Effects of abstinence and relapse upon neuropsychological function and cerebral glucose metabolism in severe chronic alcoholism

Abstract

Prolonged excessive consumption of alcohol has been associated with a variety of cognitive disorders accompanied by neuropathological and neurochemical abnormalities of the brain, particularly in the frontal lobes. Studies with positron emission tomography (PET) have shown decreased local cerebral metabolic rates for glucose (ICMRglc) in frontal regions, with correlated abnormalities on neuropsychological tests sensitive to executive functioning. This investigation was designed as a pilot study to examine the effects of abstinence and relapse in patients with severe chronic alcoholism studied longitudinally with PET and with neuropsychological evaluation to assess both general and executive functioning. Six patients, including 4 who remained relatively abstinent and 2 who relapsed following their initial evaluation, were studied twice, with inter-evaluation intervals ranging from 10 to 32 months. The patients who remained abstinent or who had minimal alcohol use showed partial recovery of ICMRglc in two of three divisions of the frontal lobes and improvement on neuropsychological tests of general cognitive and executive functioning, whereas the patients who relapsed had further declines in these areas. These results, although based upon a relatively small number of subjects, provide preliminary support for at least partial recovery of metabolic and cognitive functioning in individual patients who abstain from alcohol.     

Regional cerebral blood flow and neuropsychological functioning in early and late onset alcoholism

The aim of the study was to compare late and early onset alcoholism with regard to regional cerebral blood flow (rCBF) and neuropsychological functioning. Ten late onset and 13 early onset male alcoholics were included in the study, the criterion being the age of onset for alcohol abuse. Six healthy male volunteers were included as a control group. Regional measures of cortical cerebral blood flow were assessed using Tc-99m-HMPAO single photon emission computed tomography (SPECT) after a detoxification period. When compared with the control group, the early onset group showed reduced relative perfusion in the left superior frontal region, while relative perfusion in the late onset group was deficient in both right and left superior frontal regions. Both groups of alcoholic patients also displayed impairment in frontal lobe functions and non-verbal memory. The results of this study indicate that early onset alcoholism is associated with hypoperfusion in the left superior frontal region while the late onset subtype is characterized by uniformly hypoperfused left and right superior frontal regions. Additionally, both groups of alcoholic patients exhibit an almost identical pattern of neuropsychological abnormalities mainly related to frontal lobe functions and non-verbal memory. Collectively these findings support previous evidence suggesting a key role of frontal lobe pathology in understanding the neurobiology of alcoholism.     

Relationship between CT scan findings and neuropsychological performance in chronic schizophrenia

Studies relating CT abnormalities to impairments on neuropsychological tests in schizophrenic patients are critically reviewed. The overall conclusion is that there appears to be an association between CT abnormalities and neuropsychological deficits in at least some schizophrenic patient samples. It is proposed that there may be two classes of CT abnormalities in schizophrenia: "incidental" versus "essential" CT abnormalities and that neuropsychological impairment above the baseline levels found in most schizophrenic patients may be associated only with the former type. Only attempts to replicate these findings in different schizophrenic samples drawn from different settings can reveal whether this association between CT abnormalities and neuropsychological deficits is widely generalizable.     

Insight,global neuropsychological functioning,and symptomatology in chronic schizophrenia

It is proposed that poor insight in schizophrenia may be explained by neuropsychological dysfunction and linked to the negative syndrome, which in turn may be related to structural neurological impairment. This study tested the hypothesis that poor insight is related to global neuropsychological impairment and negative symptoms in 89 patients with chronic schizophrenia. No significant association was found between total insight and cognitive impairment. When the dimensions of insight-treatment compliance, awareness of illness, and symptom attribution-were analyzed separately, symptom misattribution was modestly correlated with frontal impairment. However, in subsequent multiple regression analyses, cognitive impairment failed to be a significant predictor of this or any other dimension of insight. Symptoms, particularly positive ones, accounted for approximately one quarter of the variance in symptom misattribution and the total insight score. These results suggest that neuropsychological functioning cannot account for the variance in insight, and that only one quarter of the variance in symptom misattribution can be explained by symptomatology. Future research could also address the role of psychosocial factors in modulating the expression of insight.     

Analysis of neuropsychological functioning in patients with chronic fatigue syndrome.

