Review articleCognitive change in motor neurone disease/amyotrophic lateral sclerosis (MND/ALS)
Introduction
Classical motor neurone disease/amyotrophic lateral sclerosis (cMND/ALS) has traditionally been assumed to spare cognitive functions. However, there are many historical references to behavioural disorder in MND, and descriptive terms have been applied, ranging from schizophrenia to dementia. A variety of factors compound the interpretation of cognitive abilities, including motor slowing, lack of control of facial and bulbar emotional expression, and the secondary effects of depression, sedative drug intake and hypoventilation. Nevertheless, evidence is accruing from neuropsychological analysis and functional imaging procedures that a proportion of patients with cMND/ALS do have cognitive impairment that is not explicable purely in terms of these confounding variables. Specific dysfunction of the anterior cerebral cortex appears to underlie these mental changes.
A theoretically relevant development in this regard is the observation that a motor neuronopathy arises in a proportion of patients with established frontotemporal dementia (FTD), in which there is degeneration of the frontal and temporal neocortex. This syndrome of FTD/MND is important in that it has potential, in view of its attenuated course, to shed light on the evolution of symptoms in FTD. It points to the earliest neuropsychological deficits and corresponding anatomical changes which precede the spread of pathology and secondary degenerative processes that occur over the course of FTD. Moreover, FTD/MND may have a bearing on understanding of the cognitive changes that arise in cMND/ALS.
This paper addresses the nature of cognitive change in both FTD/MND and cMND/ALS and examines their relationship to neurological findings and type and distribution of pathological change in the brain and spinal cord. Comparisons ought to help to elucidate the nature of the relationship between FTD/MND and cMND/ALS and suggest clues as to why some patients with cMND/ALS appear to develop cognitive impairment, whereas others do not.
Section snippets
FTD/MND
An association between dementia and MND/ALS has been recognized since the early part of the twentieth century [1], and is now well established [2], [3], [4], [5], [6], [7]. The term ‘ALS dementia’ has commonly been adopted to designate the clinical syndrome. Documented clinical information has typically pointed to impairments in frontal lobe function, with reports of character change and behavioural alterations such as social disinhibition being common [4], [5], [8], [9], [10], [11], [12], [13].
Brain-behaviour relationships in FTD and FTD/MND
The pattern of dementia in FTD and FTD/MND is indistinguishable [24]. However, FTD/MND carries out a more localised experiment upon the brain, which can be attributed to its attenuated course: patients with FTD/MND develop bulbar palsy and typically die within 3 years from respiratory failure, whereas patients with FTD may survive as long as 10 or even 15 years. The premature death of patients with FTD/MND may provide clues to the sites of initial change in FTD and the primary structures
Cognitive change in cMND/ALS
Patients with cMND/ALS have difficulty expressing their thoughts and feelings and controlling the emotional aspects of their behaviour because of pseudobulbar and bulbar palsy [27], [28], [29], complicating behavioural analysis. Nevertheless families often comment on alterations in the personality of the patient. Therapists may note a lack of initiative and compliance in occupational and physical therapy, distinguishing patients with cMND/ALS from those with other peripheral neurological and
Memory in cMND/ALS
Memory deficits in cMND/ALS have been demonstrated most consistently on free recall tasks. These have been attributed by some [35] to retrieval failure and inefficient use of learning strategies secondary to frontal lobe dysfunction. Impairments on a visual but not verbal recognition task [35] has also been interpreted in terms of frontal lobe dysfunction on the basis of the greater attentional demands of the visual task. Evidence of deficits in selective attention but not memory function in
Language in MND/ALS
In cMND/ALS several studies have demonstrated impaired performance on language tasks [34], [36], [39], [48], [49], [50], [51], [52], [53], [54]. Most often reported is impoverished word generation, measured by verbal fluency tasks [30], [32], [33], [35], [36], [37], [38], [40], but abnormalities may also be present in other domains, such as sentence comprehension [34], [49] and verb processing [53]. Interestingly, language features largely point to frontal lobe dysfunction. There is evidence,
The relationship beween cMND/ALS and FTD
Functional imaging using SPECT has elicited abnormalities in the frontal and anterior temporal cortices in cMND/ALS, mirroring the pattern of abnormality found in FTD and FTD/MND, albeit to lesser degree [34]. Moreover, frontal lobe abnormalities on imaging can be identified in some patients for whom cognitive deficits cannot be elicited. It has been argued above that orbital frontal cortex represents an early site of pathological change in FTD. Patients with the disinhibited, orbitotemporal
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