Abstract

We report the neuropsychological profile associated with variant Creutzfeldt–Jakob disease (vCJD). A retrospective study was carried out of data from neuropsychological reports prepared on 24 patients with vCJD. While there was some variability in neuropsychological profiles, the overall pattern was one of a combined cortical and subcortical dementia, with impaired performance being particularly prominent on tests of memory, executive function, speed of attention, and visuoperceptual reasoning. Across 16 cases where Wechsler Adult Intelligence Scale‐Revised intelligence quotient (IQ) scores were available, this profile was in part reflected by an invariably low performance IQ (<90 in all patients). All patients who received tests of verbal fluency, digit‐symbol substitution and faces recognition memory showed deficits on these tests. Basic vocabulary, digit span and verbal reasoning skills were relatively preserved in most patients. In four cases who underwent more detailed cognitive testing, additional observations were made of relatively intact long‐term autobiographical memory and faces perception. Cognitive impairment may represent one of the earliest features of vCJD and it is possible that, at least in some cases, neuropsychological deficits precede the onset of psychiatric or neurological symptoms. Our findings may help in the early detection and management of patients with vCJD.

Introduction

Variant Creutzfeldt–Jakob disease (vCJD) is a distinctive and unusual form of prion disease (Will et al., 1996; Prusiner, 2001). Clinical studies of sporadic and genetic forms of Creutzfeldt–Jakob disease (CJD) have noted cognitive difficulties (Brown et al., 1984; Birmingham and Brett, 1999), while more detailed single‐case studies have pointed to focal disturbances in language (e.g. Mandell et al., 1989; Kirk and Ang, 1994), vision (e.g. Vargas et al., 1995; McElvanney and Boodhoo, 1999; Jacobs et al., 2001; Pachalska et al., 2001), hearing (Tobias et al., 1994; Cataldi et al., 2000; Orimo et al., 2000) and executive function (Zarei et al., 2002). However, there is little evidence relating to the neuropsychological profile associated with vCJD. In one recent single‐case study, Kapur et al. (2001) found evidence for memory and executive dysfunction in a case of pathologically verified vCJD.

While there has been a major emphasis on the psychiatric features associated with vCJD (Zeidler et al., 1997), with impaired memory and concentration having been reported to follow rather than precede changes in mood, temperament and behaviour (Spencer et al., 2002), it remains possible that early cognitive difficulties may lead to symptoms of frustration, anxiety and depression and that, with appropriate test procedures, neuropsychological deficits in the early stages of the disease may be detected. The purpose of this article is to report a retrospective analysis of evidence from neuropsychological reports relating to 24 patients with a probable (n = 4) or pathologically verified (n = 20), diagnosis of vCJD.

Methods

All the cases of probable or pathologically verified vCJD that had been documented by the UK’s National CJD Surveillance Unit by 31st March 2002 were considered for inclusion in the study (n = 117). Information held at the Unit was reviewed for information on neuropsychological testing, either from copies of the hospital notes or copies of hospital letters. Thirty‐four cases were identified in which neuropsychological testing had been carried out and in which there was sufficiently detailed information on test findings to enable a retrospective analysis to be conducted. In each case, permission was sought from the relevant psychologist to use the data on neuropsychological testing in this paper. From a consideration of the relevant clinical material, there was no evidence that the cases with neuropsychological reports differed in any significant ways from those where neuropsychological testing had not been carried out, or in cases where minimal neuropsychological findings were reported. Thus, the mode of onset was psychiatric in 50% of the cases reported in this paper compared with 63% for the first 100 cases of vCJD. In addition, 25% had a neurological onset compared with 15% in the first 100 cases. In the remaining 25% cases in our sample, the onset was mixed.

We recorded the test results that were reported for each case. In a number of cases, additional information and clarification were provided by the neuropsychologist who had prepared the original reports. Of the 117 cases, there were 34 cases where we could establish that neuropsychological testing had been carried out, and where there was sufficient detailed information on test findings to enable a retrospective analysis to be conducted and where permission to use the data was sought. We recorded the test results that were reported for each case.

Results

Of the 34 cases with available neuropsychological test reports, permission to include the results in this paper was obtained in 24 cases and the results from this cohort of patients are the basis of our analyses. The mean age of the 24 cases was 29 years at death and the mean duration of illness was 13 months, consistent with these parameters in the overall cohort of patients with vCJD.

The timing of neuropsychological testing in each case is shown in Fig. 1. The mean time from onset of clinical symptoms to the timing of neuropsychological assessment was 8 months (range 2–16 months) and the mean delay from neuropsychological testing to death was 5 months (range 3–12 months). The overall proportion of illness that had elapsed by the time neuropsychological testing was undertaken was 59% (33–79%). Two patients had two test sessions separated by a single day and, in one patient, multiple testing was carried out over a period of 3 weeks. It is of note that, in three cases, neuropsychological testing was carried out relatively early, i.e. within 4 months of clinical onset.

