Alcoholic Korsakoff Research Articles

Cerebral Vascular Transit Time in Alzheimer's Disease and Korsakoff's Psychosis and its Relation to Cognitive Function

The cerebral vascular transit time of 17 patients with pre-senile dementia of the Alzheimer type (ATD), nine abstinent patients with alcoholic Korsakoff's psychosis (KOR), and ten age-matched controls was determined by the bolus intravenous injection of pertechnetate. A gamma camera was used to estimate the median transit time (MTT) of the radioactive bolus in a planar (non-tomographic) projection normal to the vertex. The spread of the bolus arriving at the aortic arch was measured independently by a single external detector over the chest, and correction made for the transit time of this input function in calculating the net MTT for the head. Both ATD and KOR groups showed lengthened net MTTs, compatible with reduced cerebral blood flow, and which were correlated with reduced cognitive function. It is concluded that the method employed gives a simple, inexpensive estimate of function-related blood flow to the brain in pre-senile dementia.

The neurology of memory: quantitative assessment of retrograde amnesia in two groups of amnesic patients

The phenomenon of retrograde amnesia has important implications for understanding normal memory as well as its neural organization. Using 6 tests of remote memory, we evaluated the extent and severity of retrograde amnesia in 2 groups of amnesic patients--7 patients with alcoholic Korsakoff's syndrome and 5 other patients with amnesia (anoxia or ischemia, N = 3; thalamic infarction, N = 1; unknown etiology, N = 1). Although there were individual differences, Experiment 1 showed that the severity and extent of retrograde amnesia was similar for the 2 groups. Retrograde amnesia was temporally graded across a period of about 15 years and was not detectable in more remote time periods. In Experiment 2, repeated testing during a 3 year period showed that amnesic patients and control subjects were similarly consistent in their responses. Amnesic patients did not catch up to control subjects by eventually accumulating as many correct answers as the control subjects. In Experiment 3, amnesic patients performed normally on a test of very difficult general information questions, which were based on material likely to have been learned long ago. In all 3 experiments, the 2 groups of amnesic patients performed similarly. The results support the following conclusions: (1) Extensive, temporally graded retrograde amnesia, which has been observed frequently in patients with Korsakoff's syndrome, occurs readily in other amnesic patients as well, even when their memory impairment appears well circumscribed; (2) patients with presumed damage to either the medial temporal or the diencephalic brain structures linked to memory functions can produce a similar kind of retrograde amnesia; (3) the impairment reflects a loss of usable knowledge, not simply difficulty accessing an intact memory store that can then be overcome given sufficient retrieval opportunities; (4) very remote memory, at least for factual information, can be intact in amnesia; (5) the structures damaged in amnesia support memory storage, retrieval, or both during a lengthy period of reorganization, after which representations in memory can become independent of these structures.

Attempted clinical application of a technique for promoting robust free recall to a case of alcoholic Korsakoff's syndrome

A case study is reported which attempted to teach personal orienting information (i.e., recent history) to an amnesic male patient. The structured cuing methods reported by Kovner, Mattis, and Pass (1985, Journal of Clinical and Experimental Neuropsychology, 7, 395–411) were adopted. This involves structured presentation and cuing of target words embedded in a narrative. Some patients eventually are able to freely recall large amounts of material presented in this way. In the present case, the patient received 30 training sessions over 8 weeks. The material to be remembered was 10 target words pertaining to recent personal history. These words were embedded in accompanying storyline. The patient's immediate recall at the end of each session improved to some extent over the training period. However, delayed recall for the material remained nil throughout. Twelve months after the last training session the patient showed some “implicit” retention of the material. The findings are contrasted with Kovner et al.'s dramatic results and discussed.

