seeking heavy drinking sample from our earlier report (i.e., Cardenas et al., 2005). Regional volumetric comparisons were made among age-matched smoking HD (n=17), non-smoking HD (n=16), and non-smoking light drinkers (nsLD; n=20) from our original sample. Quantitative volumetric measures of neocortical gray matter (GM), white matter (WM), subcortical structures, and cerebral spinal fluid (CSF) were derived from high-resolution magnetic resonance imaging. Smoking HD demonstrated smaller volumes than nsLD in the frontal, parietal, temporal GM, and for total neocortical GM. Smoking HD also demonstrated smaller temporal and total GM volumes than non-smoking HD. Non-smoking HD and nsLD did not differ significantly on GM volumes. Further, the three groups did not differ on lobar WM, subcortical structures or regional CSF volumes. These retrospective analyses indicate neocortical GM volume reductions in non-treatment-seeking smoking HD, but not in non-smoking HD, which are consistent with our studies in recently detoxified treatment-seeking alcohol-dependent samples.

Adult↗
PubMed2006

A comparison of neurocognitive function in nonsmoking and chronically smoking short-term abstinent alcoholics.

Approximately 70-90% of individuals in North America seeking treatment for alcoholism are chronic smokers. A growing body of evidence suggests chronic cigarette smoking alone adversely affects neurocognition in adults. However, few studies on the neurocognitive function of short-term abstinent alcoholics have specifically considered the potential effects of chronic cigarette smoking. In this study, 20 nonsmoking recovering alcoholics (nsRA) and 22 actively smoking recovering alcoholics (sRA) participants, matched on age and education, were contrasted on a comprehensive neurocognitive battery after 34+/-9 days of abstinence. nsRA were superior to sRA on measures of auditory-verbal learning and memory, processing speed, cognitive efficiency, and static postural stability. These group differences were not a function of group disparities in age, education, estimated premorbid verbal intelligence, lifetime alcohol consumption, or other measured comorbid psychiatric or medical factors. In sRA, longer smoking duration was negatively correlated with executive skills, visuospatial learning, general cognitive efficiency, and static postural stability. These results indicate that greater consideration of the potential neurobiological effects of current chronic smoking on neurocognitive functioning is warranted in studies of alcoholism and other conditions where smoking is a common comorbid factor.

Adult↗
PubMed2006

Smoking comorbidity in alcoholism: neurobiological and neurocognitive consequences.

Considerable research attests to the adverse effects of chronic smoking on cardiac, pulmonary, and vascular function as well as on increased risk for various cancers. However, comparatively little is known about the effects of chronic smoking on brain function. Although smoking rates have decreased in the developed world (they have increased in the developing world), smoking rates have been at a persistently high level in individuals with alcohol use disorders. Despite the high prevalence of comorbid chronic smoking and alcohol dependence, very few studies have addressed the separate and interactive effects that smoking and alcoholic drinking may have on neurobiology and brain function. This symposium, which took place at the annual meeting of the Research Society on Alcoholism in Santa Barbara, California, on June 29, 2005, postulates that the neurobiologic and neurocognitive abnormalities commonly described in studies of alcohol-dependent individuals are modulated by concurrent abuse of tobacco products and that brain recovery in abstinent alcoholic individuals is affected by chronic smoking. Four expert speakers and a discussant from different research disciplines focus in this symposium on the description of neurobiological and neurobehavioral effects because of concomitant drinking and smoking. Understanding the potential separate effects and interactions of chronic nicotine/smoking and alcohol consumption promotes a better understanding of specific mechanisms and neurocognitive consequences of brain injury and brain recovery with abstinence. The material presented contributes useful information to ongoing discussions about treatment strategies for these comorbid disorders and valuable educational material that can be used to affect public perception about smoking and perhaps health policy.

Alcoholism↗
PubMed2006

Brain metabolite concentrations and neurocognition during short-term recovery from alcohol dependence: Preliminary evidence of the effects of concurrent chronic cigarette smoking.

