Separating cognitive impairment in neurologically asymptomatic alcoholism from Wernicke-Korsakoff syndrome: is the neuropsychological distinction justified?

Recent studies that have combined neuropathological data and clinical histories in a retrospective fashion have shown that Wernicke-Korsakoff neuropathology is often unsuspected antemortem and that, in terms of clinical presentation, it is more heterogeneous than previously assumed. Thus, many studies of neurologically normal alcoholics may have been confounded by the inclusion of patients with neurologically asymptomatic Wernicke-Korsakoff neuropathology. Postmortem and in vivo studies have shown that alcoholics, irrespective of neurological diagnosis, have widespread pathology involving many cortical and subcortical sites. In addition, clinical studies have indicated that, like neurologically asymptomatic alcoholics, alcoholic Korsakoff patients may enjoy substantial recovery in cognitive function. Furthermore, the common research strategy of identifying a subset of neurologically diagnosed Wernicke-Korsakoff syndrome as a discrete group of "pure" Korsakoff's amnesia by using a definitional IQ-Wechsler Memory Scale quotient difference may have created a neuropsychological stereotype that is not representative of the broader clinical group. In light of these considerations, the separate treatment of cognitive impairment in groups of alcoholics distinguished by the clinical signs of Wernicke-Korsakoff syndrome may not be justified.     

Spatial Location Memory in Amnesia: Binding Item and Location Information Under Incidental and Intentional Encoding Conditions

Items located within an array were presented to alcoholic Korsakoff and nonalcoholic mixed-etiology amnesics and to alcoholic and normal controls. Recognition memory for the locations of items was tested after incidental and intentional encoding. When equated on item recognition, neither Korsakoff amnesics nor alcoholic controls benefited from intentional, relative to incidental, encoding instructions. Furthermore, Korsakoff amnesics showed neither disproportionately impaired incidental nor intentional location recognition memory relative to alcoholic controls. In contrast, mixed-etiology amnesics profited significantly from intentional location acquisition relative to incidental instructions, and were impaired somewhat in incidental, but not intentional, location memory relative to normal controls. We discuss these data in relation to Mayes' (1992) contextual memory deficit hypothesis and Hirst's (1982) automatic encoding deficit account, and propose an alternative framework in which the location memory deficit observed in mixed-etiology amnesics is interpreted as a disruption to the ability to bind item and location information.     

Neuropsychological correlates of Greek alcoholic patients who report memory disturbances

We studied 40 male and 37 female (M age=63 yr.) Greek alcoholic patients and an equal number of control subjects. Both groups were evaluated with the Mini-Mental State Examination, the Syndrome Short Test, the Verbal Fluency Test (Category & Letter), the Clock Test, and the Digit Span (Forward and Backward from the Wechsler Adult Intelligence Scale-Revised). Alcoholic patients had statistically significant lower scores on MMSE, Verbal Fluency Test, and Digit Span, and higher scores on the Syndrome Short Test, while positive correlations were found among MMSE, Verbal Fluency Test, Clock Test, Digit Span-Backward, and age. These findings point to frontal lobe dysfunction in Greek alcoholic patients which is not different from that shown in patients from diverse ethnic and cultural backgrounds.     

Alcoholic intoxication and memory storage dynamics

Strength retention functions were obtained for English words from 2 min to 50 min within a continuous recognition memory session and from I to 14 days subsequent to the session, with subjects being sober or moderately intoxicated. A small, but significant, decrement was obtained in memory performance under alcoholic intoxication. However, there was no difference in forgetting rate either within the continuous session or over the subsequent 1- to 14-day period. Single-trace fragility theory provided an excellent fit to the data. The entire effect of alcoholic intoxication was on degree of learning with no effect on the form of the retention function or rate of forgetting. No state-dependent retrieval effects were obtained. White noise during learning and/or retrieval had no effect on acquisition, storage, or retrrieval.     

Incidence of Savant Syndrome in Finland

The general incidence of Savant Syndrome was assessed in Finland. First, a survey was made of all 583 facilities which served people with mental retardation. Second, letters asking for information regarding people with Savant Syndrome were published in two key Finnish journals of the field. We received reports of 45 cases of Savant Syndrome. This makes an incidence rate of 1.4 per 1,000 people with mental retardation. The most common form of exceptional skills was calendar calculation, followed by feats of memory.     