Alcoholism, Korsakoff’s Syndrome and the Frontal Lobes

A subset of the diffuse cerebral changes and psychometric deficits found in chronic alcoholics is similar to that seen in the frontal lobe syndrome. Certain features of alcoholic Korsakoff's syndrome (AKS) also point to cortical involvement, and this may have a basis in alcohol neurotoxicity. Twenty-five patients with AKS and 24 non-Korsakoff alcoholic controls were compared using an automated CT brain scan program. In addition to evidence of their diencephalic lesions (wide third ventricles), AKS patients revealed widespread cerebral damage with greater Sylvian and interhemispheric fissure (IHF) size than alcoholics. Korsakoffs were also inferior to alcoholics in performance on a category sorting test, in which non-perseverative error scores correlated significantly with IHF size. The principle of distinguishing between selective memory decline and global intellectual decline (GID) was applied to 38 patients with AKS. Indices were developed for each type of deficit and much variation found in their distributions. The degree of GID correlated significantly with IHF size, showing similar trends with other cortical measures. These results suggest a cortical substrate for the degree of GID and a frontal substrate for category sorting deficits; with a probable basis in alcohol neurotoxicity rather than thiamine deficiency, which is not known to impair cortical structure. A new model is proposed of the pathophysiology of alcoholic brain damage and AKS which includes recent work on neurotransmitter sources and thalamo-frontal connections.

Alcoholism, Korsakoff's Syndrome and the Frontal Lobes.

A subset of the diffuse cerebral changes and psychometric deficits found in chronic alcoholics is similar to that seen in the frontal lobe syndrome. Certain features of alcoholic Korsakoff's syndrome (AKS) also point to cortical involvement, and this may have a basis in alcohol neurotoxicity.Twenty-five patients with AKS and 24 non-Korsakoff alcoholic controls were compared using an automated CT brain scan program. In addition to evidence of their diencephalic lesions (wide third ventricles), AKS patients revealed widespread cerebral damage with greater Sylvian and interhemispheric fissure (IHF) size than alcoholics. Korsakoffs were also inferior to alcoholics in performance on a category sorting test, in which non-perseverative error scores correlated significantly with IHF size.The principle of distinguishing between selective memory decline and global intellectual decline (GID) was applied to 38 patients with AKS. Indices were developed for each type of deficit and much variation found in their distributions. The degree of GID correlated significantly with IHF size, showing similar trends with other cortical measures.These results suggest a cortical substrate for the degree of GID and a frontal substrate for category sorting deficits; with a probable basis in alcohol neurotoxicity rather than thiamine deficiency, which is not known to impair cortical structure. A new model is proposed of the pathophysiology of alcoholic brain damage and AKS which includes recent work on neurotransmitter sources and thalamo-frontal connections.

Memory strategies with brain damage

The ability of anterograde amnesics with and without a history of alcoholism and patients with frontal lobe damage to think about memory, memorizing, and remembering was assessed. Alcoholic Korsakoffs' and frontal lobe patients' knowledge and use of memory strategies was deficient when compared with controls whereas nonalcoholic amnesics' was not. The use of the categorization mnemonic was assessed in a verbal learning experiment. Frontal lobe patients failed to spontaneously categorize a categorizable word list when trying to memorize it. Nevertheless, when forced to categorize the list, they benefited from the imposed structure. Nonalcoholic amnesics spontaneously categorized the list and benefited from the resulting organization.

Effects of Instructional Set on Amnesic Recognition Memory Performance

Tests that tapped memory for spatial location, temporal order, frequency of occurrence, category membership were administered to a group of alcoholic Korsakoff patients, a group of mixed amnesic patients with primarily temporal lobe pathology, a group of normal subjects. The four tests were administered with incidental as well as intentional learning conditions. All groups performed better in the intentional than the incidental condition of the category recognition test. None of the groups performed better in the intentional than the incidental conditions on any of the other tests. The data were interpreted as implying that amnesic patients do not benefit from intentional learning conditions in tests of memory for contextual stimuli.

Lexical and semantic priming deficits in patients with Alzheimer's disease.

