C30 THE CLINICAL SPECTRUM OF COGNITIVE CHANGES IN MND
HODGES JR
Neuroscience Research Australia and University of New South Wales, Randwick, Australia
Email address for correspondence: [email protected]
There is growing evidence for an overlap between MND and Frontotemporal Dementias (FTD) at both a clinical and pathological level. About 10% of patients with FTD develop clinical MND but a much higher proportion have more subtle evidence of motor tract dysfunction. Viewed from a MND/ALS clinic perspective, a significant proportion of people with MND manifest features of FTD (either changes in behaviour/social cognition, higher order cognitive abilities such as planning, organizing and motivation or in language abilities). This talk will concentrate on the later group and outline the range of FTD features that can occur in MND as well as methods of detection and measurement using modern neuropsychological tests. I will draw on the results from a NSW wide survey of 100 patients and caregivers that was recently conducted confirming that there is indeed a high rate of FTD like features in MND, notably apathy, which have a significant impact on caregiver burden. I will also describe a study of cognition and behaviour in consecutive patients attending a MND clinic in Sydney confirming that about a quarter of MND patients fulfill criteria for FTD while a higher proportion have some behavioural and/or cognitive features. The most sensitive task appears to be one directed at inhibitory control that reflects dysfunction of orbitofrontal cortex. These findings clearly have implications for patient management.
C31 MOTOR NEURON DISEASE AND FRONTOTEMPORAL DEMENTIA: THE ROLE OF LANGUAGE DYSFUNCTION
BAK T1, VAN DER HULST D1, ABRAHAMS S1, HODGES J2
1University of Edinburgh, Edinburgh, UK, 2University of New South Wales, Sydney, Australia
Email address for correspondence: [email protected]
Keywords: language, dementia, aphasia
Background: From the very beginning of the scientific description of MND, clinicians identified two forms of cognitive impairment: a full-blown dementia, reminiscent of Frontotemporal Dementia (FTD), and subtle cognitive changes observed in non-demented MND patients (1). Supported by recent discoveries in molecular biology, linking together the pathologies of MND and FTD, cognitive and behavioural changes are now recognised as an important feature of MND (2).
However, several questions remain open (1). Firstly, it is not clear, whether MND/Dementia forms a separate entity, distinguishable from the “classical MND”, or constitutes an end of a spectrum of cognitive changes in MND. Secondly, while it has been recognised that cognitive and behavioural features can occur independently in MND patients (2), the role of language impairment in this context is less clearly defined (3). Finally, questions remain about the relation between MND and FTD. FTD can present in three forms: behavioural variant FTD (bvFTD), Non-fluent progressive aphasia (NFPA) and Semantic Dementia (SD). It has not yet been determined whether MND is associated with a combination of the features of all three, or whether MND/fvFTD, MND/NFPA and MND/SD can occur as separate clinical entities.
Objectives: 1) To compare the cognitive/behavioural profiles of MND/Dementia with non-demented MND patients, with particular emphasis on language dysfunction; 2) to discuss their similarities and differences with the three subtypes of FTD.
Methods: We compared clinical and cognitive data of 20 patients with MND/Dementia and 40 non-demented MND patients from two research centres (Cambridge and Edinburgh), against a background of a thorough literature review, going back to the early 20th Century.
Results: In the MND/Dementia group, all patients showed evidence of language dysfunction, usually taking the form of mutism, with a profound impairment of syntactic comprehension and a particular difficulty in processing verbs/actions. More subtle language impairment was found in the non-demented group. It manifested itself in spelling errors, mild deficits in syntactic comprehension and a semantic deficit characterised by a predominant impairment in understanding of sequential/syntagmatic as opposed to parallel/paradigmatic relationship between actions. Interestingly, this pattern was reversed in the only patient presenting with the clinical picture resembling SD. In both groups, the level of language impairment was not related to the severity of dysarthria, motor and cognitive/behavioural symptoms.
Discussion and conclusions: Language impairment is prominent in both MND/Dementia and in non-demented MND patients. It shares some features but is not identical to any of the three subtypes of FTD. We postulate that language impairment forms an independent clinical feature of MND. Language assessment is, therefore, of central importance to our understanding of MND/FTD.
References
- Bak TH. Annals of Indian Academy of Neurology, 2010; 13:S81–8.
- Strong MJ, Grace GM, Freedman M, et al. ALS, 2009; 10:131–46.
- Bak TH, Hodges JR. Brain and Language, 2004; 89:354–61.
