Changes in analogical reasoning in adulthood

This study sought to investigate adult intellectual development through an analysis of a particular type of cognitive ability, verbal analogical reasoning. The performance of 60 individuals between the ages of 20 and 79 was compared on 100 verbal analogies. The subjects consisted of six groups of ten individuals each (five males and five females), matched as a group for education and gender. Solution times and error rates served as the dependent measures. Results showed that there was a significant trend for the older subjects (60- and 70-year-olds) to be slower than the young subjects (20-, 30-, 40-, and 50-year-olds), but not necessarily more error prone. These data suggest that verbal analogical reasoning changes with age. Supplemental data demonstrated a change in other abilities as well (i.e., decline in perceptual-motor speed and spatial skill).     

Imaging of Language-Related Brain Regions in Detoxified Alcoholics

Background:  Neuroimaging studies showed clear evidence of alcoholism-related damage to the frontal lobes and cerebellum. Although these regions have been involved in language processing, language skills are relatively spared in alcoholics. Here, we aimed at identifying neural substrates associated with the preserved mechanisms of language processing in alcoholics. We hypothesized that alcoholics would show a different pattern of neural activity compared with the controls.
Methods:  Alcoholic and nonalcoholic subjects performed an auditory language task while receiving a functional magnetic resonance imaging (fMRI) scan in a 1.5 T magnet. This task has been previously shown to solicit the comprehension processing in healthy controls, with reliable fMRI response in the left frontal and temporal/parietal lobes.
Results:  Behavioral results showed comparable performance (error rates, response time) between the alcoholics and the matched controls. However, analysis of the functional data revealed that the alcoholics exhibited greater fMRI response in the left middle frontal gyrus (pars triangularis), the right superior frontal gyrus, and the cerebellar vermis relative to the controls.
Conclusions:  These findings suggest that frontocerebellar neural activity, supporting the comprehension processing of the auditory language task, may require compensatory mechanisms in alcoholics in order to maintain the same level of performance as the controls.     

Motor Performance in Detoxified Alcoholics

Detoxified male and female alcoholics (aged 20-49 years) and age-matched controls performed a series of 15-sec target-tapping tasks in which they alternatively marked two target strips with a felt marker as rapidly and as accurately as possible. Consistent with "Fitts' Law" (Fitts PM: J Exp Psych 47:381-391, 1954), a highly linear relationship between movement time and task difficulty was observed in all four groups. Overall, the alcoholics were slower and made more errors than the controls, although the pattern of deficit differed for males and females. Accuracy, but not speed, was impaired in male alcoholics. The production of undershoot errors was increased more in alcoholics than nonalcoholics in targets of narrower width, whereas the production of overshoot errors was increased more in alcoholics as target separation decreased. Female alcoholics displayed impairment in speed of movement, but not accuracy. However, both alcoholic groups displayed elevated error rates for the more difficult targets. It is thus possible that detoxified alcoholics might mimic the speed functions of nonalcoholic individuals at the occasional cost of an erroneous response at a difficult target.     

Studies of Alpha-2-Adrenoceptor Function in Abstinent Alcoholics

Hormonal, haemodynamic and subjective psychological responses to the intravenous infusion of clonidine were investigated in nine male alcoholics who had been abstinent for 5 weeks, and were compared with those of nine healthy controls. The growth hormone response to clonidine was significantly blunted in the abstinent alcoholics. Both baseline cortisol levels and the clonidine-induced cortisol decrease were significantly greater in the alcoholics than in controls. Blood pressure, pulse rate and psychological responses to clonidine were similar in both groups. These results indicate that some aspects of alpha-2-adrenoceptor sensitivity are persistently abnormal in alcoholics at least 5 weeks into abstinence.     