Two experiments utilizing priming procedures examined the status of semantic memory in demented and amnesic patients. In the first investigation, lexical priming was assessed in patients with dementia of the Alzheimer type (DAT), Huntington's Disease (HD), alcoholic Korsakoff's syndrome (KS), and in intact control subjects. Subjects were first exposed to a list of words in a rating task and then required to complete three-letter stems with the "first word that comes to mind". Half of the stems could be completed with the previously presented words and the other half were used to assess baseline guessing rates. Recall and recognition of incidentally exposed words was also assessed. Although all three patient groups were impaired on tests of recall and recognition, only the DAT patients exhibited a priming deficit on the stem-completion task. In the second experiment, DAT, HD, and intact control subjects were administered a semantic priming test which required the subject to "free associate" to the first words of previously presented semantically associated word pairs. The results for this association task showed that DAT patients were significantly less likely to produce the second word of the semantically related pair than were the other subject groups. The results of these two experiments suggest that the memory capacities of DAT patients are characterized by a breakdown in the structure of semantic memory and that this impairment is evident on some "automatic" as well as "effortful" processing tasks.

Associative encoding and retrieval in Alzheimer's and Huntington's disease

The associative encoding and retrieval abilities of patients with dementia of the Alzheimer type (DAT) and patients with Huntington's disease (HD) were investigated using an encoding specificity paradigm. When compared to age- and education-matched intact control subjects, both patient groups were severely (and equally) impaired on overall memory for word lists. However, the HD and DAT patients showed differential improvement in recall performance with the introduction of associated cues during stimulus presentation and recall. Although the HD patients, like intact subjects, were able to benefit from semantic retrieval cues (strong and weak) which were present during input, the performance of the patients with DAT improved only with the introduction of strong cues at output, regardless of whether the cues were present or absent during initial presentation. These findings suggest that patients with DAT failed to encode the semantic relationship between the to-be-recalled and cue words and simply generated free associations to the cue words during retrieval. Similarities between the performances of the patients with DAT and alcoholic Korsakoff patients are noted and discussed with regard to the neuropathological basis of the disorders.

Deficits in the implicit retention of new associations by alcoholic Korsakoff patients

Word-stem completion in the presence or absence of a paired associate was assessed for a group of amnesic Korsakoff patients and a group of alcoholic controls. Since neither group demonstrated facilitation in the presence of cues (Experiment 1), an analysis of the influence of instructions to remember the paired associates on cued word-stem completion was performed with college students (Experiment 2). Finding a positive effect of instructions led to a replication of the task with amnesic patients and alcoholic controls. Unfortunately, instructions to remember the pairs did not produce the facilitatory effect for either group nor for an age matched nonalcoholic control group. (Experiment 3). It was concluded that neither amnesics, chronic alcoholics, nor elderly controls had the ability to modify their analysis of verbal material as a function of retrieval expectations. As a consequence, neither group demonstrated the effect of contextual priming of word completions reported by P. Graf and D. L. Schacter (1985, Journal of Experimental Psychology: Learning, Memory and Cognition, 11, 501–518).

The implicit memory ability of a patient with amnesia due to encephalitis

The implicit memory ability of a patient (S.S.) with severe amnesia due to encephalitis was assessed using five independent paradigms: Perceptual priming with real words and pseudowords; Word-stem completion with and without contextual cues; Word-stem completion following presentation of high- vs. low-frequency words; Biasing of the spelling of ambiguous (homophonic) words; and Conceptual priming. On the tasks in which previously acquired knowledge could potentially be activated by a prime (e.g., perceptual priming with real words), both S.S. and the Korsakoff patients performed on a normal level. However, when new learning or new associations had to be formed prior to implicit memory testing (e.g., perceptual priming of pseudowords or contextual word-stem completion), S.S.'s implicit memory performance was superior to Korsakoff amnesics. These results suggested that new learning differentially affects the priming abilities of S.S. and alcoholic Korsakoff patients. Since S.S.'s amnesia is as severe as Korsakoff patients, it was also concluded that severity of amnesia is clearly not the sole determinant of priming capacity; etiology may be equally important.