C32 EMOTION PROCESSING IN MND AND FTD
SAVAGE S1, LILLO P1,3, KUMFOR F1,2, HORNBERGER M1,2, PIGUET O1,2, HODGES J1,2
1Neuroscience Research Australia, Randwick, NSW, Australia, 2School of Medical Sciences, The University of New South Wales, Kensington, NSW, Australia, 3Prince of Wales Clinical School, The University of New South Wales, Kensington, NSW, Australia
Email address for correspondence: [email protected]
Keywords: cognition, emotion, frontotemporal dementia
Background: Although initially considered a pure motor syndrome, recent evidence has shown that Motor Neurone Disease (MND) is a multisystem disease which can overlap with frontotemporal dementia (FTD) (1). While only 15% of patients with MND develop frank FTD, up to 50% of cases may exhibit some degree of cognitive impairment (2). Despite the fact that FTD patients experience prominent deficits in emotion perception and social cognition (3), these domains have received relatively little attention in MND, and no study has directly compared FTD and MND patients.
Objectives: The aim of the current study was to investigate basic emotion processing abilities in MND and FTD patients in order to: 1) determine the degree of impairment found in MND patients when processing emotional stimuli, and 2) compare the severity and nature of these impairments in MND and FTD patients when tested on the same measures.
Methods: Twenty-six patients with a diagnosis of MND (13 with co-existing FTD (FTD-MND) and 13 without dementia), 13 behavioural FTD patients and 28 healthy controls completed a battery of neuropsychological and emotion tasks. Cognitive domains included memory, language and executive functions. For the emotion tasks, participants were instructed to select the emotional label associated with black and white photographs of faces, or short video clips of actors portraying basic emotions.
Results: Both MND (n = 26) and FTD patient groups showed significant deficits on the emotion tasks compared to controls. However, after dividing MND patients into those with and without co-existing FTD, only the FTD-MND patients showed significant impairments on measures of emotion, whereas patients without frank dementia performed normally. FTD-MND and FTD patient groups displayed similar levels of impairment on emotion measures, even after controlling for measures of general cognition.
Discussion and conclusions: Patients with MND who also meet clinical criteria for FTD show significant deficits on tests of emotional processing, over and above deficits found on general tests of cognitive function. In this group, disturbance of emotion processing appears to be at least as severe as that seen in patients with FTD. By contrast, MND patients who do not show features of FTD appear to have preserved emotion processing, which clearly has important clinical implications. Specific profiles within the MND groups will be discussed.
References
- Lillo P, Hodges JRH. F Journal of Clinical Neuroscience. 2009;16:1131–5.
- Ringholz GM, Appel SH, Bradshaw M, et al. Neurology. 2005;65(4):586–90.
- Piguet O, Hornberger M, Mioshi E, et al. The Lancet Neurology, 2011;10(2):162–72.
C33 A BRIEF COGNITIVE ASSESSMENT IN AMYOTROPHIC LATERAL SCLEROSIS AND ITS CORRELATION WITH DETAILED NEUROPSYCHOLOGICAL TESTING
HU W, WILSON A, SHELNUTT M, KELLY C, POLAK M, YARAB N, GOLDSTEIN F, KHAN J, GLASS J
Emory University, Atlanta, GA, USA
Email address for correspondence: [email protected]
Keywords: FTLD, language, diagnosis
Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) are neurodegenerative disorders with a shared pathologic feature of neuronal lesions immunoreactive to TAR DNA binding protein of 43 kD (TDP-43). FTLD patients can present with clinical ALS, and ALS patients can develop behavior or language disorders resembling FTLD. ALS patients can also develop cognitive impairment with prominent executive or language deficits short of dementia, and it is thought that cognitive impairment in ALS is mediated through executive dysfunction. We hypothesized that cognitive impairment in ALS can be accurately detected using a brief cognitive assessment, and compared the diagnostic accuracy of this assessment with two other diagnostic measures of cognitive impairment.
Objectives: To determine the prevalence of cognitive dysfunction in a cross-sectional cohort of ALS patients in a multi-disciplinary ALS clinic in a university medical center setting, and to compare the diagnostic accuracy of a brief cognitive assessment based on the Philadelphia Brief Assessment of Cognition with the Frontal Behavioral Inventory (FBI) and detailed neuropsychological analysis.
Methods: Cognitive functions were assessed in 154 ALS patients using a 4-item brief cognitive assessment, including working memory (reverse digit span), letter-guided fluency, oral trails, and delayed verbal recall. The FBI was also administered to each patient's caregiver or study partner. 21 patients underwent detailed neuropsychological analysis to include assessments for verbal and visual learning and recall, along with executive, language, and visual spatial functions.
