Michael Kopelman

Rates of forgetting in Alzheimer-type dementia and Korsakoff's syndrome

After initial learning had been equated as closely as possible, 16 Alzheimer-type dementing patients showed the same rate of forgetting on a picture recognition test administered at intervals over the course of a week as 16 Korsakoff patients and 16 healthy controls. This suggested that the anterograde amnesic deficit in both Alzheimers disease and Korsakoffs syndrome is primarily an acquisition or learning deficit. The Alzheimer patients differed from both the Korsakoff patients and the healthy controls in showing diminished digit span and severely impaired performance at the Brown-Peterson test, implicating a deficit of short-term (or working) memory. The variability of performance within groups on the principal tests employed was also examined; and the Alzheimer results are discussed with respect to the underlying neuropathology, and the implication for pharmacotherapy.

Two types of confabulation.

Examples of confabulation in Korsakoff patients, Alzheimer-type dementing patients, and healthy subjects are discussed. It is argued that there may be two types of confabulation: spontaneous confabulation, which may result from the superimposition of frontal dysfunction on an organic amnesia, and provoked confabulation, which may reflect a normal response to a faulty memory. In the present study, instances of provoked confabulation, given by Korsakoff and Alzheimer patients in story recall, were compared with those produced by healthy subjects at a prolonged retention interval.

The National Adult Reading Test as a measure of premorbid intelligence: A comparison with estimates derived from demographic variables

Since its publication in 1982, the National Adult Reading Test (NART; Revised Version, NART-R) has become a widely accepted method for estimating premorbid levels of intelligence in neuropsychological research. However, the assumption that NART/NART-R performance is relatively independent of brain damage has been increasingly challenged in recent years. In a number of conditions, including Alzheimer dementia and Korsakoffs syndrome, studies have indicated a deterioration in reading ability, leading to an underestimated premorbid IQ. In a reaction to these studies, some researchers have advocated the use of demographic variables as a more suitable foundation for accurately predicting premorbid intelligence. We addressed this issue by calculating IQ estimates on the basis of NART/NART-R, demographic variables, and a combination of the two approaches and by comparing these with current WAIS/WAIS-R IQ in patients with Korsakoffs syndrome, Alzheimer dementia, frontal or temporal lobe lesions, and in healthy controls. Estimated premorbid IQs did not differ across groups, whether derived from NART/NART-R or demographic variables. Those based on NART/NART-R demonstrated higher correlations with current WAIS/WAIS-R IQ in controls and patients than those derived from demographic variables. An equation combining NART scores with demographic variables did not significantly increase the amount of variance in IQ explained by NART only, either in patients or controls. The data offer reassurance regarding the continued use of NART as a valid estimate of premorbid intelligence in a number of conditions.

The Memory Deficits in Alzheimer-Type Dementia: A Review:

This review is an account of recent experimental studies of memory deficits at the early stages of Alzheimer-type dementia, evaluating these studies in relation to current theories of memory functioning in humans. Whilst memory deficits are found to be widespread, some aspects are more resilient to impairment than others. For example, the processes associated with articulatory rehearsal in working memory are unimpaired despite a reduction in performance on most tests of primary memory. The “implicit” aspects of secondary memory appear to remain unimpaired, in contrast to a marked decline in “explicit” or “episodic” memory. In addition, there is evidence that the rate of forgetting from secondary memory is normal. Some aspects of episodic and semantic memory are found to be impaired as a consequence of a decline in the efficient organisation and processing of verbal material at encoding or retrieval. It is concluded that the deficits share particular features found in organic amnesia, but with additional deficits which relate to impairments in other domains of functioning.

The Cholinergic Neurotransmitter System in Human Memory and Dementia: A Review:

The present paper reviews three types of evidence implicating the role of acetylcholine in human memory and dementia: (1) neuropathological evidence that the cholinergic transmitter system is depleted in Alzheimer-type dementia; (2) psychopharmacological studies that have employed “cholinergic blockade” as a model of cholinergic depletion; and (3) clinical studies of cholinergic “replacement” therapy in Alzheimer-type dementia. The evidence that the cholinergic system is depleted in Alzheimer-type dementia has been complemented by the finding that cholinergic blockade in healthy subjects causes a substantial learning (or “acquisition”) deficit in episodic memory. The overall results of studies of replacement therapy have generally been disappointing, but a few have reported benefits in recall and recognition tests. The role of the cholinergic system in many aspects of memory remains to be elucidated; but it seems unlikely that cholinergic depletion accounts for all aspects of the memory disorder in Alzheimer-type dementia, and possibly the depletions of other neurotransmitters also contribute to the memory impairment.

Spared numerical abilities in a case of semantic dementia

We report a case study of a patient (IH) with a progressive impairment of semantic memory affecting all categories of knowledge apart from numbers. Pictorial material was better understood than words, but was still severely impaired. The selective preservation of nearly all aspects of numerical knowledge suggested that this domain might have different neuropsychological status from other aspects of semantic memory.

Temporal and spatial context memory in patients with focal frontal, temporal lobe, and diencephalic lesions.