Thalamic Amnesia: Clinical and Experimental Aspects

One of the most interesting and important aspects of human behavior involves learning and memory. There is no question that clinical disorders of memory not only provide syndromes that are of significant theoretical interest, but also constitute, in some patients, a source of marked disability. The alcoholic Korsakoff syndrome, for example, constitutes a clinical problem of significant magnitude. In this regard, information about the neural basis for memory, derived from clinical or experimental observations, is of considerable importance. It is the purpose of this chapter to summarize the available evidence concerning one particular type of memory disorder that has a discrete neuro-anatomical substrate—that is, thalamic amnesia. Recognition of this syndrome is of obvious clinical importance because it can occur as a result of disorders—for example, neoplasm, infarction, hemorrhage—that require prompt and accurate diagnosis and treatment. This disorder also, however, has theoretical importance in pointing toward some of the central nervous system (CNS) structures that are required for intact memory function in mammals. Previous studies on the effects of focal lesions on memory have suggested the involvement of a number of structures. These include the hippocampus, temporal lobe, temporal stem, fornix, and cerebellar nuclei. There is evidence implicating each of these areas in memory function within the mammalian brain. This chapter discusses another nuclear area, the mediodorsal thalamus, which may play a role in memory and describes the amnestic deficits that may occur as a result of relatively discrete lesions of this diencephalic region.

Measuring the course of Alzheimer's disease. A longitudinal study of neuropsychological function and changes in P3 event-related potential.

On two occasions one year apart, the cognitive performance of 12 patients with presenile dementia Alzheimer type (ATD) and 14 with alcoholic Korsakoff syndrome (KS) was assessed both psychologically using the Christensen version of Luria's neuropsychological investigation and physiologically by measuring P300 (P3) and other long-latency auditory event-related potentials. All patients with ATD showed evidence of psychological deterioration and most also showed changes in auditory P3, whereas on all measures the KS group remained essentially unchanged. The extent of the changes in the ATD group varied, but in general those patients with most psychological deterioration also displayed the biggest changes in P3 wave form. There were two patterns of decline: a majority followed the traditional progressive course associated with Alzheimer disease; and in a minority, decline was slower. Methods for determining the rate of decline in individual patients with ATD, together with the prognostic implications, are discussed.

Lexical Acquisition in Alcoholic Korsakoff Psychosis

Recent studies have underlined the importance of the distinction between “declarative” and “procedural” aspects of memory functioning. The purpose of the present study is to evaluate the relative deficits in these two aspects of anterograde memory in an amnesic population with midline diencephalic lesions, to determine whether this apparently fundamental distinction in memory types is honored even under real-world conditions. Eight alcoholic Korsakoff patients were examined for their lexical acquisition capacity, including both their application of word-learning procedures to a new lexical domain and their eventual recall of the facts represented by the new word. The findings revealed that each Korsakoff patient successfully applies at least some of the procedures subserving the word-learning process to the new lexical domain. By comparison, the Korsakoff patients subsequently acquire little of the factual knowledge represented by the new word. Specifically, almost all of the patients recognize only the object used during the exposure period to demonstrate the new word. Quantitative and qualitative features of the patients' declarative and procedural memory deficits are discusses in the context of real-world processing advantages and limitations.

Selective memory loss and global intellectual deficits in alcoholic Korsakoff's syndrome.

The principle of distinguishing between selective memory deterioration and global intellectual decline has been applied to 38 patients with alcoholic Korsakoff's syndrome. Indices were developed for each type of deficit and their distributions explored. Considerable variation was seen in both parameters, the transition from pure memory loss to global intellectual deficits appearing to be gradual. Differences were found in the sex and CT scan associations of the indices. The implications of the distinction for future research are discussed.

Memory dysfunction and word priming in dementia and amnesia.