Memory impairment dominates the cognitive complaints of patients with chronic fatigue syndrome (CFS). Twenty CFS patients were available for studies with a clinical and experimental battery composed of memory and cognitive tests. The results on objective testing indicated that the CFS patients had some mild memory impairment, but only on tasks requiring conceptually driven encoding and retrieval processes. There were no associations between the nature of the precipitating illness, self ratings of fatigue, physical findings, or laboratory determination and objective memory performance or self report of memory functioning. These generally negative results indicate that memory impairment in CFS patients is typically mild and involves memory processes that participate in conceptualising information.     

Relationship of neuropsychological status to everyday functioning in healthy and chronically ill persons

Three hundred and three patients with chronic obstructive pulmonary disease and concomitant neuropsychological impairment plus 99 healthy control subjects matched on the basis of socio-demographic variables were administered an expanded version of the Halstead-Reitan Battery and a battery of instruments measuring the quality of everyday-life functioning. The results indicated that neuropsychological measures can be used to predict everyday-life functioning in impaired persons, but few significant relationships were observed in the normals. Neuropsychological status was more consistently related to activities of daily living and basic social role performance than to emotional status. Complex, multifunctional neuropsychological tasks were found to be the best overall predictors of life functioning, whereas more specific tasks served as better predictors of specific dimensions of life functioning.     

Isocapnic hypoxemia and neuropsychological functioning

We evaluated the cognitive effects of hypoxemia independent of hypocapnia in 20 right-handed male subjects using a battery of brief neuropsychological tests. Results of a profile analysis indicated that performance during hypoxia was reliably different for Digit Symbol and Finger Tapping tests. Trend analysis demonstrated a significant linear pattern for Finger Tapping results, such that lower levels of oxygen were associated with slower rates of tapping. No significant trends were observed for Digit Symbol results. The observation of hypoxic effects on Digit Symbol and Finger Tapping tests is consistent with previous findings of neuropsychological changes secondary to hypoxia. The negative results observed for the remaining tests are inconsistent with past literature. It is likely that methodological differences contributed to these discrepancies, including previous reliance on inspired air to index hypoxemia rather than monitoring arterial oxygen saturation directly and failure to control for differences in CO2 levels during induced hypoxia. These variables should be controlled in future research.     

Relationship of neuropsychological status to everyday functioning in healthy and chronically Ill persons

Abstract

Three hundred and three patients with chronic obstructive pulmonary disease and concomitant neuropsychological impairment plus 99 healthy control subjects matched on the basis of socio-demographic variables were administered an expanded version of the Halstead-Reitan Battery and a battery of instruments measuring the quality of everyday-life functioning. The results indicated that neuropsychological measures can be used to predict everyday-life functioning in impaired persons, but few significant relationships were observed in the normals. Neuropsychological status was more consistently related to activities of daily living and basic social role performance than to emotional status. Complex, multifunctional neuropsychological tasks were found to be the best overall predictors of life functioning, whereas more specific tasks served as better predictors of specific dimensions of life functioning.     

Isocapnic hypoxemia and neuropsychological functioning

Abstract

We evaluated the cognitive effects of hypoxemia independent of hypocapnia in 20 right-handed male subjects using a battery of brief neuropsychological tests. Results of a profile analysis indicated that performance during hypoxia was reliably different for Digit Symbol and Finger Tapping tests. Trend analysis demonstrated a significant linear pattern for Finger Tapping results, such that lower levels of oxygen were associated with slower rates of tapping. No significant trends were observed for Digit Symbol results. The observation of hypoxic effects on Digit Symbol and Finger Tapping tests is consistent with previous findings of neuropsychological changes secondary to hypoxia. The negative results observed for the remaining tests are inconsistent with past literature. It is likely that methodological differences contributed to these discrepancies, including previous reliance on inspired air to index hypoxemia rather than monitoring arterial oxygen saturation directly and failure to control for differences in CO₂ levels during induced hypoxia. These variables should be controlled in future research.     