Results: Among 154 ALS patients (64% women, average age 60.2, S.D. 11.2 yrs) who underwent the brief cognitive assessment, 76 (49%) had impairment in at least one cognitive test (1.5 standard deviation below the mean of healthy subjects). About half (43) had impairment in one test, and 14 had impairments in 3 or more tests. The average FBI was higher among ALS patients with impairments in 3 or more tests (20.8 vs. 9.0, p < 0.016), but high FBI scores were only found in 5/14 of these ALS patients. Among patients who underwent detailed neuropsychological testing (6 with ALS-FTD, 8 with ALS-cognitive impairment but not dementia, and 7 with ALS and normal cognition), impairments in 2 or more tests is associated with 81.0% accuracy in differentiating between ALS-FTD and other ALS patients (compared to 61.9% using the mini-mental status examination). Impairments in confrontation naming were also common among ALS-FTD patients, and were associated with 90.5% diagnostic accuracy in differentiating between ALS-FTD and other ALS patients.
Discussion and conclusion: Executive dysfunction is common in ALS patients, and a brief cognitive assessment can be performed during a busy multi-disciplinary ALS clinic to detect subtle cognitive impairments. Impairments in confrontation naming could occur without fluency impairments, and may be more accurate in predicting extra-motor cortical involvement of TDP-43 pathology in ALS.
C34 THE EYES MAY HAVE IT. EYE-TRACKING AS A BIOMARKER FOR EXTRAMOTOR PATHOLOGY IN ALS
SHARMA R, HICKS S, BERNA C, KENNARD C, TALBOT K, TURNER M
University of Oxford, Oxford, Oxfordshire, UK
Email address for correspondence: [email protected]
Keywords: eye-tracking, extramotor involvement, biomarker
Background: ALS is a multiple system cerebral neurodegeneration for which there is no fully validated diagnostic or monitoring biomarker. The most consistent cognitive deficits relate to executive dysfunction, but traditional neuropsychological assessment is frequently lengthy and may not be a practical or available option for patients, especially those in the later stages of the disease. The oculomotor system involves a network of brain regions that includes areas of the frontal lobes consistently implicated in ALS extramotor pathology. The relative sparing of the brainstem nuclear oculomotor pathways throughout the disease course may be exploited to probe supranuclear pathology by studying oculomotor tasks that depend on intact higher pathways.
Objectives: To explore the potential of eye-tracking as a source of biomarkers for extramotor pathology in ALS.
Methods: Heterogeneous ALS patients (n = 31), PLS patients (n = 5) and age-similar healthy controls (n = 26) were tested using the EyeLink® eye-tracker. The assessment battery included a prosaccade (“look towards”), antisaccade (“look away”), word and picture-cued visual search tasks, and a novel oculomotor version of the Trail-making test (and where possible, the traditional written version for comparison). Participants were also assessed using the revised Addenbrooke's Cognitive Examination (ACE-R).
Results: Both antisaccade latency and error rates were markedly increased in both ALS and PLS patients (p < 0.001) in the absence of a significant difference in either the prosaccade velocity (p = 0.5) or latency (p = 0.7), suggesting supranuclear dysfunction. Antisaccade error rates in PLS patients were significantly higher than in ALS patients (p < 0.05). Both word and picture-cued visual searches were significantly slower in ALS and PLS patients (p < 0.05), supporting frontostriatal involvement. The number of fixations taken before arriving at the target was higher in the word- cued search (p < 0.05). A strong correlation was seen between the written and oculomotor Trail- making test performance in both patients and controls (r2 = 0.7, p = 0.01). Total time to completion of the oculomotor Trail making test, and the number of fixations involved, was significantly higher in both patient groups, with a marked difference between the Trail B versus Trail A performance (p < 0.001), in keeping with executive dysfunction.
Discussion: The antisaccade task and oculomotor Trail-making test were significantly impaired in a heterogeneous group of ALS and PLS patients despite normal prosaccade velocity and latency. This is likely to reflect extramotor pathology. The demonstration of greater impairment in those with PLS raises new questions about extramotor involvement in this sub-group. Potentially, an antisaccade task derived from a portable saccadometer could be easily introduced within neurological centres as part of the diagnostic work-up as well as subsequent monitoring of ALS and PLS patients.
Conclusions: Eye-tracking has significant potential as an objective, quantifiable biomarker of extramotor pathology. Longitudinal validation with structural and functional MRI measures of cerebral involvement, as well as histopathology, is now required.