Neuropsychological findings

Estimated premorbid cognitive functioning

Estimates of premorbid intelligence quotient (IQ) were obtained in 14 cases using the National Adult Reading Test (NART) (Nelson, 1982). These cases had a mean estimated premorbid IQ of 100.4 (range = 75–113).

Summary neuropsychological test indices

Verbal, performance and full‐scale IQ scores from the Wechsler Adult Intelligence Scale—Revised (WAIS‐R) were reported for 16 cases. These cases yielded a mean verbal IQ of 83.6 (range = 68–101), a mean performance IQ of 70.4 (range = 61–88) and a mean full‐scale IQ of 76.3 (range = 62–93). All of the patients obtained performance IQ scores <90. Using norms provided in the WAIS‐R manual (Wechsler, 1981), the mean difference of 13.2 between verbal and performance IQ scores was statistically significant at the 5% level.

Memory functioning

While the results of a variety of memory tests were documented, those that were most commonly given to patients included: orientation for time (day, month, year); immediate and delayed story recall from either the Wechsler Memory Scale—Revised (WMS‐R) (Wechsler, 1987) or from the Adult Memory and Information Processing Battery (AMIPB) (Coughlan and Hollows, 1985); and words and faces recognition memory from the Recognition Memory Test (RMT) (Warrington, 1984). As can be seen in Table 1, most patients showed some degree of anterograde memory impairment. Orientation for time, which includes both an anterograde and retrograde memory component, was impaired in 60% of cases. The test that showed the most consistent deficit was the faces memory subtest of the RMT—all the seven patients who completed this test performed at an impaired level.

Language, verbal reasoning and problem‐solving ability

Table 2 shows the proportion of patients showing mild or marked impairments on verbal subtests from the WAIS‐R, together with performance on the Graded Naming Test (McKenna and Warrington, 1983). As can be seen, deficits were generally mild on these tests and limited to only a proportion of patients. The tests with ∼50% prevalence of deficit included the WAIS‐R information and similarities subtests, and the Graded Naming Test.

Visuoperceptual analysis, non‐verbal reasoning and problem‐solving ability

Many of the performance subtests of the WAIS‐R tap visuoperceptual abilities, and deficits were particularly marked on these subtests. As can be seen from Table 3, most patients showed mild or marked impairments on all of the four subtests that tap visuoperceptual analysis and reasoning (picture completion, picture arrangement, block design and object assembly). Two other tests [the incomplete letters subtest from the Visual Object and Space Perception Battery (VOSP) (Warrington and James, 1991) and the Rey–Osterrieth copying task (Lezak, 1995)] also showed a significant impairment in ∼50% of cases. By contrast, the Benton Facial Recognition Test (Benton et al., 1994) was given to only four patients, and was performed normally by each patient.

Attention/concentration

While elements of attention and concentration are present in most cognitive tasks, for the purposes of this article we have included the following tests under this category: the digit‐symbol and digit‐span subtests of the WAIS‐R; the Speed and Capacity of Language‐Processing (SCOLP) Test (Baddeley et al., 1992); and the FAS Verbal Fluency Test (Lezak, 1995). The scores obtained by vCJD patients are indicated in Table 4. As can be seen, all patients showed a deficit on the WAIS‐R digit dymbol subtest and on the FAS verbal fluency test. Performance on the digit span subtest was relatively intact in most patients. The SCOLP test was only given to five patients, four of whom showed a mild deficit on the test.

Executive function

Formal testing of executive function was seldom reported. Data were available from five patients for the Modified Card Sorting Test (MCST) (Nelson, 1976) and for the Brixton Spatial Anticipation Test (Burgess and Shallice, 1997), and data were available from four patients for the six elements subtest of the Behavioural Assessment of Dysexecutive Syndrome (BADS) (Wilson et al., 1996). On the MCST, four out of five patients showed a mild or marked deficit (Table 5). Three of the four patients who performed the six elements subtest of the BADS were impaired on the test. On the Brixton Spatial Anticipation Test, most patients performed within normal limits, with only one patient showing a marked deficit on the task.

Case reports

vCJD Case 1

Clinical history

This case has been reported in more detail elsewhere (Kapur et al., 2001). The patient was a right‐handed man in his early 20s who presented at the end of July 1998 with a short history of memory difficulties, occasional problems in speech articulation, a change in personality and two episodes of urinary incontinence. His parents thought that the first sign of his illness was evident in May 1998, when he had a slight slurring in his speech during a telephone conversation with them. The first noticeable manifestation of his memory difficulties occurred in early July 1998 when he started a summer work placement and had major limitations in assimilating new information in a computer‐based environment where he was taught simple data entry procedures and, where, during a previous placement, he had excelled. Although he appeared to have no difficulty using equipment around the home (e.g. the video), he performed such activities much more slowly than before. His mother reported that he was very irritable and argumentative when he came home from university in June. He later became indifferent and apathetic. She said that he was often stuck for words and that his speech was sometimes incoherent. He had recently written two letters to his girlfriend that did not make any sense. His mother thought that he was nervous about going out on his own. His condition showed a progressive decline and he died in December 1998.