Patients with focal frontal, temporal lobe, or diencephalic lesions were investigated on measures of temporal (recency) and spatial (position) context memory, after manipulating exposure times to match recognition memory for targets (pictorial stimuli) as closely as possible. Patients with diencephalic lesions from an alcoholic Korsakoff syndrome showed significant impairment on the temporal context (recency) task, as did patients with frontal lesions penetrating the dorsolateral frontal cortex, according to MRI (and PET) evidence. Patients with temporal lobe lesions showed only a moderate (non-significant) impairment on this task, and patients with medial frontal lesions, or large frontal lesions not penetrating the dorsolateral cortical margins, performed as well as healthy controls at this task. On the spatial context memory task, patients with lesions in the temporal lobes showed significant impairment, and patients with right temporal lesions performed significantly worse than patients with left temporal lesions. Patients with diencephalic lesions showed only a modest (non-significant) impairment on this task, and the frontal lobe group performed normally. When a group of patients with temporal lobe lesions resulting from herpes encephalitis were examined separately, an identical pattern of results was obtained, the herpes group being significantly impaired on spatial memory and showing a trend towards impairment for temporal context memory. There were strong correlations between anterograde memory quotients and context memory performance (despite the use of an exposure time titration procedure) and a weak association in the frontal group with one frontal/executive task [corrected] (card-sorting perservations). It is predicted that correlations between temporal context memory and frontal/executive tasks will be greater in samples of patients all of whom have frontal lesions invading the dorsolateral cortical margin.

Focal retrograde amnesia and the attribution of causality: An exceptionally critical view

A detailed critique of the literature on focal retrograde amnesia is provided. Some of the cases commonly cited in this literature had, in fact, severely impaired anterograde memory, most often involving visuospatial material. Other cases showed poor anterograde memory in more moderate or subtle form, begging the question of whether “like” had really been compared with “like” across the retrograde and anterograde domains: there may be alternative explanations for the observed patterns of performance. One suggestion is that these patients suffer an impairment of long-term consolidation, an attractive hypothesis but one which requires much more rigorous testing than has occurred to date and which implies that the underlying problem is not specific to retrograde memory. Moreover, within the literature on cases of focal retrograde amnesia, differing patterns of performance on tests of autobiographical memory or remote semantic knowledge have been reported, and sometimes these may have reflected factors other than the sites of lesions. Many of the most convincing cases in this literature have been those in whom there was an initially severe anterograde amnesia as well as an extensive retrograde loss: in these cases, the critical issue is what determines differential patterns of recovery across these domains-it is likely that both physiological and psychological factors are important. A second, somewhat different, group are patients with semantic dementia, who show a pronounced recency effect in remote memory but, in these cases, the most parsimonious explanation may be in terms of predominantly semantic/linguistic and/or strategic factors. A third group are those with transient epileptic amnesia but, in these cases, the memory gaps may reflect past (anterograde) ictal activity. A fourth group are those in whom psychogenic factors may well be relevant. Although it is difficult to “prove” psychological causation, the logical difficulties in attributing causation where brain lesions are either very subtle or multiple have been considerably underestimated in the neuropsychological literature. Given these problems, in uncertain or equivocal cases, it is as critical to present the relevant psychological data for the reader to evaluate as it is to provide the pertinent memory test scores: this is underemphasised in many of the studies reviewed. Publication of cases in the absence of such data may lead to faulty clinical, neuropsychological, and cognitive conclusions. Abbreviations : AA: anterograde amnesia; AMI: Autobiographical Memory Interview; PTA: posttraumatic amnesia; RA: retrograde amnesia; RMT: Recognition Memory Test; TEA: transient epileptic amnesia; TGA: transient global amnesia; WMS: Wechsler Memory Scale.

FDG-PET findings in the Wernicke-Korsakoff syndrome.

This study reports FDG-PET findings in Wernicke-Korsakoff patients. Twelve patients suffering amnesia arising from the Korsakoff syndrome were compared with 10 control subjects without alcohol-related disability. Subjects received [18F]-fluorodeoxyglucose (FDG-PET) imaging as well as neuropsychological assessment and high-resolution MR imaging with volumetric analysis. Volumetric MRI analysis had revealed thalamic and mamillary body atrophy in the patient group as well as frontal lobe atrophy with relative sparing of medial temporal lobe structures. Differences in regional metabolism were identified using complementary region of interest (ROI) and statistical parametric mapping (SPM) approaches employing either absolute methods or a reference region approach to increase statistical power. In general, we found relative hypermetabolism in white matter and hypometabolism in subcortical grey matter in Korsakoff patients. When FDG uptake ratios were examined with occipital lobe metabolism as covariate reference region, Korsakoff patients showed widespread bilateral white matter hypermetabolism on both SPM and ROI analysis. When white matter metabolism was the reference covariate; Korsakoff patients showed relative hypometabolism in the diencephalic grey matter, consistent with their known underlying neuropathology, and medial temporal and retrosplenial hypometabolism, interpreted as secondary metabolic effects within the diencephalic-limbic memory circuits. There was also evidence of a variable degree of more general frontotemporal neocortical hypometabolism on some, but not all, analyses.

The role of motor intention in motor awareness: an experimental study on anosognosia for hemiplegia

Recent theories propose that anosognosia for hemiplegia (AHP) results from specific impairments in motor planning. However, no study has hitherto directly investigated the role of motor intention in the observed non-veridical awareness of action in AHP. We developed the following paradigm to investigate the role of motor planning in awareness in patients with AHP: Four hemiplegic patients with and four without anosognosia were provided with false visual feedback of movement in their left paralysed arm through a prosthetic rubber hand. We examined whether the ability to detect presence or absence of movement based on visual evidence varied according to whether the patient had planned to move their limb or not. Motor intention had a selective effect on patients with AHP; they were more likely than controls (U = 16, P < 0.001) to ignore the visual feedback of a motionless hand and claim that they moved it when they had the intention to do so (self-generated movement) than when they expected an experimenter to move their own hand (externally generated movement), or there was no expectation of movement. By contrast, patients without AHP were not influenced by these manipulations, and did not claim they moved their hand when the hand remained still. This is the first direct demonstration that altered awareness of action in AHP reflects a dominance of motor intention prior to action over sensory information about the actual effects of movement.