BACKGROUND: Longitudinal studies of brain tissue metabolite recovery in short-term abstinent alcoholics have primarily investigated the frontal lobes and cerebellum with variable results. Preliminary proton magnetic resonance spectroscopic imaging (1H MRSI) suggested that chronic cigarette smoking exacerbates alcohol-induced brain injury in 1-week abstinent alcoholics. However, the potential effects of chronic cigarette smoking on the recovery of alcohol-induced brain injury have not been studied. METHODS: Multislice short-echo time 1H MRSI was used to measure longitudinal changes in common brain metabolites in 25 recovering alcohol-dependent individuals (RA), retrospectively assigned to smoking (n = 14) and nonsmoking (n = 11) subgroups. Recovering alcohol-dependent individuals in longitudinal analyses were studied after approximately 7 and 34 days of abstinence from alcohol. In cross-sectional analyses, 36 RA (19 smokers, 17 nonsmokers) with approximately 34 days of sobriety were compared with 29 light drinkers (LD). Relationships between neurocognition and metabolite concentrations in abstinent RA were also examined. RESULTS: Over 1 month of abstinence from alcohol, RA, as a group, showed significant increases of regional N-acetylaspartate (NAA; marker of neuronal viability) and choline-containing compounds (Cho; marker of cell membrane synthesis/turnover) primarily in frontal and parietal lobes. These increases appeared to be driven by nonsmoking RA. Cross-sectional results indicate that metabolite levels in RA at 35 days of sobriety are not significantly different from those in LD in most regions, except for lower NAA and Cho in parietal WM and subcortical structures. However, metabolite levels at that time appear to be strongly modulated by smoking status. The patterns of metabolite-neurocognition relationships were different for nonsmoking and smoking RA. CONCLUSIONS: Within the first weeks of sobriety, regional brain NAA and Cho levels increased, but metabolite levels did not normalize in all brain regions after 35 days of sobriety. Neurobiologic recovery in RA appeared to be adversely affected by chronic smoking. Greater consideration of the effects of continued cigarette smoking on the neurobiologic and neurocognitive recovery of alcohol-dependent individuals is warranted.

Adult↗
PubMed2005

Chronic active heavy drinking and family history of problem drinking modulate regional brain tissue volumes.

The goals of this study were to measure if chronic active heavy drinking is associated with brain volume loss in non-treatment seeking men and women, and to assess the effect of positive family history of problem drinking on brain structure in heavy drinkers. Automated image processing was used to analyze high-resolution T1-weighted magnetic resonance images from 49 active heavy drinkers and 49 age- and sex-matched light drinkers, yielding gray matter, white matter and cerebrospinal fluid (CSF) volumes within the frontal, temporal, parietal and occipital lobes. Regional brain volume measures were compared as a function of group, sex and their interaction. Within heavy drinkers, volumes were correlated with measures of alcohol consumption and compared as a function of family history of problem drinking. Deformation morphometry explored localized patterns of atrophy associated with heavy drinking or severity of drinking. We found significant gray matter volume losses, but no white matter losses, in active heavy drinkers compared with light drinkers. Women had greater gray matter and smaller white matter and CSF volumes as a percentage of intracranial vault than men. Within heavy drinkers, smaller gray matter volumes were associated with higher current levels of drinking and older age, while a positive family history of problem drinking was associated with smaller CSF volumes. Community-dwelling heavy drinkers who are not in alcoholism treatment have dose-related gray matter volume losses, and family history of problem drinking ameliorates some structural consequences of heavy drinking.

Adult↗
PubMed2005

Temporal dynamics and determinants of whole brain tissue volume changes during recovery from alcohol dependence.

Brain shrinkage and its partial reversibility with abstinence is a common neuroimaging finding in alcohol dependent individuals. We used an automated three-dimensional whole brain magnetic resonance imaging method (boundary shift integral) in 23 alcohol dependent individuals to measure the temporal dynamics of cerebral tissue and spinal fluid volume changes over a 12-month interval and to examine the major determinants of brain tissue change rates during abstinence and non-abstinence. We found more rapid brain tissue gain during the first month of sobriety than in the following months. The most rapid volume recovery was observed in abstinent individuals with the greatest baseline brain shrinkage and drinking severity. The rapid reversal of brain volume gains in non-abstinent individuals and tissue volume changes are modulated by duration of abstinence and non-abstinence periods, as well as recency of non-abstinence. Age, family history density of alcoholism, relapse severity, and duration or age of onset of heavy drinking were not major determinants of brain shrinkage and brain volume recovery rates. Treatment providers may use this tangible information to reinforce the biomedical benefits of sobriety. Previous quantitative measurements of brain volumes in alcohol dependent individuals performed after several weeks of abstinence likely underestimated the full extent of chronic alcohol-associated brain shrinkage.

Adult↗
PubMed2005

Using automated morphometry to detect associations between ERP latency and structural brain MRI in normal adults.