Mechanisms of verbal memory impairment in four neurodevelopmental disorders

Profiles of verbal learning and memory performance were compared for typically developing children and for four developmental disorders characterized by different patterns of language functioning: specific language impairment, early focal brain damage, Williams Syndrome, and Down Syndrome. A list-learning task was used that allowed a detailed examination of the process of verbal learning, recall, and recognition (California Verbal Learning Test--Children's Version). Distinct patterns of performance characterized the four disorders. These patterns were consistent with the language deficits typically seen in the disorders, with the exception of a dissociation seen in Williams Syndrome.     

Strategic and automatic priming of semantic memory in alcoholic Korsakoff patients

To examine whether the organization of semantic memory is intact in alcoholic Korsakoff patients, three semantic memory tasks which do not require active search for stored information were administered to a group of Korsakoff patients and alcoholic controls. The first two tasks used a perceptual identification paradigm in which patients had to identify briefly presented targets preceded by associatively (experiment 1) or categorically (experiment 2) related primes. On both tasks, Korsakoff patients demonstrated intact priming effects. Because priming in these tasks was thought to reflect the operation of strategic processes, experiment 3 was designed to assess automatic spreading activation using a lexical decision task. Here as well, Korsakoff patients demonstrated intact priming. Taken together, these results support the view that the organization of semantic memory in Korsakoff patients has not been disrupted by their brain injury. The implications of these findings for understanding Korsakoff patients' impaired performance on semantic search tasks are discussed.     

Neuropsychological findings in two children diagnosed with hamartoses: evidence of a NLD phenotypic profile.

Hamartoses (HM) are defined as disorders involving nonneoplastic tissue overgrowth. Studies have examined the neuropsychological profiles of children with common HM, such as neurofibromatosis type 1. Limited information is known regarding neuropsychological profiles of rare HM such as Osteochondromatosis Syndrome (OS) and Klippel-Trenaunay Syndrome (KTS). The current investigation is, to our knowledge, the first attempt to define the cognitive phenotypes in two boys with OS and KTS. Results revealed significantly greater impairments involving sensorimotor and visuospatial skills, while verbal memory and language skills appeared relatively preserved. Significant neurobehavioral problems and marked social difficulties were evident. These findings suggest that these syndromes are on a Nonverbal Learning Disorder (NLD) continuum, with varying degrees of severity.     

Neuropsychological Findings in Two Children Diagnosed with Hamartoses: Evidence of a NLD Phenotypic Profile

Hamartoses (HM) are defined as disorders involving nonneoplastic tissue overgrowth. Studies have examined the neuropsychological profiles of children with common HM, such as neurofibromatosis type 1. Limited information is known regarding neuropsychological profiles of rare HM such as Osteochondromatosis Syndrome (OS) and Klippel-Trenaunay Syndrome (KTS). The current investigation is, to our knowledge, the first attempt to define the cognitive phenotypes in two boys with OS and KTS. Results revealed significantly greater impairments involving sensorimotor and visuospatial skills, while verbal memory and language skills appeared relatively preserved. Significant neurobehavioral problems and marked social difficulties were evident. These findings suggest that these syndromes are on a Nonverbal Learning Disorder (NLD) continuum, with varying degrees of severity.     

Alcohol-related amnesia and dementia: animal models have revealed the contributions of different etiological factors on neuropathology, neurochemical dysfunction and cognitive impairment

Chronic alcoholism is associated with impaired cognitive functioning. Over 75% of autopsied chronic alcoholics have significant brain damage and over 50% of detoxified alcoholics display some degree of learning and memory impairment. However, the relative contributions of different etiological factors to the development of alcohol-related neuropathology and cognitive impairment are questioned. One reason for this quandary is that both alcohol toxicity and thiamine deficiency result in brain damage and cognitive problems. Two alcohol-related neurological disorders, alcohol-associated dementia and Wernicke-Korsakoff syndrome have been modeled in rodents. These pre-clinical models have elucidated the relative contributions of ethanol toxicity and thiamine deficiency to the development of dementia and amnesia. What is observed in these models--from repeated and chronic ethanol exposure to thiamine deficiency--is a progression of both neural and cognitive dysregulation. Repeated binge exposure to ethanol leads to changes in neural plasticity by reducing GABAergic inhibition and facilitating glutamatergic excitation, long-term chronic ethanol exposure results in hippocampal and cortical cell loss as well as reduced hippocampal neurotrophin protein content critical for neural survival, and thiamine deficiency results in gross pathological lesions in the diencephalon, reduced neurotrophic protein levels, and neurotransmitters levels in the hippocampus and cortex. Behaviorally, after recovery from repeated or chronic ethanol exposure there is impairment in working or episodic memory that can recover with prolonged abstinence. In contrast, after thiamine deficiency there is severe and persistent spatial memory impairments and increased perseverative behavior. The interaction between ethanol and thiamine deficiency does not produce more behavioral or neural pathology, with the exception of reduction of white matter, than long-term thiamine deficiency alone.     

