J Neurol Neurosurg Psychiatry 1998;65:881–889 881 J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.6.881 on 1 December 1998. Downloaded from Dementia and aphasia in motor neuron disease: an underrecognised association? Wojtek P Rakowicz, John R Hodges Abstract predominantly sporadic, cases have subse- Objectives—To determine the prevalence quently been found in western countries.6–9 and nature of global cognitive dysfunction The most common pattern of cognitive and language deficits in an unselected decline in MND is a progressive dementia of population based cohort of patients with the frontal lobe type.10 It is unclear whether this motor neuron disease (MND). MND-frontal lobe dementia syndrome consti- Methods——A battery of neuropsycho- tutes the extreme end of a range of disease or logical and language tests was adminis- alternatively whether it represents a separate tered to patients presenting consecutively nosological entity. Whereas some early studies overa3yearperiodtoaregional neurol- which looked for intermediate degrees of ogy service with a new diagnosis of cognitive dysfunction in clinically non- sporadic motor neuron disease. demented patients with MND found no evidence of widespread impairment,11 others Results—The 18 patients could be divided reported poor performance in isolated tests of on the basis of their performance into 12 13 three groups: Three patients were de- memory or concentration. The emerging picture is of consistent abnormalities on tests of mented and had impaired language func- so-called “frontal executive” function, most tion (group 1); two non-demented patients notably decreased verbal fluency, aVecting a had an aphasic syndrome characterised large proportion of non-demented patients with Y by word finding di culties and anomia MND. These findings have been taken to indi- (group 2). Major cognitive deficits were cate putative frontal lobe dysfunction, and there therefore found in five of the 18 patients has been some evidence to support this from (28%). The remaining 13 performed nor- 14–16 PET imaging studies. The prevalence of copyright. mally on the test battery apart from these cognitive abnormalities is diYcult to decreased verbal fluency (group 3). ascertain, given the almost complete absence of Conclusions—The prevalence of cognitive prospective community based studies, but a impairment in MND in this population recent hospital outpatient based study has sug- based study of an unselected cohort was gested that up to a third of patients may be higher than has been previously reported. impaired in two or more domains of cognition.17 Language deficits, especially anomia, may In addition to the MND-frontal lobe demen- be relatively frequent in the MND popula- tia syndrome, there are reports of a severe and tion. Aphasia in MND may be masked by rapidly progressive aphasia which can occur in dysarthria and missed if not specifically the absence of major behavioural change.18 19 examined. As with other cognitive deficits it is uncertain (J Neurol Neurosurg Psychiatry 1998;65:881–889) whether these cases represent a distinct sub- http://jnnp.bmj.com/ Department of group as the prevalence of language impair- Keywords: motor neuron disease; dementia; aphasia Neurology, Norfolk and ment in MND has not been systematically Norwich Health Care studied. NHS Trust, Norwich, The aims of our study were, therefore, to According to traditional teaching, cognitive UK examine the prevalence of global cognitive dys- W P Rakowicz deficits do not occur in motor neuron disease function and more specifically language deficits (MND; amyotrophic lateral sclerosis (ALS)). Department of in an unselected population based cohort of The classic picture is one of progressive loss of on September 29, 2021 by guest. Protected Neurology, patients with MND. Based on our previous limb, bulbar, and respiratory muscle function Addenbrooke’s experience we expected to find a proportion of Hospital and MRC caused by the selective degeneration of upper cases with an aphasic syndrome and wanted, in Cognition and Brain and lower motor neurons, sparing the rest of this study, to explore the question of whether Sciences Unit, 1 the nervous system. Nevertheless, there is a they represent one end of a continuum of lan- Cambridge, UK growing literature describing a small pro- W P Rakowicz guage deficits in MND or alternatively a J R Hodges portion of patients with clinically indistinguish- distinct subgroup. A subsidiary aim was to able MND with an overt dementia or aphasic explore the relation between bulbar dysfunc- Correspondence to: syndrome that may even precede the onset of tion and aphasia in MND: because dysarthria Professor J R Hodges, MRC physical symptoms.2 Cambridge Cognition and and muteness have been prominent in previous Brain Sciences Unit, 15 Drawing attention to the association of cases with MND