Oral aluminum and neuropsychological functioning

Summary Nine dialysis patients with significantly increased serum-aluminum levels due to chronic ingestion of aluminum hydroxide gels and eleven dialysis patients with normal serum-aluminum levels were tested neuropsychologically for generalized functions (intelligence, reasoning, memory) and for more specific abilities (visual memory, verbal and reading fluency, manual dexterity). All tests did not reveal any significant difference in neuropsychological functioning between the two groups. This finding seems to indicate that oral aluminum is not neurotoxic for man, even under circumstance of renal failure. This contradicts the idea that oral aluminum plays a role in the etiology of dialysis dementia. However, the possibility cannot be excluded that aluminum overload in the present sample was not sufficient to induce changes in CNS functioning. Thus, until the importance of oral aluminum has been decided, it seems wise to keep all sources of aluminum overload as low as possible.Part of this investigation was presented at the XVI EDTA Congress, Amsterdam, June 1979, and at the XXI Congress of the Italian Society of Neurology, Catania, November 1979     

Relationship between psychopathology and cognitive functioning in schizophrenia

The purpose of this study was to delineate the relationship between positive, negative, cognitive, depressive, and excitement symptom dimensions of schizophrenia and cognitive functioning. Fifty-eight patients with schizophrenia (DSM-IV criteria) were assessed using the Positive and Negative Syndrome Scale (PANSS) and a battery of neuropsychological tests (executive function/abstraction, verbal and spatial working memory, verbal and nonverbal memory/learning, attention, visuospatial ability, and psychomotor speed). The cognitive symptom dimension correlated with executive functions, attention, verbal memory, and spatial ability. Severity of the negative symptom dimension was related to impairment in the structure of the semantic knowledge system, verbal memory, and auditory attention. In contrast, severity of the positive symptom dimension correlated only with impairment in the structure of the semantic knowledge system, and psychomotor speed. Finally, severity of the depressive and excitement symptom dimension was not associated with cognition. Correlations between symptom dimensions and cognitive measures were at best modest. Severity of cognitive and negative symptoms was mainly correlated with deficits on executive functions, semantic memory, and verbal memory, while positive symptoms only with semantic memory. These correlations were modest, suggesting that psychopathology and cognitive deficits in schizophrenia are caused, at least partially, by distinct pathophysiological processes.     

The relationship between alcoholic cerebellar degeneration and cognitive and emotional functioning

Although it is now widely acknowledged that the cerebellum contributes to the modulation of higher-order cognitive and emotional functions, this relationship has not been extensively explored in perhaps the largest group of individuals with cerebellar damage, chronic alcoholics. Localised damage to the cerebellum has been associated with a specific constellation of deficits and has been termed the 'cerebellar cognitive affective syndrome' (CCAS) [Schmahmann, J.D., Sherman, J.C., 1998. The cerebellar cognitive affective syndrome. Brain 121, 561-579]. The CCAS describes a profile of impairments, including deficits in executive functioning and visuospatial skills, language disruption and altered personality and affective behaviour. It is conceivable that the CCAS may also develop in a subgroup of alcoholics with alcoholic cerebellar degeneration and may in part account for a proportion of the cognitive and affective deficits commonly observed with the condition. While evidence has emerged supporting such a relationship, methodological limitations and the lack of theoretically driven investigation of the contribution of cerebellar dysfunction to cognitive and emotional functioning in chronic alcoholics, preclude definitive conclusions being drawn.     

Changes in neuropsychological performance during treatment for alcoholism

A battery of 24 neuropsychological tests was administered to drug-free alcoholic inpatients (n = 91) within 7 days of their last drink and again 17 days later. Comparisons between this group and a nonalcoholic group of medical inpatients (n = 20) also given the same test battery twice indicated very little improvement due to abstinence (short-term improvement) in the alcoholics after controlling for practice effects. Similarly, when early postwithdrawal performance of the alcoholics was compared to an alcoholic control group (n = 32), which took the test battery only once 21 days after their last drink, little evidence for short-term recovery of cognitive functions was obtained. Insofar as decisions about the initiation of therapeutic treatments which rely on cognitive processes are based on neuropsychological performance, we conclude that such treatments may commence as soon as the clinical symptoms associated with acute withdrawal have subsided.     

Relationship between functional and neuropsychological performance in early Alzheimer disease

Twenty-four subjects with Alzheimer disease underwent cognitive and functional assessment. Functional assessment by caregivers consisted of a 25-item bipolar analog scale measuring activities of daily living and social behaviors divided into four functional domains: memory, attention/executive abilities, everyday skills, and self-care. Cognitive assessment consisted of standardized neuropsychological tests designed to evaluate five cognitive domains: episodic memory, attention/executive function, semantic memory, visuospatial function, and auditory-verbal short-term (working) memory. Functional assessment correlated well with overall severity as measured by Mini Mental State Examination (r = -0.733). Analysis of individual cognitive and functional domains revealed no significant correlation between episodic memory and functional performance. By contrast, functional ability correlated strongly with the cognitive domains of visuospatial function and semantic memory, being significantly greater than the correlation of functional ability with any other cognitive domain. These results were supported by multiple regression analyses that showed visuospatial function to be the sole cognitive predictor of functional abilities. These findings have implications for the evaluation of drug therapies in Alzheimer disease, in particular the effect of current cholinergic therapies on activities of daily living.     