Memory performance of patients with the clinical diagnosis of Alzheimer's disease was compared with performance of patients with alcoholic Korsakoff's syndrome and patients with Huntington's disease. Although all patient groups exhibited impairment on tests of verbal memory, only patients with Alzheimer's disease exhibited impaired priming. Priming is an unconscious expression of recently encountered material, and it is intact even in severely amnesic patients. Because mildly demented patients with Alzheimer's disease exhibited impaired priming, damage to brain structures in addition to those damaged in the amnesic syndrome must occur at a relatively early stage of the disease process.

On localization versus systemic effects in alcoholic Korsakoff's syndrome: a comment on Butters (1985).

In a recent article, Butters (1985) emphasized that involvement of the nucleus basalis of Meynert may be the critical area affected in alcoholic Korsakoff's syndrome. Examination of the neuroanatomical pathways between this structure and other neural structures involved in memory (i.e., hippocampus and dorsal medial thalamus) suggests a somewhat different emphasis might be more productive in facilitating understanding of memory processes. The important question is: In what way might the nucleus basalis of Meynert interact with other structures involved in memory processes? Other data also suggest that it will be necessary to emphasize a whole system of brain structures as opposed to one or two small nuclei.

Biasing of alcoholic Korsakoff patients' semantic memory.

The extent to which the spelling of ambiguous words could be biased and the length of time this biasing could be maintained were investigated in three studies. Biasing occurred for amnesic Korsakoff patients but the effect was consistently more fragile than the biasing pattern of alcoholic control patients. Between-group differences were due to the differential dependency of amnesics' biasing upon the activation of semantic memory. The spelling bias of the alcoholic control patients appeared to be based on both semantic activation and episodic retention.

Some analyses of forgetting of pictorial material in amnesic and demented patients.

Three experiments evaluating the rate of forgetting of pictorial stimuli in amnesic, demented, and normal control subjects are reported. When prolonged exposures of pictorial material were used to equate recognition performance after a 10-min delay, alcoholic Korsakoff (AK) patients and patients with Huntington's Disease (HD) demonstrated normal rates of forgetting over a 1-week period. In addition to replicating previous findings with AK patients, these results are consistent with recent suggestions that retrieval, not storage, deficiencies characterize the HD patients' memory problems. The second experiment explored whether the AK and HD patients learned as much about the features of the pictorial stimuli as did the normal subjects. After the subjects viewed a series of pictorial stimuli, recognition was assessed 10 min later using the whole pictures, isolated main features of the pictures, or isolated peripheral features of the pictures. The results showed that, with prolonged exposure times, the two patient groups did not differ from the normal control group in terms of the features of the stimuli they analyzed and remembered. The third experiment evaluated the rate of forgetting of pictorial material of two groups ("young" and "old") of normal subjects, one group ("old") having viewed each picture for 1 s and the other group ("young") for .5 s. Although the two groups did not differ in recognition performance 10 min after presentation, the young subjects who viewed each picture for .5 s showed more rapid forgetting over a 1-week period. This finding indicates that similar recognition scores do not necessarily signify equal learning under all exposure conditions.

A monoclonal antibody assay technique for plasma and red cell acetylcholinesterase activity in Alzheimer's disease

Acetylcholinesterases (AChE) in human plasma and red cells have been considered as possible markers for Alzheimer's disease. Findings however vary widely and no significant pattern has emerged. The present study has used a new technique for AChE assay based on a monoclonal antibody raised against red cell AChE. This allows AChE isoenzymes to be measured directly in the presence of non-specific cholinesterases without the need for inhibitors. AChE activity in plasma and red cells was assayed in Alzheimer's disease, multi-infarct dementia, Huntington's and alcoholic Korsakoff syndrome, and the results compared both between groups and with normal controls. No significant differences in either red cell or plasma enzyme activity were found by any of these comparisons. Our findings do not suggest that in the dementias peripheral AChE activity reflects altered central cholinergic function, nor that it is likely to prove a useful marker for Alzheimer's disease.