Neuropsychological findings

During neuropsychological testing, his affect was unusual in that he appeared unconcerned about his situation. At times, he seemed to lack motivation and/or concentration. He tended to use stock phrases such as ‘unfortunately not’ or ‘that’s about it, I’m afraid’ in response to test questions that he was unable or unwilling to answer. Neuropsychological test performance in August 1998 (Tables 6–8) indicated a moderate degree of generalized neuropsychological dysfunction, with particularly poor scores on tests of memory, attention, verbal retrieval, and problem‐solving ability. Areas of spared function included some tests of verbal and non‐verbal reasoning, a complex copying task, picture recognition memory, and faces matching.

vCJD Case 2

Clinical history

The patient was a right‐handed woman in her early 20s who presented in July 2000 with ataxia, hearing problems and cognitive decline. Her symptoms first started when she went to university in October 1999. She developed left hemi‐sensory disturbance, followed by a progressing hearing loss that made it difficult for her to distinguish voices from background noise. She did not return to university after the Easter 2000 break, but instead started work as a waitress. She was unable to cope with this, occasionally burning herself, and suffering from unsteadiness and cognitive difficulties. She became increasingly forgetful, more unsteady and her speech had become slurred. Her parents did not report any significant personality or psychiatric changes as such but found that, towards the end of 1999 and the beginning of 2000, she was becoming rather distressed as a result of her symptoms. Her condition deteriorated until her death in January 2001.

Neuropsychological findings

As can be seen in Tables 6–8, neuropsychological testing showed a moderate degree of fairly generalized cognitive dysfunction. She had impaired performance on tests of story recall, visual design learning, faces recognition memory, words recognition memory, picture recognition memory, verbal reasoning, visual concentration, one test of problem‐solving ability, and tests of verbal fluency and picture naming. She performed normally on copying the Rey–Osterrieth figure, faces matching, and spatial anticipation (Brixton Spatial Anticipation Test). Autobiographical memory was assessed using the incidents component of the Autobiographical Memory Interview (Kopelman et al., 1990). In view of the age of the patient, only childhood memories were tapped. The patient’s score (7/9) was within normal limits.

vCJD Case 3

Clinical history

The patient was a right‐handed man in his early 20s who was first seen in December 2000 with several months’ history of difficulties in balance and speech, together with some sensory disturbance. His mother reported that he had been somewhat withdrawn over the previous year and possibly a little depressed over the past few months. She indicated that over the past year he appeared to tire more easily. A couple of months earlier he had complained of feeling ‘itchy’ all over and of ‘feeling very hot’. She thought that his speech had become slurred over the previous few weeks and that his short‐term memory had deteriorated over the previous few days. The patient himself was not aware of any cognitive limitations and, to specific questioning, he only admitted to some balance difficulties. His condition showed a relentless decline and he died in May 2001.

Neuropsychological findings

On cognitive testing (Tables 6–8), the patient showed a moderate degree of fairly generalized cognitive dysfunction. His impairments were evident on tests of story recall, visual design learning, faces recognition memory, picture recognition memory, words recognition memory, verbal concentration, verbal fluency, visual concentration, spatial anticipation, perceptual motor skill, and picture naming. He performed normally on tests of faces matching and problem solving (BADS six elements test and MCST). On the childhood incidents section of the Autobiographical Memory Interview, the patient performed within normal limits (7/9).

vCJD Case 4

Clinical history

This patient was a right‐handed man in his late 20s who presented in May 2001 with a 6 months history of deterioration in gait and speech articulation. He had collapsed in December 1999, possibly due to anxiety. This occurred in a supermarket and, for the next few months, he was unhappy about going into crowded places. His parents reported that, over the previous 6 months, they had noticed a deterioration in his vision, a slight impairment in speech, occasional word‐finding difficulties and short‐term memory impairment. Around this time, he appeared to have been having some difficulties at work. They also reported that he sometimes seemed to confuse dreams with reality. His parents had further noticed a reduction in his motivation and lack of enthusiasm, and noted that he seemed to tire more easily. He had given up driving because of deterioration in his driving skills and navigational ability. The patient himself had noticed impairments in sensory function, together with pain sensation, in his legs. Over the previous few months before his presentation in May 2001, he had also noticed shaking in his arms, slurring of his speech, some short‐term memory difficulties and deterioration in his vision. His condition continued to progress, and he died in December 2001.