Regional Cerebral Metabolism in Female Alcoholics of Moderate Severity Does Not Differ From That of Controls

It is generally believed that women are more vulnerable to alcohol's toxic effects than men. Studies in male alcoholics have consistently shown reductions in brain glucose metabolism. However, such studies have not been done in female alcoholics. The purpose of this study was to evaluate if similar or worse brain metabolic abnormalities occurred in female alcoholics. For this purpose, we measured regional brain metabolism with positron emission tomography and [¹⁸F]fluorodeoxyglucose in 10 recently detoxified female alcoholics and compared it with that in 12 age-matched female controls. There were no differences between alcoholics and control females in regional brain glucose metabolism whether we used regions of interest analysis or statistical parameter maps methods. These results do not support a higher toxicity for the effects of alcohol in the female brain, as assessed with regional brain glucose metabolism, because metabolic values in female alcoholics did not differ from those of controls, whereas metabolic values in male alcoholics are generally lower than those in controls. However, this study is confounded by the fact that the severity of alcohol use in these female alcoholics was less than that of the male alcoholics previously investigated in positron emission tomography studies. Future studies in male subjects with alcoholism of moderate severity are required to address gender differences in sensitivity to alcohol effects in brain metabolism.     

Alcoholism scales of the MMPI: contributions and future directions.

Though MMPI alcoholism scales have been constructed to provide objective information for making alcoholism diagnoses, they have not met with general acceptance. Research has been criticized since alcoholics were not clearly defined and were not subdivided into homogeneous categories. Prealcoholics were not studied and no consistent findings emerged. The present review of alcoholics and prealcoholics indicates that some scales, such as the MacAndrew, are consistent in discriminating alcoholics from controls even when alcoholics were not subdivided into homogeneous categories. These findings suggest that alcoholics have personality characteristics that distinguish them from other groups and provide psychometric justification for alcoholism diagnoses.     

Elevated Plasma Homocysteine in Alcoholics

A significantly higher concentration of plasma homocysteine compared with controls was noted in a group of alcoholics ( n = 42) hospitalized for detoxication. Normal concentrations of plasma homocysteine were reached within 1 or 2 weeks after admission to the hospital. In another group of abstinent alcoholics ( n = 16) plasma homocysteine did not deviate from that of controls. Since hyperhomocysteinemia has been associated with premature vascular disease, we speculate that the increased plasma homocysteine in alcoholics might cause the increased incidence of stroke found in these patients.     

Alcohol Dependence and Responsivity to an Ethanol Stimulus as Predictors of Alcohol Consumption*

Withdrawal symptoms during the previous 30 days were examined in relation to psychophysiological arousal, desire to drink, and operant behavior associated with alcohol consumption. The subjects were 16 male alcoholic patients and 16 control subjects that had been randomly assigned to either an alcohol or placebo condition. Alcoholics showed a greater desire to drink than their respective controls. There was also a significant correlation between autonomic arousal and desire to drink among alcoholics but not controls. There was some evidence that arousal was related to alcohol dependence among alcoholics. Placebo responding among alcoholics was also related to alcohol dependence. Of particular significance was that desire to drink, withdrawal symptomatology, and heart rate accounted for over 57% of the variance in predicting which alcoholics would choose the drink reward following the operant task. These results support the notion that disposition to drink in alcoholics should be examined in a multivariate context.     

Regional Brain Metabolic Response to Lorazepam in Alcoholics during Early and Late Alcohol Detoxification

Changes in GABA function have been postulated to be involved in alcohol tolerance, withdrawal and addiction. In this study we measured regional brain metabolic responses to lorazepam, to indirectly assess GABA function (benzodiazepines facilitate GABAergic neurotransmission), in alcoholics during early and late withdrawal. Brain metabolism was measured using PET and 2-deoxy-2[¹⁸F]fluoro-D-glucose after placebo (baseline) and after lorazepam (30 μg/kg intravenously) in 10 alcoholics and 16 controls. In the alcoholics evaluations were performed 2 to 3 weeks after detoxification and were repeated 6 to 8 weeks later. Controls were also evaluated twice at a 6 to 8 weeks interval. While during the initial evaluation metabolism was significantly lower for most brain regions in the alcoholics than in controls in the repeated evaluation the only significant differences were in cingulate and orbitofrontal cortex. Lorazepam-induced decrements in metabolism did not change with protracted alcohol withdrawal and the magnitude of these changes were similar in controls and alcoholics except for a trend towards a blunted response to lorazepam in orbitofrontal cortex in alcoholics during the second evaluation. Abnormalities in orbitofrontal cortex and cingulate gyms in alcoholics are unlikely to be due to withdrawal since they persist 8 to 11 weeks after detoxification. The fact that there was only a trend of significance for an abnormal response to lorazepam in orbitofrontal cortex indicates that mechanisms other than GABA are involved in the brain metabolic abnormalities observed in alcoholic subjects.     