Despite the clinical significance of event-related potential (ERP) latency abnormalities, little attention has focused on the anatomic substrate of latency variability. Volume conduction models do not identify the anatomy responsible for delayed neural transmission between neural sources. To explore the anatomic substrate of ERP latency variability in normal adults using automated measures derived from magnetic resonance imaging (MRI), ERPs were recorded in the visual three-stimulus oddball task in 59 healthy participants. Latencies of the P3a and P3b components were measured at the vertex. Measures of local anatomic size in the brain were estimated from structural MRI, using tissue segmentation and deformation morphometry. A general linear model was fitted relating latency to measures of local anatomic size, covarying for intracranial vault volume. Longer P3b latencies were related to contractions in thalamus extending superiorly into the corpus callosum, white matter (WM) anterior to the central sulcus on the left and right, left temporal WM, the right anterior limb of the internal capsule extending into the lenticular nucleus, and larger cerebrospinal fluid volumes. There was no evidence for a relationship between gray matter (GM) volumes and P3b latency. Longer P3a latencies were related to contractions in left temporal WM, and left parietal GM and WM near the interhemispheric fissure. P3b latency variability is related chiefly to WM, thalamus, and lenticular nucleus, whereas P3a latency variability is not related as strongly to anatomy. These results imply that the WM connectivity between generators influences P3b latency more than the generators themselves do.

Adult↗
PubMed2005

Heavy alcohol consumption in individuals with HIV infection: effects on neuropsychological performance.

Higher rates of alcohol use have been reported in HIV+ individuals compared to the general population. Both heavy alcohol use and HIV infection are associated with increased risk of neuropsychological (NP) impairment. We examined effects of heavy active alcohol use and HIV on NP functioning in a large sample of community-residing HIV+ individuals and HIV- controls. The four main study groups included 72 HIV- light/non-drinkers, 70 HIV- heavy drinkers (>100 drinks per month), 70 HIV+ light/non-drinkers, and 56 HIV+ heavy drinkers. The heavy drinking group was further subdivided to assess effects of the heaviest levels of active alcohol use (>6 drinks per day) on NP functioning. A comprehensive NP battery was administered. Multivariate analysis of covariance was employed to examine the effect of HIV and alcohol on NP functioning after adjusting for group differences in age and estimated premorbid verbal intellectual functioning. The analyses identified main effects of heavy drinking and HIV on NP function, with greatest effects involving the contrast of HIV+ heavy drinkers and the HIV- light drinkers. Synergistic effects of heaviest current drinking and HIV infection were identified in analyses of motor and visuomotor speed. Supplementary analyses also revealed better NP function in the HIV+ group with antiretroviral treatment (ART) and lower level of viral burden, a finding that was consistent across levels of alcohol consumption. Finally, heavy alcohol use and executive functioning difficulties were associated with lower levels of self-reported medication adherence in the HIV+ group. The findings suggest that active heavy alcohol use and HIV infection have additive adverse effects on NP function, that they may show synergistic effects in circumstances of very heavy active alcohol use, and that heavy drinking and executive functioning may mediate health-related behaviors in HIV disease.

Adult↗
PubMed2005

Health risks of chronic moderate and heavy alcohol consumption: how much is too much?

This article presents the proceedings of a symposium held at the meeting of the International Society for Biomedical Research on Alcoholism (ISBRA) in Mannheim, Germany, in October 2004. Most of what we know about the deleterious effects of alcohol in vivo has been gleaned from studies in sober alcoholics recruited from substance abuse treatment programs. Little is known about effects of chronic drinking in the moderate or heavy range encountered in a much larger fraction of modern society. Extrapolation of information on the adverse effects of chronic drinking on organ function from clinical samples to social drinkers in the general population has to be met with great skepticism, as it may lead to wrong conclusions about the chronic effects of alcohol in social drinkers. Several recent studies suggest that moderate alcohol consumption has certain beneficial health effects, whereas heavy social alcohol consumption has recently been associated with organ abnormalities and cognitive deficits. These social drinking effects have attracted great public interest; reports of benefits of moderate drinking have also inspired inappropriate publications by the media, including misleading advertisements by the alcohol producing and distributing industry. Although adverse effects of moderate to heavy drinking on heart, liver, and cancer development have attracted attention by clinicians and researchers for some time, its compromising effects on brain and cognition have only recently been studied. This symposium brought together researchers from different disciplines, who reviewed and presented new data on consequences of social drinking in the areas of clinical neuropsychology and behavior (Drs. Nixon and Meyerhoff), neurophysiology (Dr. Nixon, Ms. De Bruin), neuroimaging (Ms. de Bruin, Dr. Meyerhoff), hepatic disease (Dr. Bode), and cancer (Dr. Seitz). The symposium aimed to clarify both the potential health benefits of moderate alcohol consumption and risks of moderate and heavy drinking on proper organ function and to provide insights and new data to practicing physicians and public health authorities for education on problem drinking.