Neuropsychological findings

Neuropsychological testing (Tables 6–8) showed evidence of significant cognitive dysfunction, which was prominent on tests of symbol substitution, verbal fluency, problem‐solving ability, verbal retention and faces recognition memory. He performed normally on tests of words recognition memory, picture recognition memory, picture naming, simple visual perception, verbal knowledge and verbal reasoning. On the childhood incidents section of the Autobiographical Memory Interview, the patient’s score (8/9) was within normal limits.

Discussion

While there was some variability in neuropsychological profiles between cases, the cognitive deficits shown by vCJD patients were particularly evident on tests of memory, on tests of executive function, on tests of attention, and on tests of visuoperceptual reasoning. All patients who received tests of verbal fluency, digit symbol substitution and faces recognition memory showed deficits on these tests. Most patients performed well on tests of basic vocabulary, digit span and verbal reasoning. In four patients who underwent more detailed cognitive testing, there was also evidence of relatively intact long‐term autobiographical memory and faces perception.

The cognitive profile of the patients in this series would appear, at face value, to be somewhat different from that of patients with sporadic CJD, e.g. memory deficits were common, while isolated ‘neocortical’ syndromes such as focal dysphasia or visual disturbance were rare. A recent report of the neuropsychological characteristics in three patients with sporadic CJD emphasized the presence of focal neocortical deficits (Snowden et al., 2002). In addition, patients with sporadic and familial CJD in that study shared a number of characteristics including episodic unresponsiveness together with significant motor and verbal perseveration. These were not the characteristics that we identified in vCJD, and this is perhaps not surprising in view of the very different clinical phenotype in the two conditions. vCJD appears to be characterized by a phase of psychiatric and fairly generalized neuropsychological impairment prior to the development of focal neurological deficits, in contrast to sporadic CJD in which focal neocortical deficits seem to develop early in the clinical course. It is possible that the unresponsiveness and motor perseveration reported by Snowden et al. (2002) may reflect more advanced neurological impairment at the time the neuropsychological testing was carried out. In the four cases reported by Snowden et al. (2002), the assessments were carried out at a mean of >70% of total illness duration compared with 59% of total illness duration in the vCJD cases in this report.

However, the relative scarcity of published neuropsychological test data on patients with other forms of CJD makes any formal comparisons problematical. The wide heterogeneity of sporadic CJD patients, with specific subtypes such as the Heidenhain variant that presents with primarily visual disturbance (Pachalska et al., 2001), is also a factor in any comparisons that are attempted. Compared with one recent neuropsychological case study of sporadic CJD (Zarei et al., 2002), the selective executive dysfunction shown by that patient contrasted with vCJD patients in this series who showed more generalized cognitive dysfunction. It is also worth noting that memory deficits in particular were commonly seen in the vCJD group, while memory was relatively spared in the patient reported by Zarei et al. (2002).

We found that all of the WAIS‐R performance IQ scores of vCJD patients were <90, with performance IQ scores usually well below corresponding verbal IQ scores. Allowing for the limitations of the concept of IQ in clinical neuropsychology (Lezak, 1988) and the fact that performance IQ scores are generally lower than verbal IQ scores in most neurological populations (Lezak, 1995), a consideration of IQ subtest scores does provide possible markers that may help distinguish vCJD from clinically similar conditions. For example, some of the initial clinical features of vCJD overlap with those seen in patients with multiple sclerosis. Most series that have examined IQ scores in multiple sclerosis patients have reported both verbal and performance IQ scores much higher than those which we found in our sample of vCJD patients (Rao, 1986). In the case of verbal–performance IQ contrast, the mean difference of 13.2 that we found was only exceeded in one of the eight studies of multiple sclerosis patients reviewed by Rao (1986). The profile of performance subtest scores does, however, appear to be similar in the two groups of patients, with digit symbol scores being particularly impaired in the vCJD patients reviewed here, and being the lowest scores in six of the eight studies of multiple sclerosis patients reviewed by Rao (1986). In the case of the profile of verbal subtest scores, it is worth noting that whereas digit span was the lowest subtest score in six of the eight multiple sclerosis studies and was lower than scores on the similarities and information subtests in all of the multiple sclerosis groups, digit span was one of the more preserved subtest scores in the profile shown by vCJD patients in our study.