Systolic Blood Pressure and Neuropsychological Test Performance of Alcoholics

This study examined resting systolic blood pressure (SBP) as a mediator of neuropsychological (NP) test performance in nonhypertensive alcoholics and controls. A median-split was used to assign alcoholics and controls to low and high SBP groups. Results showed that: (1) When SBP level was not considered, alcoholics only performed worse than controls on the WAIS Comprehension subtest. (2) Alcoholics and controls in the high SBP groups had fewer correct items on the WAIS Comprehension and Raven's, Set I tests than subjects in the low SBP groups. (3) Significant Diagnostic Group by SBP Group interaction was found for the Sentence Writing test. For this test only controls in the High SBP Group did worse than controls in the Low SBP Group. (4) Individual group comparisons for all NP tests showed that alcoholics in the High SBP Group were more impaired than controls in the Low SBP Group on the WAIS Comprehension, Shipley Abstraction Age and Stark Visual-Spatial tests; but alcoholics in the Low SBP Group did not differ from, or outperformed, controls in the High SBP Group on the WAIS Comprehension, Shipley Abstraction Age, Raven's, Set I, and Stark Visual-Spatial tests. These data demonstrate that both alcoholism and high SBP adversely and differentially affect the NP test performance of alcoholics and controls.     

Motor functioning and alcohol dependence

BACKGROUND: Autopsy and neuroimaging research in stably abstinent alcoholics illuminated structural and functional abnormalities in brain areas that organize and coordinate motor functioning. Researchers that used behavioural tasks to measure motor functioning found that abstinent alcoholics perform worse than healthy controls. These researchers however did not analyze timed responses into their cognitive and motor components. They thus were unable to decide which aspects of information processing are impaired. We here used a Fitts' task to examine differences in cognitive and motor components between abstinent alcoholics and healthy controls. METHODS: Fifty-two abstinent alcoholics and 52 healthy controls participated in this research design. Fine motor functioning was assessed by means of the Fitts' task. RESULTS: Abstinent alcoholics needed more time to perform timed responses than healthy controls. As both reaction and movement times were higher in abstinent alcoholics, both cognitive and motor processes seem to be impaired. When the task became more difficult (small targets instead of large targets) abstinent alcoholics needed proportionally more time to give the correct response than healthy controls. This phenomenon solely applied to movement times. CONCLUSIONS: These research data indicate that abstinent alcoholics are somewhat impaired on a behavioral level. The execution of timed responses indeed was lengthier in abstinent alcoholics than in healthy controls. As both cognitive and motor processes were impaired, we here assume that both central and peripheral processes are affected by progressive alcohol intake. Abstinent alcoholics also have more difficulties to adapt their motor responses to changing task conditions.     

Association Study Between the 441C Ins/Del and TaqI A Polymorphisms of the Dopamine D2 Receptor Gene and Alcoholism

Dopamine D2 receptors have been implicated in the biology of alcohol preference. We examined the-141 C Ins/Del polymorphism in the promoter region of the dopamine D2 receptor gene (DRD2) and the DRD2 Taql A polymorphisms in 209 Japanese alcoholics and 152 age- and sex-matched Japanese controls. The Ins allele was significantly increased in the alcoholics, compared with the controls ( p < 0.002, odds ratio = 1.82). The Taql A1 allele tended to be more frequent in the alcoholics than in the controls ( p < 0.04). Linkage disequilibrium between these two polymorphisms was weak (a maximum δ value = 0.13). The -141 C Ins/Del polymorphism may affect the vulnerability for alcoholism presumably through different expression of DRD2 in the Japanese.     