aphasia,18 19 we hypothesised Chaucer Road, Cambridge dementia and MND in the Japanese popula- that aphasia might be overrepresented in CB2 2EF, UK. Telephone tion, Mitsuyama and Takamiya suggested that 0044 1223 355294; fax 0044 patients with bulbar MND. 1223 359062. this might constitute a discrete clinicopatho- logical entity.3 Since then, an increasing Materials and methods Received 6 June 1997 and in number of sporadic and familial cases of SUBJECTS final form 21 May 1998 dementia in the context of bulbar MND have The study patients were recruited from the Accepted 15 June 1998 been described in Japan.45 Similar, although Neurology Department of the Norfolk and 882 Rakowicz, Hodges J Neurol Neurosurg Psychiatry: first published as 10.1136/jnnp.65.6.881 on 1 December 1998. Downloaded from Table 1 Basic demographic data and clinical features of patients with MND Symptom Education duration Symptom Bulbar Patient Age Sex (years) (months) onset Limb UMN Limb LMN Bulbar UMN Bulbar LMN score 148M105L+++ 0 2 72 F 10 24 B + + + + 5 m 366F913B + + + 5m 475M918B+ + + + 3 564M137B++++ 2 6 52 M 10 20 B + + + 5 m 744M105 B + + + 6m 875F913B + + 4m 962M113 L + + + 4 10 74 F 9 10 B + + + 4 11 70 F 9 13 B + + 3 12 54 F 13 17 L + + + 2 13 75 M 9 26 L + + + 2 14 65 M 9 12 B + + + 5 15 81 M 9 6 B + + + 2 16 81 F 9 11 B + + + 5 17 78 F 9 19 B + + + 5 18 75 M 10 14 B + + + 5 Disease duration = time from first symptoms to testing date. Symptom onset: B = bulbar onset; L = limb-onset. Examination findings: UMN = upper motor neuron signs; LMN = lower motor neuron signs; (+) = present; Bulbar score = dys- phagia score (0–3) + dysarthria score (0–3) (see text); m=mute. Norwich Hospital. This is a district neurology CONTROLS service run by three consultant neurologists The performance of patients with MND was and two neurologists in training who see all compared with that of 24 controls in the same outpatient and inpatient referrals to the age range selected from the MRC Applied Psy- specialty from east Norfolk and north SuVolk, chology Unit subject panel. There was no a catchment area of 750 000. Patients with significant diVerence between the patients with suspected MND are admitted as day cases for MND and controls in terms of age (67.3 (SD investigation, including EMG in all cases, and 11.3) years v 69.7 (SD 7.8) years; NS) or edu- recorded in the database of departmental cational level (9.8 (SD 1.3) years v 10.8 (SD activity (MINDEX). 2.3) years; NS). copyright. The study commenced in August 1995. TESTS OF BULBAR FUNCTION Eleven patients with a new diagnosis of MND In the absence of a well validated scale of bul- made between January 1994 and July 1995 bar function a simple scoring system was used were identified from the departmental data- to assess speech and swallowing, each on a base. Their inpatient and outpatient follow up scale of 0 to 3. The two scores were combined files were examined for concordance with El to give an overall “bulbar score” ranging from 0 Escorial research criteria for probable or to 6. 1 definite ALS. A further 14 patients with a Dysarthria scores—0=normal speech; 1=slow diagnosis of probable or definite ALS pre- speech, but fully intelligible; 2=speech intelligi- sented during the course of the study (August ble only with eVort; 3=unintelligible or mute http://jnnp.bmj.com/ 1995 to December 1996) giving a total of 25 Dysphagia scores—0=normal swallowing; patients presenting between January 1994 and 1=unaided swallowing, but slow or with December 1996. The medical records were occasional coughing or choking; 2=still taking reviewed for potential causes of dementia (cer- food by mouth but with significant coughing, ebrovascular disease, alcohol intake, serious choking, or pauses between mouthfuls; 3=feed- head trauma, and significant medical condi- ing via gastrostomy or nasogastric tube. tions) but these were absent in all cases; this NEUROPSYCHOLOGICAL TEST BATTERY was later confirmed with the patients and their on September 29, 2021 by guest. Protected 20 carers. Potential subjects were sent a written Mini mental state examination (MMSE) invitation to participate in the study together Although insensitive to frontal dysfunction, the with a consent form. MMSE is used routinely both clinically and in Four of the retrospectively identified patients research. It is rapid to administer and gives a and three of the prospective group could not be single score out of 30, weighted in favour of tested: three had died, two were mute and orientation. A score<24/30 is generally taken to paralysed, and two declined to be interviewed, indicate dementia. leaving 18 study patients (10 men and eight 21 Dementia rating scale (DRS) women, mean age 67.3 (SD 11.3) years, range The DRS is a more comprehensive cognitive 44–81 years) whose clinical features are given screening battery consisting of five subtests in table 1.