There are inherent difficulties in relating in vivo brain imaging and neuropathological findings at post‐mortem with neuropsychological features of a patient during the course of his/her illness. These are all the more critical when dealing with a rapidly progressive dementia such as that associated with vCJD. Allowing for this reservation, it is notable that the posterior thalamic/pulvinar high signal found on MRI brain scan appears to be one of the characteristic early features of vCJD and has been found in the great majority of cases (Coulthard et al., 1999; Zeidler et al., 2000). The neuropathological correlate of thalamic MRI high signal is probably astrocytosis and neuronal loss, which mostly affects the anterior and medial thalamic nuclei. In view of the fact that some studies have implicated the pulvinar in spatial processing (Karnath et al., 2002; Ward et al., 2002), this may help to explain some of the impairments shown by vCJD patients on non‐verbal visuoperceptual and visuospatial reasoning and problem‐solving tasks. However, it is possible that the motor and/or timed component that was also present in some of these tasks, as in the WAIS‐R performance subtests, may have contributed to the deficits that we found.

The relatively mild loss of memory for autobiographical events seen in four of the cases who underwent more detailed neuropsychological testing accords with a number of other studies on the effects of thalamic pathology (e.g. Nichelli et al., 1988; Peru and Fabbro, 1997), although some instances of marked autobiographical memory loss in patients with thalamic lesions have been recorded (Hodges and McCarthy, 1993). The more generalized nature of vCJD patients’ cognitive impairment is in keeping with the neuropsychological profile reported in cases of dementia associated with thalamic degeneration (Martin et al., 1983; McDaniel, 1990). The executive dysfunction that was evident in this series, coupled with the changes in temperament and motivation that were an early feature of the condition, could be related to the thalamic lesions and to the lesions in the caudate and putamen. All three structures have connections with areas in the frontal lobes. In the case of the thalamic lesions, Pepin and Auray‐Pepin (1993) found frontal hypometabolism in several patients with thalamic amnesia, with corresponding deficits on tests of executive function. The hypometabolism affected the frontal lobes ipsilateral to the thalamic lesions, perhaps due to a disruption of the connections between the lateral dorsal thalamic nuclei and the dorsolateral prefrontal cortex. Although the significant memory impairment that we found is most likely due to the thalamic damage that was evident from an early stage, memory deficits have also been noted after caudate lesions (e.g. Drake et al., 1988). The verbal fluency deficits that we found could also be related to thalamic pathology, but here again other subcortical nuclei, in particular the left caudate, could have been implicated in our patients’ verbal retrieval deficits (Crosson, 1992).

The medial thalamic involvement that has been noted in imaging (Coulthard et al., 1999) and post‐mortem (Kapur et al., 2001) studies of vCJD patients would appear to overlap with that found in alcoholic Korsakoff syndrome, and the presence of deficits in memory and executive function may well relate to the involvement of similar nuclei. However, the degree of memory loss was not in the amnesic range and was therefore less marked than that seen in classical amnesic states associated with Wernicke–Korsakoff patients. At post‐mortem, the thalamic lesion in one single‐case study was found to consist of neuronal loss, affecting both medial and lateral thalamic nuclei (Kapur et al., 2001). Without detailed post‐mortem comparisons. it is difficult to be certain as to the neural mechanisms that may underlie the similarities and differences between the two conditions. It is possible that the more acute nature of the Wernicke–Korsakoff lesion, together with involvement of the mammillary bodies, results in the more severe memory impairment which is seen in that condition compared with what we found in vCJD patients.

The relative sparing of verbal skills, picture recognition memory and autobiographical memory in a number of cases may reflect the relative integrity in the early stages of vCJD of the hippocampal complex and neocortex. Neocortical areas have been implicated in picture memory tasks (e.g. Epstein and Kanwisher, 1998; Sato et al., 1999) and the hippocampal complex is considered to play a key role in the laying down of autobiographical memories and in their retrieval, at least for a limited period of time (Graham, 1999; Moscovitsch and Nadel, 1999).

Although our study was not concerned primarily with the differential diagnosis of vCJD from other young‐onset clinically overlapping neurological conditions, it may be worth briefly considering the differential diagnosis of vCJD vis‐à‐vis such conditions. Perhaps the most common differential diagnosis is with the ‘worried well’, in particular patients who may have non‐specific physical symptoms together with cognitive impairment. One of the cases in our series (Case 2) had in fact been labelled as ‘hysterical’ on the basis of her left‐sided sensory symptoms; this diagnosis was perhaps understandable in view of the clinical and neuroanatomical overlap between psychogenic and neurologically‐based sensory disturbance (Gould et al., 1986; Stone and Zeman, 2001; Vuilleumier et al., 2001). Neurological conditions that may be mistaken for vCJD on the basis of clinical presentation, but where laboratory and imaging investigations may subsequently exclude such a diagnosis, include multiple sclerosis, Whipple’s Disease, progressive multifocal leukoencephalopathy, paraneoplastic encephalitis, Wilson’s Disease, Hashimoto’s encephalopathy, adult‐onset Leigh’s Disease, cerebral vasculitis, subacute diencephalic angioencephalopathy, angiodysgenetic necrotising encephalopathy, intravascular lymphomatosis, gliomatus cerebri, frontotemporal dementia and motoneuron disease (cf. Panegyres, 2001).