Effect of 4-Methylpyrazole on ethanol elimination rate and hepatic redox changes in alcoholics with adequate or inadequate nutrition and in nonalcoholic controls

Ethanol elimination rates produced by chronic alcohol consumption were higher in chronic alcoholics with adequate nutrition than in alcoholics with inadequate nutrition. 4-Methylpyrazole (4-MP, an inhibitor of alcohol dehydrogenase, ADH) at a dose of 7 mg/kg body weight inhibited ethanol elimination by 29% in nonalcoholic controls and by 35% in alcoholics with adequate nutrition, but only by 19% in alcoholics with inadequate nutrition. Galactose elimination rate (which is inhibited by NADH during ethanol oxidation) appeared to be a more sensitive indicator of hepatic redox changes than the lactate/pyruvate ratio of the peripheral venous blood. Ethanol-induced inhibition of galactose elimination was reduced in alcoholics as compared to nonalcoholic controls, and it was more reduced in alcoholics with poor nutrition than in alcoholics with adequate nutrition. Both in controls and in alcoholics, 4-MP reduced the inhibitory effect of ethanol on galactose elimination. In alcoholics with inadequate adequate nutrition, however, the further effect of 4-MP in this respect was negligible. The results indicate that the NADH reoxidation rate in chronic alcoholics is increased and support the existence, in chronic alcoholics with inadequate nutrition, of a non-ADH pathway for ethanol that does not produce reducing equivalents. In alcoholics with inadequate nutrition the proportional contribution of the ADH pathway to total ethanol elimination appears to be more decreased, resulting in reduction of the redox-mediated acute metabolic effects of alcohol.     

Mammillary Body and Cerebellar Shrinkage in Chronic Alcoholics with and without Amnesia

Mammillary body and cerebellar atrophy have been described as postmortem neuropathologic markers of Korsakoff's syndrome. This study examined whether shrinkage in the mammillary bodies and cerebellum is present consistently in amnesic chronic alcoholics during lie and whether the degree of abnormality in these patients differs from that in nonamnesic alcoholics and healthy controls. The severity of shrinkage in the mammillary bodies, cerebellar hemispheres, and cerebellar vermis visualizable on MRI scans was rated on a three-point scale in 33 chronic nonamnesic alcoholics, 9 amnesic alcoholics, and 20 healthy controls. Although both alcoholic groups showed significant mammillary body and cerebellar shrinkage relative to controls, the two patient groups did not differ from each other. Furthermore, four of eight amnesic patients in our sample did not demonstrate clinically significant mammillary body atrophy. These results suggest that alcoholism is associated with mammillary body and cerebellar tissue volume loss but do not provide evidence that these markers distinguish accurately between amnesic and nonamnesic patients. In addition, they suggest that visualizable mammillary body atrophy is not necessary for the development of amnesia in alcoholic patients.     

Host response to mycobacterial infection in the alcoholic rat

Animals, chronically treated with alcohol, were inoculated with mycobacteria (bacillus Calmette-Guérin, 10.2 x 10(6) organisms) into the spleen to produce a granulomatous hepatitis. Before infection, chronic alcohol ingestion was associated with a depressed skin test response to phytohemagglutinin, 71.7% of baseline (P = 0.009). Mycobacterial (bacillus Calmette-Guérin) infection stimulated phytohemagglutinin skin test response to 417% of baseline in controls and 299% in alcoholics (P less than 0.001). The hepatic granuloma response was altered with smaller but more numerous granulomas (mean +/- SEM, 81.2 +/- 1.5 microns2 of area with a frequency of 1.8 granulomas per field in alcoholics vs. 129.8 +/- 5.71 microns2 and 1.2 granulomas per field in controls; P less than 0.001). These changes were associated with a 10-fold increase in colony-forming units per gram of liver (54.5 +/- 18.2 in alcoholics vs. 5.6 +/- 1.83 in controls; P = 0.0006). This model offers precise parameters for host response to infection and indicates that alcohol significantly impairs the clearing capacity for mycobacteria from the liver.     