Memory impairment following ruptured aneurysm of the anterior communicating artery

This study reports the case of a 42-year-old man who suffered a ruptured aneurysm of the anterior communicating artery. His memory capabilities were assessed after a considerable recovery period during which many of his memory deficits ameliorated. His scan revealed a left frontal lesion and many of his deficits were characteristic of frontal impairment. He was impaired on temporal discrimination, and he showed marked source forgetting. He also performed badly on the Brown-Peterson task, and we suggest that this is another task that may be characteristic of frontal impairment. In contrast, the patient showed normal or near normal performance on some memory tasks but not on others. It is concluded that the patient's frontal signs are similar to those found in Korsakoff's Syndrome, but that his memory impairment is qualitatively different from that encountered in patients with the amnesic syndrome.     

Memory deficits among alcoholics: performance on a selective reminding task

This article compared alcoholics and healthy controls on the Buschke Selective Reminding Task. Alcoholics demonstrated deficits in memory and learning when compared to healthy controls, even when controlling for age. Examination of the alcoholic sample initially showed that age predicted memory deficits; however, age was no longer a significant predictor once the number of years of heavy drinking was entered into the regression equation. Findings suggest a direct link or mechanism of action between alcohol use and memory impairments, above and beyond effects of age or education.     

Memory for action events: findings in neurological patients

Encoding action phrases by enacting leads normally to better memory performance than verbal encoding. In order to gain additional insight into the representational basis of the enactment effect, neurological patients are contrasted with healthy participants. Persons suffering from Parkinson's disease, which primarily impairs the motor system, and patients suffering from Frontal Lobe Syndrome, which primarily affects action-related planning processes, were involved. We investigated whether the enactment effect would be differentially affected by these disorders. In addition, the characteristics of information processing after encoding by enacting was analyzed by varying memory material (unrelated versus clusterable actions) and by adding an encoding condition that included obligatory action planning (director condition). The findings indicate that the impact of motor information for the enactment effect is not dominant compared to the role of action-related cognitive and motivational processes, in particular planning processes. The findings of the two experiments are explained within traditional conceptual memory theories.     

Function and Dysfunction of Prefrontal Brain Circuitry in Alcoholic Korsakoff’s Syndrome

The signature symptom of alcohol-induced persisting amnestic disorder, more commonly referred to as alcoholic Korsakoff's syndrome (KS), is anterograde amnesia, or memory loss for recent events, and until the mid 20th Century, the putative brain damage was considered to be in diencephalic and medial temporal lobe structures. Overall intelligence, as measured by standardized IQ tests, usually remains intact. Preservation of IQ occurs because memories formed before the onset of prolonged heavy drinking--the types of information and abilities tapped by intelligence tests--remain relatively well preserved compared with memories recently acquired. However, clinical and experimental evidence has shown that neurobehavioral dysfunction in alcoholic patients with KS does include nonmnemonic abilities, and further brain damage involves extensive frontal and limbic circuitries. Among the abnormalities are confabulation, disruption of elements of executive functioning and cognitive control, and emotional impairments. Here, we discuss the relationship between neurobehavioral impairments in KS and alcoholism-related brain damage. More specifically, we examine the role of damage to prefrontal brain systems in the neuropsychological profile of alcoholic KS.     

Transgenic mice expressing a truncated form of CREB-binding protein (CBP) exhibit deficits in hippocampal synaptic plasticity and memory storage

Deletions, translocations, or point mutations in the CREB-binding protein (CBP) gene have been associated with Rubinstein-Taybi Syndrome; a human developmental disorder characterized by retarded growth and reduced mental function. To examine the role of CBP in memory, transgenic mice were generated in which the CaMKII alpha promoter drives expression of an inhibitory truncated CBP protein in forebrain neurons. Examination of hippocampal long-term potentiation (LTP), a form of synaptic plasticity thought to underlie memory storage, revealed significantly reduced late-phase LTP induced by dopamine-regulated potentiation in hippocampal slices from CBP transgenic mice. However, four-train induced late-phase LTP is normal. Behaviorally, CBP transgenic mice exhibited memory deficits in spatial learning in the Morris water maze and deficits in long-term memory for contextual fear conditioning, two hippocampus-dependent tasks. Together, these results demonstrate that CBP is involved in specific forms of hippocampal synaptic plasticity and hippocampus-dependent long-term memory formation.     