In summary, our findings point to the presence of significant neuropsychological dysfunction as an invariable feature of vCJD. The results raise the possibility that the psychiatric abnormalities frequently reported in vCJD patients (Zeidler et al., 1997; Spencer et al., 2002) may be due to the presence of early cognitive deficits that result in emotional and behavioural symptoms, which themselves are a direct or indirect reaction to cognitive difficulties experienced by the patient. As in any retrospective study, but more especially in one where the neuropsychological profile is being described for the first time, caution must be exercised before reaching any definitive conclusions. Differences in variables such as the number and types of tests given, sequence of tests, examiners, etc. may have made some contribution to test performance, in addition to clinical variables such as varying times post‐illness onset that testing was carried out and cognitive assessments mainly being conducted on those patients in whom cognitive difficulties were present. Only a prospective study of vCJD patients, with carefully standardized interview and cognitive testing procedures carried out at specified time periods, will be able to shed light on the possible role of such variables. Nevertheless, it would seem on the basis of this retrospective study that cognitive impairment may represent one of the earliest features of vCJD and that neuropsychological deficits may sometimes precede the onset of psychiatric or neurological symptoms. Our findings may therefore be of some help in the early detection and management of patients with vCJD.

Acknowledgements

We wish to thank the neuropsychologists who allowed us to use their findings in this paper. The National CJD Surveillance Unit is funded by the Department of Health and the Scottish Executive Department of Health.

Fig. 1 Time of neuropsychological assessment in relation to disease onset and death

Fig. 1 Time of neuropsychological assessment in relation to disease onset and death

Table 1

Anterograde memory functioning

Test % impaired 
Orientation (n = 10)  20* 
 Day/month/year 40** 
Immediate story recall (n = 12) <10th percentile 83.3 
Delayed story recall (n = 12) <10th percentile 83.3 
Words RMT (n = 8) <5th percentile 87.5 
Faces RMT (n = 7) <5th percentile 100 
Test % impaired 
Orientation (n = 10)  20* 
 Day/month/year 40** 
Immediate story recall (n = 12) <10th percentile 83.3 
Delayed story recall (n = 12) <10th percentile 83.3 
Words RMT (n = 8) <5th percentile 87.5 
Faces RMT (n = 7) <5th percentile 100 

*Mild impairment (2/3); **marked impairment (1/3 or 0/3).

Table 2

Language, verbal reasoning and problem‐solving

Test Mean Range % impaired 
WAIS‐R verbal IQ (n = 16) 83.69 68–101  
WAIS‐R information (n = 13) 7.23 4–14 53.8* 
WAIS‐R vocabulary (n = 9) 8.22 5–12 22.2* 
WAIS‐R arithmetic (n = 15) 7.2 5–11 26.7* 
WAIS‐R comprehension (n = 7) 8.71 4–13 28.6* 
WAIS‐R similarities (n = 17) 6.82 1–11 47.1* 
   5.9** 
Graded Naming Test (n = 9) 14.78 10–22 44.4* 
Test Mean Range % impaired 
WAIS‐R verbal IQ (n = 16) 83.69 68–101  
WAIS‐R information (n = 13) 7.23 4–14 53.8* 
WAIS‐R vocabulary (n = 9) 8.22 5–12 22.2* 
WAIS‐R arithmetic (n = 15) 7.2 5–11 26.7* 
WAIS‐R comprehension (n = 7) 8.71 4–13 28.6* 
WAIS‐R similarities (n = 17) 6.82 1–11 47.1* 
   5.9** 
Graded Naming Test (n = 9) 14.78 10–22 44.4* 

WAIS‐R: age‐scaled scores were used for all patients; *Mild impairment (age‐scaled score 4–6); **marked impairment (age‐scaled score <4). Graded Naming Test: *mild impairment (1–2 SD below mean of locally developed norms); **marked impairment (>2 SD below mean of locally developed norms).

Table 3

Visuoperceptual analysis, non‐verbal reasoning and problem‐solving ability

Test Mean Range % impaired 
WAIS‐R performance IQ (n = 16) 70.44 61–88  
WAIS‐R picture completion (n = 10) 6.1 3–12 50* 
   20** 
WAIS‐R picture arrangement (n = 10) 5.3 3–8 60* 
   20** 
WAIS‐R block design (n = 15) 5.73 2–8 66.7* 
   6.7** 
WAIS‐R object assembly (n = 7) 2–9 57.1* 
   28.6** 
VOSP incomplete letters (n = 6) 17.7 15–20 50** 
Copy of Rey–Osterrieth complex figure (n = 9) 31.4 24–36 44.4** 
Test of facial recognition (n = 4) 45.5 43–47 All normal 
Test Mean Range % impaired 
WAIS‐R performance IQ (n = 16) 70.44 61–88  
WAIS‐R picture completion (n = 10) 6.1 3–12 50* 
   20** 
WAIS‐R picture arrangement (n = 10) 5.3 3–8 60* 
   20** 
WAIS‐R block design (n = 15) 5.73 2–8 66.7* 
   6.7** 
WAIS‐R object assembly (n = 7) 2–9 57.1* 
   28.6** 
VOSP incomplete letters (n = 6) 17.7 15–20 50** 
Copy of Rey–Osterrieth complex figure (n = 9) 31.4 24–36 44.4** 
Test of facial recognition (n = 4) 45.5 43–47 All normal 

