Elsevier

Neuropsychologia

Volume 38, Issue 6, 1 June 2000, Pages 734-747
Neuropsychologia

Verbal fluency and executive dysfunction in amyotrophic lateral sclerosis (ALS)

https://doi.org/10.1016/S0028-3932(99)00146-3Get rights and content

Abstract

Neuropsychological investigations of amyotrophic lateral sclerosis (ALS) patients have revealed variable results on specific tests, despite a similar overall cognitive profile of predominantly executive dysfunction with some evidence of memory impairment. The most striking and consistent deficit is found using tests of verbal fluency. The current investigation explored why verbal fluency is particularly sensitive to the impairment in ALS, by investigating some of the underlying cognitive processes: (i) intrinsic response generation; (ii) phonological loop functions; and (iii) simple word retrieval. Twenty-two ALS patients and 25 healthy controls were investigated. The battery included: (i) written and spoken letter-based fluency, category fluency, design fluency; (ii) the Phonological Similarities effect and Word Length Effect; and (iii) computerised sentence completion and confrontational naming. The tests were designed to control for motor speed and to accommodate for the range of disabilities that are present in ALS patients. Significant impairments were found on some tests of intrinsic response generation, namely the Written Verbal Fluency Test, Category Fluency Test (generation of animal names) and Design Fluency Test. Phonological loop functions appeared to be intact with evidence of both the Phonological Similarities and Word Length Effects, but the ALS patients displayed significantly reduced working memory capacity. No deficits were found on tests of simple word retrieval. The findings indicate that verbal fluency impairments in ALS patients result from a higher order dysfunction, implicating deficits in the supervisory attentional system or central executive component of working memory, and are not caused or exaggerated by an impairment in phonological loop functions or in primary linguistic abilities. The study also demonstrates the importance of controlling for differences in motor speed, which may have served to exaggerate the presence of cognitive deficits in ALS patients reported by some other studies.

Introduction

Amyotrophic lateral sclerosis (ALS), the most common form of motor neurone disease, is a progressive, ultimately fatal neurodegenerative disorder of unknown aetiology. Traditionally ALS has been viewed as a disease of the motor system, characterised by degeneration of both the upper and lower motor neurones, with no compromise of cognitive functions. Until relatively recently cognitive deterioration was associated exclusively with a subgroup of 3–5% of ALS patients in whom a fronto-temporal dementia occurs [30], [40]. However, a growing number of neuropsychological investigations have now demonstrated selective impairments in executive and memory function in non-demented ALS patients (e.g. [1], [2], [29], [34], [51]).

The most striking and consistently reported cognitive deficit in ALS patients has been demonstrated using the verbal fluency test. Impairments have been shown repeatedly using both spoken letter-based word generation procedures (such as the Controlled Oral Word Association test [1], [17], [20], [21], [33], [34]) and written versions of the test (based on Thurstone’s Word Fluency Test [2], [3], [29]). Category fluency [1] and non-verbal fluency deficits [33] have also been reported.

Variable results have been found on other neuropsychological tests across studies, despite an overall pattern of executive and memory dysfunction. Deficits have been demonstrated on versions of the Wisconsin Card Sorting Test in some studies [2], [14], [17], [34], but not in others [29], [33], [51]. Impairments have also been reported on a range of other tests of executive functions (the Alternating S test, Trail Making Test [22], verbal reasoning [20], [21], picture sequencing [51], random movements of a joystick, Tower of Hanoi [2]), and on tests of visual attention [13], [17], [20], [21], [34], although these procedures have not been employed systematically across studies. In addition some measures of selective attention have also elicited a deficit (negative priming [2] and the Stroop test [17]), although not consistently [29], [33].

The demonstration of memory deficits in ALS has been even more variable. On verbal memory tests, an impairment in prose recall was reported in one study [25], but not in others [14], [22]. Deficits in word list and paired associate learning have been more frequently reported [3], [14], [20], [34], but inconsistently [29], [33] and a word recognition deficit was demonstrated by two recent investigations [2], [17], but not by earlier studies [29], [34], [51]. On visual memory tests, impairments have been revealed in the immediate recall of shapes and designs [17], [20] and of objects [3], [14], [29], but the latter was not replicated by one study [2] and no deficits were shown using standard tests of delayed visual recall [14], [33]. Finally, with a recent exception [17], deficits on tests of visual recognition have not been found [13], [29], [51].

Tests of verbal fluency have been employed traditionally in a clinical setting to measure executive dysfunction. Such procedures involve rapid intrinsic response generation, where responses are minimally specified by external cues or triggers [18], [19], and have been suggested to rely on an intact “supervisory attentional system” (SAS, [42], [48]). Similarly the processes involved in verbal fluency can also be interpreted through Baddeley’s concept of the central executive [4], [5]. Fluency procedures place relatively heavy demands on executive resources [5], with the initiation of effective retrieval strategies to organise thinking and aid generation [16], [32], [54], and the continual switching between retrieval strategies [54].