Memory Deficits Among Alcoholics: Performance on a Selective Reminding Task

ABSTRACT

This article compared alcoholics and healthy controls on the Buschke Selective Reminding Task. Alcoholics demonstrated deficits in memory and learning when compared to healthy controls, even when controlling for age. Examination of the alcoholic sample initially showed that age predicted memory deficits; however, age was no longer a significant predictor once the number of years of heavy drinking was entered into the regression equation. Findings suggest a direct link or mechanism of action between alcohol use and memory impairments, above and beyond effects of age or education.     

Translational Rodent Models of Korsakoff Syndrome Reveal the Critical Neuroanatomical Substrates of Memory Dysfunction and Recovery

Investigation of the amnesic disorder Korsakoff Syndrome (KS) has been vital in elucidating the critical brain regions involved in learning and memory. Although the thalamus and mammillary bodies are the primary sites of neuropathology in KS, functional deactivation of the hippocampus and certain cortical regions also contributes to the chronic cognitive dysfunction reported in KS. The rodent pyrithiamine-induced thiamine deficiency (PTD) model has been used to study the extent of hippocampal and cortical neuroadaptations in KS. In the PTD model, the hippocampus, frontal and retrosplenial cortical regions display loss of cholinergic innervation, decreases in behaviorally stimulated acetylcholine release and reductions in neurotrophins. While PTD treatment results in significant impairment in measures of spatial learning and memory, other cognitive processes are left intact and may be recruited to improve cognitive outcome. In addition, behavioral recovery can be stimulated in the PTD model by increasing acetylcholine levels in the medial septum, hippocampus and frontal cortex, but not in the retrosplenial cortex. These data indicate that although the hippocampus and frontal cortex are involved in the pathogenesis of KS, these regions retain neuroplasticity and may be critical targets for improving cognitive outcome in KS.     

Neuropsychological characteristics of children with the 22q11 Deletion Syndrome: a descriptive analysis.

Previous reports of cognitive functioning in children with the 22q11 Deletion Syndrome have reported marked variability in IQ and achievement subtest scores. Studies have begun to explore neuropsychological function in 22q11 DS however results are inconsistent and the profile incomplete. We assessed 40 children ages 5-12 with 22q11 DS. Consistent with past results, visual-spatial memory was significantly lower than verbal memory. Differentially lowered scores were found only in visual attention, working memory and motor function. Contrary with some past results quantitative, verbal ability, and visual spatial memory scores were within 1 SD from the standardization sample mean. Motor behavior, not typically discussed with regard to 22q11 DS school-age children, may be critical to incorporate in neurocognitive studies of children with 22q11 DS. Implications of these findings are considered with regard to past results.     

Women, “False” Memory,and Personal Identity

We contest each other's memory claims all the time. I am concerned with how the contesting of memory claims and narratives may be an integral part of many abusive situations. I use the writings of Otto Weininger and the False Memory Syndrome Foundation to explore a particular strategy of discrediting women as rememberers, making them more vulnerable to sexual harm. This strategy relies on the presentation of women as unable to maintain a stable enough sense of self or identity to be trustworthy testifiers to their own harm.     

Memory and Affect: Autobiographical Memory Distribution and Availability in Normal Adults and Recently Detoxifed Alcoholics

An autobiographical memory task was administered to a group of 15 male alcoholics (duration of abuse x = 16 years) and to a control group comprised of 15 nonabusers. The alcoholics were inpatients in a chemical dependence treatment program who had their last drink 8 days prior to testing. Two aspects of autobiographical memory were compared. First, the distribution of memories for life events over the lifespan clearly differed for the two groups. The alcoholic group recalled far fewer memories from the most recent 5 years and showed an exaggerated tendency to recall memories from their early adulthood when compared to the control group. This result is consistent with a model of the onset of a temporally graded retrograde amnesia subsequent to a protracted period of alcohol abuse. In such cases the context for self-evaluation may remain heavily rooted in late adolescence. Second, in contrast to results of the control group, the data from men in the alcohol group revealed no relationship between latency to report autobiographical memories associated with a particular affect and self-rated frequency of such affects. This dissociation indicates the possible impact of atypical memory performance on views of the self.