WAIS‐R: age‐scaled scores were used for all patients. *Mild impairment (age‐scaled score 4–6 or 5–10th percentile); **marked impairment (age‐scaled score <4 or <5th percentile). VOSP = Visual Object and Space Perception Battery.

Table 4

Attention/concentration

Test Mean Range % impaired 
WAIS‐R digit symbol (n = 12) (age‐scaled scores) 3.42 1–5 50* 
   50** 
WAIS‐R digit span (n = 16) (age‐scaled scores) 7.87 5–9 18.8* 
Speed of comprehension test (n = 5) (age‐scaled scores) 5.4 4–8 80* 
Verbal fluency: FAS (n = 9) 15.7 3–31 22.2* 
   77.8** 
Animal fluency: FAS (n = 8) 8.75 2–13 12.5*75** 
Test Mean Range % impaired 
WAIS‐R digit symbol (n = 12) (age‐scaled scores) 3.42 1–5 50* 
   50** 
WAIS‐R digit span (n = 16) (age‐scaled scores) 7.87 5–9 18.8* 
Speed of comprehension test (n = 5) (age‐scaled scores) 5.4 4–8 80* 
Verbal fluency: FAS (n = 9) 15.7 3–31 22.2* 
   77.8** 
Animal fluency: FAS (n = 8) 8.75 2–13 12.5*75** 

FAS: norms taken from Spreen and Strauss (1998). *Mild impairment (age‐scaled score 4–6 or 1–2 SD from the norm); **marked impairment (age‐scaled score <4 or > 2 SD from the norm).

Table 5

Executive function

Test % impaired 
MCST (n = 5) 40* 
 40** 
Brixton Spatial Anticipation Test (n = 5) 20** 
Test % impaired 
MCST (n = 5) 40* 
 40** 
Brixton Spatial Anticipation Test (n = 5) 20** 

MCST: *mild impairment (4 or 5 categories with <50% perseverative errors); **marked impairment <4 categories and/or ≥ 50% perseverative errors). Brixton Spatial Anticipation Test: *mild impairment (scaled score = 3); **marked impairment (scaled score < 3).

Table 6

General cognitive test scores

Test Case 1 Case 2 Case 3 Case 4 
WAIS‐R     
Verbal IQ 96 92 88 98 
Performance IQ 71 70 65 88 
Full scale IQ 83 80 76 93 
Subtests (age‐scaled scores)     
 Information 5* 10 
 Digit span (WMS‐R) 
 Vocabulary 12 ‐ 10 12 
 Arithmetic 6* 11 
 Comprehension 10 13 10 10 
 Similarities 11 
 Picture completion ‐ 5* 12 
 Picture arrangement 3** 6* 6* 
 Block design 5* 6* 6* 
 Object assembly 6* 6* 3** 
 Digit symbol 4* 3** 3** 4* 
 NART estimated IQ 107 106 102 112 
 Test of facial recognition  43 (normal) 45 (normal) 47 (normal) 47 (normal) 
 Rey–Osterrieth copy 35 33 24** 33 
 Verbal fluency (FAS) 10** 22** 5** 18** 
 Graded Naming Test  10/30** 16/30* 18* 22 
SCOLP 1–5th percentile** 5–10th percentile* 5th percentile** 25th percentile 
Test Case 1 Case 2 Case 3 Case 4 
WAIS‐R     
Verbal IQ 96 92 88 98 
Performance IQ 71 70 65 88 
Full scale IQ 83 80 76 93 
Subtests (age‐scaled scores)     
 Information 5* 10 
 Digit span (WMS‐R) 
 Vocabulary 12 ‐ 10 12 
 Arithmetic 6* 11 
 Comprehension 10 13 10 10 
 Similarities 11 
 Picture completion ‐ 5* 12 
 Picture arrangement 3** 6* 6* 
 Block design 5* 6* 6* 
 Object assembly 6* 6* 3** 
 Digit symbol 4* 3** 3** 4* 
 NART estimated IQ 107 106 102 112 
 Test of facial recognition  43 (normal) 45 (normal) 47 (normal) 47 (normal) 
 Rey–Osterrieth copy 35 33 24** 33 
 Verbal fluency (FAS) 10** 22** 5** 18** 
 Graded Naming Test  10/30** 16/30* 18* 22 
SCOLP 1–5th percentile** 5–10th percentile* 5th percentile** 25th percentile 

NART = National Adult Reading Test; SCOLP = Speed and Capacity of Language Processing. *Mild impairment (age‐scaled score 4–6 or 1–2 SD from the norm or 5–10th percentile); **marked impairment (age‐scaled score <4 or > 2 SD from the norm or <5th percentile).