The Role of Cirrhosis in Memory Functioning of Alcoholics

The effects of alcoholism and liver disease on memory functioning in alcoholics were studied by comparing four groups: normal healthy controls, alcoholics without liver disease, alcoholics with biopsy-confirmed cirrhosis, and nonalcoholics with postnecrotic cirrhosis. Memory capacity was evaluated employing the Benton Visual Retention Test (BVRT), the Rey-Osterreith Complex Figure Test, Digit Span, and the Brown Peterson four-word short-term memory test. A 2 x 2 ANOVA revealed significant main effects for both alcohol and cirrhosis on Digits Forward and the total score on the Brown Peterson test. Additionally, there were significant main effects for cirrhosis on the BVRT. The Brown Peterson test was analyzed using a repeated measures 2 x 2 ANOVA. Significant effects for cirrhosis were observed at all three interpolation periods. The effects for alcohol approached significance at the 30-sec (most difficult) interpolation period. Analysis of error patterns on the Brown Peterson test indicated that overall omission errors were most commonly made among all groups. Significant effects were found for alcohol on omissions and intrusion, while the cirrhosis factor yielded significant effects for phonemic, perseverative, and omission errors. This study demonstrates the importance of liver disease underlying the etiology of memory impairments in alcoholics. The results confirm our earlier findings that neuropsychologic deficits seen in alcoholics may be the result of the combination of alcohol abuse and liver disease.     

Gastric Emptying of Solid Meal in Male Chronic Alcoholics

Nausea and vomiting are common complaints in chronic alcoholics. Autonomic neuropathy and esophageal motor abnormalities are frequently observed in chronic alcoholics, but gastric emptying has not been studied in these patients. Gastric emptying of a solid meal was measured, using 99mTc-sulfur colloid cooked in a scrambled egg, in 10 male chronic alcoholics with upper gastrointestinal complaints of nausea and vomiting. All patients were adequately nourished, recently drinking, but just over withdrawal and free of clinical peripheral neuropathy. Gastric emptying in 10 alcoholics was similar to 5 normal controls (t 1/2 115 +/- 12 versus 107 +/- 8 min). These data suggest that upper gastrointestinal symptoms in chronic alcoholics are not related to gastric motor dysfunction.     

Effects of Alcoholism and Instructional Conditions on Speed/Accuracy Tradeoffs

The speed and accuracy of neuropsychological performance in alcoholics and nonalcoholics were assessed for each item within a four-test computerized battery. Subjects were randomly assigned to one of three instructional conditions: Speed-emphasis instructions, Accuracy-emphasis instructions, or Typical instructions emphasizing speed and accuracy equally. Across conditions, alcoholics were less accurate and took longer to perform than controls. Examining speed and accuracy components separately within each condition, as predicted, the greatest differences in accuracy scores between alcoholics and controls appeared in the Speed-emphasis condition, while the greatest group differences in speed scores appeared in the Accuracy-emphasis condition. The results indicate that the relationships between speed and accuracy are dissimilar between alcoholics and controls; alcoholics exhibit speed/accuracy tradeoffs in that they are unable to adjust performance to meet speed or accuracy demand without suffering substantial compromise in the other aspect of performance. These results have implications for future studies concerning methodological approaches to speed and accuracy assessment and provide support for an information-processing deficit associated with chronic alcohol abuse.     

Corpus Callosal Thickness in Alcoholics

The coronal thickness of the corpus callosum in alcoholics and age- and sex-matched controls was measured in a postmortem study. The alcoholics were found to have a significantly (p <0.001) reduced corpus callosal thickness (3.19 mm) when compared to the controls (4.02 mm). This adds weight to the previous pathological finding of reduced white matter volume in alcoholics, which presumably correlates with brain shrinkage seen on CT scans. A significant linear relationship exists between age and the corpus callosal thickness in controls and the white matter volume and corpus callosal thickness in alcoholics.