Verbal fluency also involves the short-term memory of phonological information, which is required to help cue word retrieval and keep track of recent responses [16], [26], [36]. Such memory functions can be interpreted using the concept of the phonological loop, a slave system of working memory [4], [6]. The loop comprises a phonological store within which memory traces fade after about 2 s unless they are revived by articulatory control processes, through subvocal rehearsal.

Successful performance on tests of verbal fluency is also reliant on intact lower order functions of simple word retrieval. Reitan and Wolfson [47] suggest that the verbal fluency impairments reported in patients with frontal lobe damage may simply reflect deficits in language production, as the majority of studies did not control for an aphasic disorder.

The current investigation explored why tests of verbal fluency are particularly sensitive to the impairment in ALS patients, by investigating the cognitive processes which may underlie the deficit, namely executive processes of intrinsic response generation, phonological loop functions and simple word retrieval. The battery included four tests of fluency which all involve rapid intrinsic response generation. Performance on the Written Verbal Fluency Test (on which a deficit in ALS patients has previously been demonstrated [2]) was compared with three other fluency procedures (Spoken Verbal Fluency Test, Category Fluency Test and a non-verbal Design Fluency Test), to determine whether the previously reported deficits in ALS were specific to the type of fluency procedure employed. The functions of the phonological loop in working memory were investigated using two tasks designed by Baddeley and Wilson [7] to dissociate components within the loop. The Phonological Similarities Effect is assumed to reflect the functioning of the phonological store and is based on the finding that normal participants retain sequences of phonologically similar items less well than phonologically dissimilar items. Phonologically similar items are more difficult to retrieve as it is more difficult to discriminate between the phonological codes within the store. The Word Length Effect is assumed to reflect the functioning of the articulatory control processes within the phonological loop. Normal participants retain sequences of long words less well than sequences of short words, because the former take longer to rehearse within the phonological loop, allowing more forgetting between successive rehearsals. Finally, performance on the verbal fluency tests was contrasted with two tests of simple word retrieval (sentence completion test and a confrontational naming test) in which responses were more fully specified by external stimuli and were therefore less reliant on processes of intrinsic response generation.

One of the major problems in conducting neuropsychological investigations of ALS patients is the difficulty accommodating patients’ bulbar dysfunction and/or motor impairments, which exaggerate performance decrements on standard tests. Strong et al. [49] highlighted the problems in assessing language functions in ALS patients with speech impairments resulting from bulbar involvement. Chari et al. [13] addressed this issue by using a computerised battery of non-verbal tests, in which the patients’ sensorimotor capacity was estimated to control for upper limb dysfunction, but they did not use a fluency procedure. The Written Verbal Fluency Test developed by Abrahams et al. [2], [3], and which is employed in the current study, accommodates individual variations in writing speed. Using this method, a significant verbal fluency impairment, which was independent of severity of disability, was demonstrated in a group of 52 non-demented ALS patients [2]. The current battery of tests was similarly designed to control for patients’ physical disabilities in order to provide a clearer profile of the underlying cognitive impairment.

Section snippets

Patients with ALS

Twenty-two patients (12 male, 10 female) with sporadic ALS were recruited from the King’s MND Care and Research Centre. All patients had undergone full clinical assessment under the supervision of one of the authors (PNL). Neurological data were taken from the records of the patients’ clinic visit nearest to the time of testing. All had clinical and electrophysiological evidence of combined upper and lower motor neurone involvement in at least one region. No patient had a history of

Participant characteristics

Comparisons were made between the patient and control groups on a number of background variables and the results are reported in Table 1. The two groups did not significantly differ in age or number of years in education. On measures of intellectual function there were no significant differences between the groups in premorbid full scale IQ as estimated by the NART, the Raven’s SPM score, or in the estimated premorbid Raven’s SPM score. In addition the discrepancy between the actual and

Discussion

The current study investigated whether previously reported verbal fluency deficits in ALS are the result of an impairment in the underlying processes of intrinsic response generation, phonological loop functions or simple word retrieval. The findings revealed a pattern of selective cognitive impairment in a group of ALS patients relative to healthy controls and hence adds to the growing body of evidence indicating extra-motor cerebral dysfunction in ALS (e.g. [1], [2], [17], [29], [34], [51]).

Acknowledgements

Dr Sharon Abrahams was funded by a Wellcome Fellowship during the period of this research. The authors would like to thank Professor Alan Baddeley for his help with the working memory tests. They are also very grateful to Teresa Barby, Keren Down and Dr Matt Parton from the King’s MND Care and Research Centre for their help in recruiting patients. The King’s MND Care and Research Centre is supported by the Motor Neurone Disease Association, UK. Advice on statistical methods was provided by Dr

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