Alcohol Drinking↗
PubMed2005

Sensitive and fast T1 mapping based on two inversion recovery images and a reference image.

We developed a fast method to obtain T1 relaxation maps in magnetic resonance imaging (MRI) based on two inversion recovery acquisitions and a reference acquisition, while maintaining high sensitivity by utilizing the full dynamic range of the MRI signal. Optimal inversion times for estimating T1 in the human brain were predicted using standard error propagation theory. In vivo measurements on nine healthy volunteers yielded T1 values of 1094+/-18 ms in gray matter and 746+/-40 ms in white matter, in reasonable agreement with literature values using conventional approaches. The proposed method should be useful for clinical studies because the T1 maps can be obtained within a few seconds.

Algorithms↗
PubMed2004

Magnetic resonance detects brainstem changes in chronic, active heavy drinkers.

Neuropathological and neuroimaging studies show cortical and subcortical volume loss in alcohol-dependent individuals. Using quantitative magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopic imaging ((1)H MRSI), we studied the size and potential cellular injury of the brainstem in untreated heavy alcohol drinkers. The brainstem is considered critical in the development and maintenance of drug and alcohol dependence. Two methods of brainstem size determination were compared: standard volumetry vs. midsagittal MR image area measurement. Heavy drinkers (n=12) and light drinkers (n=10) were compared with MRI; (1)H MRSI brainstem data were obtained from a subset of this cohort. Chronic heavy drinking was associated with significantly smaller midsagittal areas of the brainstem, midbrain, and pons, and with significantly smaller overall brainstem volume. Heavy drinking was also associated with significantly lower ratios of N-acetyl-aspartate and choline-containing metabolites compared with creatine-containing compounds in the brainstem, independent of brainstem atrophy. Additionally, brainstem volume and midsagittal brainstem area were correlated (r=0.78). These structural and metabolite findings are consistent with neuronal injury in the brainstem of untreated chronic heavy drinkers. The results also indicate that the midsagittal MRI brainstem area is an easily determined and reliable indicator of brainstem volume.

Adult↗
PubMed2004

Regional patterns of brain metabolites in AIDS dementia complex.

The relationship of the cellular changes in the HIV-infected brain to the onset and progression of AIDS dementia complex (ADC) remains uncertain. We undertook an in vivo proton magnetic resonance spectroscopy (MRS) study and used factor analysis to identify specific cellular and regional brain changes that may serve as metabolic markers of ADC. The ratio of N-acetyl aspartate (NAA), choline (Cho), and myoinositol (MI) over creatine (Cr), markers of neuronal and glial cell metabolism, were measured in the basal ganglia, centrum semiovale, and parietal cortex from 100 subjects with and without ADC. Three metabolic patterns were identified, which we termed "inflammatory" (mainly MI/Cr elevations in all three regions plus Cho/Cr increases in the centrum semiovale and parietal cortex), "basal ganglia" (mostly NAA/Cr and Cho/Cr elevations in the basal ganglia), and "neuronal" (primarily NAA/Cr reductions in the centrum semiovale and the parietal cortex). Logistic regression analysis revealed that, adjusted for age, basal ganglia and neuronal pattern scores were strongly associated with ADC but inflammatory levels were not. We conclude that by using factor analysis, we are able to combine multiple metabolites across brain regions in a biologically plausible manner and construct a predictive model of ADC adjusting for relevant factors such as age.

AIDS Dementia Complex↗
PubMed2004

Cigarette smoking exacerbates chronic alcohol-induced brain damage: a preliminary metabolite imaging study.