Relationship between EEG reactivity and neuropsychological tests in vascular dementia

Summary 17 patients with vascular dementia (VaD) representing moderate to severe stage of the disease and 11 age-matched control subjects were examined with spectral analysis of EEG and a neuropsychological test battery comprising visual, praxic, verbal and memory functions as well as Mini-Mental Status test. VaD patients did not have less activity in the alpha band than control subjects, but the alpha amplitude ratio between eyes closed (EC) and eyes open (EO) situations (EC/EO ratio) was decreased in VaD patients, compared to controls. In VaD the variables of the awake background EEG with eyes closed (amplitude of alpha, beta, theta and delta activity; mean frequency) had only a few correlations to neuropsychological test scores. However, the (EC)/(EO) alpha ratio showed significant correlations with several neuropsychological variables in the temporo-occipital and centroparietal derivations and some of these correlations were lateralized to the left or right hemisphere. Frontal EEG derivations with less alpha activity did not reveal any correlations to neuropsychological variables. We conclude that the dynamic EC/EO alpha ratio variable may be even more sensitive in the assessment of brain dysfunction in VaD than the background EEG variables.     

Longitudinal study of neuropsychological functioning in patients on chronic hemodialysis: A preliminary report

This study is part of a five-year project to investigate the long term effects of chronic hemodialysis on patients with end-stage renal failure. Previous research has associated hemodialysis with progressive dialysis encephalopathy (PDE), which is characterized by speech disturbances, cognitive impairment, myoclonus and behavioral changes. Little is known about the cause or the course of this syndrome except that is begins 14–36 months after treatment onset and usually culminates in death. The purpose of this study was to investigate neuropsychological (cognitive and behavioral) functioning in dialysis patients over a period of years. To date, 34 patients have been studied for 22 months utilizing a cross-sectional method comparing patients at different stages of treatment combined with a longitudinal method of repeated evaluations over time. Current findings show improved cognitive functioning during at least the first year of treatment and no evidence of cognitive deterioration in patients on dialysis for more than one year (M = 4.3). These findings offer strong evidence that PDE is not necessarily a general phenomenon among patients on chronic hemodialysis.     

Chronic low-level mercury exposure and neuropsychological functioning

To measure the effects of chronic low-level exposure to inorganic mercury, the neuropsychological performances of 13 female dental auxiliary workers with elevated head mercury levels (as measured by an X-ray fluorescence technique) were compared with 13 workers with no measurable mercury levels. Workers with elevated mercury levels scored significantly less well on the Recurrent Figures, and SCL-90-R, but not on the WAIS, Rey's AVL, PASAT, BGT, Grooved Pegboard, and Finger Tapping tests. Chronic subtoxic levels of inorganic mercury appear to produce mild changes in short-term nonverbal recall and heightened distress generally, and particularly in categories of obsessive compulsion, anxiety and psychoticism, without alterations in general intellectual functioning, attention, verbal recall, and motor skills.     

The relationship between sleep problems and neuropsychological functioning in children with first recognized seizures

Epilepsy is associated with sleep disturbance, but little is known about how early this relationship develops and how it affects neuropsychological functioning. This study documented the frequency and types of sleep problems and examined how sleep problems are associated with seizures and neuropsychological functioning in 332 children following their first recognized seizure (ages 6–14) and in 225 sibling controls. Formal neuropsychological batteries were administered to all subjects. Sleep was measured using the Sleep Behavior Questionnaire and the Child Behavior Checklist. Sleep problems were more frequent in the seizure sample relative to siblings and previously published norms; bedtime difficulties, daytime somnolence, and parasomnias were the most frequently occurring sleep problems. In the seizure group, sleep problems were related to seizure parameters and to neuropsychological functioning. Seizure patients with significant sleep problems had worse neuropsychological functioning on all measures. Findings demonstrate the significant impact of sleep disturbance on children with newly recognized seizures.