Table 7

Anterograde memory test scores

Test Case 1 Case 2 Case 3 Case 4 
WMS‐R general memory quotient 52 86 Not done 67 
WMS‐R delayed memory quotient <50 54 Not done 76 
Verbal memory and learning     
 WMS‐R story recall (immediate) 6th percentile* 7th percentile* <10th percentile* (AMIPB) 2nd percentile** 
 WMS‐R story recall (delayed) 1st percentile** 9th percentile* <10th percentile* (AMIPB) 2nd percentile** 
 WMS‐R verbal P‐A learning (immediate) 4/24** 17/24** Not done 11/24** 
 WMS‐R verbal P‐A learning (delayed) 1/8** 4/24** Not done 7/24** 
 RMT words recognition <5th percentile** <5th percentile** <5th percentile** 10–25th percentile 
Non‐verbal memory and learning   AMIPB design learning  
 WMS‐R designs recall (immediate) 12th percentile 94th percentile  74th percentile 
 WMS‐R designs recall (delayed) 3rd percentile** 5th percentile** A1‐A5; <10th percentile* 14th percentile 
 WMS‐R pattern–colour learning (immediate) 5/18** 18/18 A6; <10th percentile* 11/18* 
 WMS‐R pattern–colour learning (delayed) 6/6 6/6 B; <10th percentile* 6/6 
 RMT faces recognition <5th percentile** <5th percentile** <5th percentile** <5th percentile** 
 Camden Pictorial Recognition Memory Test (Warrington, 1996) 29/30 26/30** 19/30** 29/30 
Test Case 1 Case 2 Case 3 Case 4 
WMS‐R general memory quotient 52 86 Not done 67 
WMS‐R delayed memory quotient <50 54 Not done 76 
Verbal memory and learning     
 WMS‐R story recall (immediate) 6th percentile* 7th percentile* <10th percentile* (AMIPB) 2nd percentile** 
 WMS‐R story recall (delayed) 1st percentile** 9th percentile* <10th percentile* (AMIPB) 2nd percentile** 
 WMS‐R verbal P‐A learning (immediate) 4/24** 17/24** Not done 11/24** 
 WMS‐R verbal P‐A learning (delayed) 1/8** 4/24** Not done 7/24** 
 RMT words recognition <5th percentile** <5th percentile** <5th percentile** 10–25th percentile 
Non‐verbal memory and learning   AMIPB design learning  
 WMS‐R designs recall (immediate) 12th percentile 94th percentile  74th percentile 
 WMS‐R designs recall (delayed) 3rd percentile** 5th percentile** A1‐A5; <10th percentile* 14th percentile 
 WMS‐R pattern–colour learning (immediate) 5/18** 18/18 A6; <10th percentile* 11/18* 
 WMS‐R pattern–colour learning (delayed) 6/6 6/6 B; <10th percentile* 6/6 
 RMT faces recognition <5th percentile** <5th percentile** <5th percentile** <5th percentile** 
 Camden Pictorial Recognition Memory Test (Warrington, 1996) 29/30 26/30** 19/30** 29/30 

AMIPB = Adult Memory and Information Processing Battery. *Mild impairment (age‐scaled score 4–6 or 1–2 SD from the norm or 5–10th percentile); **marked impairment (age‐scaled score <4 or > 2 SD from the norm or <5th percentile).

Table 8

Frontal lobe/executive function test scores

Test Case 1 Case 2 Case 3 Case 4 
BADS Modified Six Elements Test 2** 3* 0*** 
Brixton Spatial Anticipation Test 2** 
MCST 4 categories* 4 categories* 6 categories 3 categories** 
MCST Perseverative Errors 33% 0% 0% 35% 
Test Case 1 Case 2 Case 3 Case 4 
BADS Modified Six Elements Test 2** 3* 0*** 
Brixton Spatial Anticipation Test 2** 
MCST 4 categories* 4 categories* 6 categories 3 categories** 
MCST Perseverative Errors 33% 0% 0% 35% 

BADS: *mild impairment (profile score = 3); **marked impairment (profile score of <3). Brixton Spatial Anticipation Test: *mild impairment (scaled score = 3); **marked impairment (scaled score <3). MCST: *mild impairment (4 or 5 categories with <50% perseverative errors); **marked impairment (<4 categories and/or equal to 50% perseverative errors).

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