BACKGROUND: Cigarette smoking is common among alcohol-dependent individuals. Nevertheless, previous research has typically not accounted for the potential independent or compounding effects of cigarette smoking on alcohol-induced brain injury and neurocognition. METHODS: Twenty-four 1-week-abstinent recovering alcoholics (RAs; 14 smokers and 10 nonsmokers) in treatment and 26 light-drinking controls (7 smokers and 19 nonsmokers) were compared on measures of common brain metabolites in gray matter and white matter of the major lobes, basal ganglia, midbrain, and cerebellar vermis, obtained via multislice short-echo time proton magnetic resonance spectroscopic imaging. Smoking and nonsmoking RAs were also contrasted on measures of neurocognitive functioning, as well as laboratory markers of drinking severity and nutritional status. RESULTS: Chronic alcohol dependence, independent of smoking, was associated with lower concentrations of frontal N-acetylaspartate (NAA) and frontal choline-containing compounds, as well as lower parietal and thalamic choline. Smoking RAs had lower NAA concentrations in frontal white matter and midbrain and lower midbrain choline than nonsmoking RAs. A four-group analysis of covariance also demonstrated that chronic cigarette smoking was associated with lower midbrain NAA and choline and with lower vermian choline. In smoking RAs, heavier drinking was associated with heavier smoking, which correlated with numerous subcortical metabolite abnormalities. The 1-week-abstinent smoking and nonsmoking RAs did not differ significantly on a brief neurocognitive battery. In smoking RAs, lower cerebellar vermis NAA was associated with poorer visuomotor scanning speed and incidental learning, and in nonsmoking RAs lower vermis NAA was related to poorer visuospatial learning and memory. CONCLUSIONS: These human in vivo proton magnetic resonance spectroscopic imaging findings indicate that chronic cigarette smoking exacerbates chronic alcohol-induced neuronal injury and cell membrane damage in the frontal lobes of RAs and has independent adverse effects on neuronal viability and cell membranes in the midbrain and on cell membranes of the cerebellar vermis. Higher smoking levels are associated with metabolite concentrations in select subcortical structures. Greater consideration of the potential effects of comorbid cigarette smoking on alcohol-induced brain damage and other diseases affecting the central nervous system is warranted.

Adult↗
PubMed2003

Abnormal contingent negative variation in HIV patients receiving antiretroviral therapy.

The contingent negative variation, an event-related potential related to neural activity in the frontal lobe and basal ganglia, neuropsychological tests and structural MRI were used to examine CNS function and structure in HIV-positive patients receiving antiretroviral therapy. Relative to controls, HIV patients had smaller thalamic volume and reduced late contingent negative variation amplitude that correlated with caudal atrophy. Behaviorally, viremic patients were more impaired than virally suppressed patients and controls on neuropsychological measures of psychomotor speed, selective attention and mental flexibility. These results suggest that antiretroviral therapy may not be effective in protecting cortical and subcortical structures against HIV-related neuropathology, regardless of immune function. However, the benefits of antiretroviral therapy on immune function appear to facilitate neurocognitive performance.

Adult↗
PubMed2003

A multi-center 1H MRS study of the AIDS dementia complex: validation and preliminary analysis.

PURPOSE: To demonstrate the technical feasibility and reliability of a multi-center study characterizing regional levels of the brain metabolite ratios choline (Cho)/creatine (Cr) and myoinositol (MI)/Cr, markers of glial cell activity, and N-acetyl aspartate (NAA)/Cr, a marker of mature neurons, in subjects with AIDS dementia complex (ADC). MATERIALS AND METHODS: Using an automated protocol (GE PROBE-P), short echo time spectra (TE = 35 msec) were obtained at eight sites from uniformly prepared phantoms and from three brain regions (frontal white matter, basal ganglia, and parietal cortex) of normal volunteers and ADC and HIV-negative subjects. RESULTS: A random-effects model of the phantom and volunteer data showed no significant inter-site differences. Feasibility of a multi-center study was further validated by detection of significant differences between the metabolite ratios of ADC subjects and HIV-negative controls. ADC subjects exhibited significantly higher Cho/Cr and MI/Cr in the basal ganglia and significantly reduced NAA/Cr and significantly higher MI/Cr in the frontal white matter. These results are consistent with the predominantly subcortical distribution of the pathologic abnormalities associated with ADC. CONCLUSION: This is the first study to ascertain and validate the reliability and reproducibility of a short echo time (1)H-MRS acquisition sequence from multiple brain regions in a multi-center setting. It should now be possible to examine the regional effects of HIV infection in the brain in a large number of subjects and to study the metabolic effects of new therapies for the treatment of ADC in a clinical trial setting.

AIDS Dementia Complex↗
PubMed2003

Indirect imaging of ethanol via magnetization transfer at high and low magnetic fields.

Ethanol (EtOH) is believed to exert its neurochemical effects through interactions with brain cellular components, which causes a fraction of brain EtOH to have a lower molecular mobility. This facilitates magnetization transfer to other molecules similarly associated with macromolecules, such as water. It was hypothesized that this effect can be used in vivo to image EtOH indirectly via the much stronger brain tissue water resonance. EtOH-containing bovine serum albumin samples were used to demonstrate magnetic coupling between EtOH and water at 7 T and 1.5 T. Spectroscopy and imaging experiments demonstrated that EtOH signal saturation yielded greater water signal reduction than inversion and that this reduction scaled with EtOH concentration in the BSA samples. In human brain at physiologically relevant brain EtOH concentrations, water signal reductions were measurable when saturating the EtOH resonance. Strengths and limitations of indirectly imaging brain EtOH are discussed.

Brain↗