P200 THE EDINBURGH COGNITIVE ALS SCREEN (ECAS)
S Abrahams
J Newton
TH Bak
University of Edinburgh, Edinburgh, UK
Email address for correspondence: [email protected]
Keywords: cognition, behaviour, screen
Background: A frontotemporal syndrome occurs in up to 50% of people with ALS. However the cognitive status of the majority remains unknown due to lack of resources and of appropriate screening tools. Here we present the Edinburgh Cognitive ALS screen (ECAS), a 15 minute standardised interview for use by health care professionals in the clinic. The ECAS was developed to be sensitive and specific to cognitive and behavioural changes in ALS and ALS-FTD. The ECAS is unique in being designed; a) specifically for ALS patients with varying motor disability, b) to be sensitive to the range of impairment in ALS including both executive and language dysfunction, c) to distinguish ALS with cognitive impairment from prodromal Alzheimer's Disease and other conditions common in older adults.
Objectives: To demonstrate sensitivity of ECAS to cognitive and behavioural change in ALS.
Methods: 23 non-demented patients with ALS were compared with 20 healthy controls, closely matched for age and years of education. In addition, two cases of ALS-FTD were tested. All participants were interviewed by a nurse specialist. The ECAS is a multidomain interview with sections assessing ALS-specific functions (executive and language) and ALS-nonspecific functions (memory, visuospatial) and a separate carer behaviour interview based on new criteria for diagnosis of behavioural variant FTD.
Results: a) ALS-non demented patients. ALS-specific functions: In total 43% (10) patients showed impairment with 26% (6) a verbal fluency deficit, 22% (5) general executive dysfunction and 26% (6) language dysfunction (spelling impairment). ALS-nonspecific functions: No patients showed a deficit on visuospatial functions. 9% (2) showed memory retention deficit with only, one showing problems with ALS-specific function. Behaviour: 21% of patient carers described changes in behaviour with 17% Apathy, 4% (1 patient) Perseveration and Stereotyped behaviour and 4% (1 patient) with Hyperorality and change in Eating Behaviour. Of note 9% (2 patients) showed behaviour changes without cognitive dysfunction. b) ALS-FTD. ALS-specific functions: the patients were impaired across all elements with prominent executive and spelling dysfunction. ALS-non-specific functions: neither patient was impaired on memory retention. One patient showed poor visuospatial performance. Behaviour: Both patients showed predominant behaviour dysfunction across components.
Discussion and conclusions: This study demonstrates that the ECAS is a sensitive measure of the frontotemporal syndrome in ALS and ALS-FTD. The proportion of non-demented patients detected with cognitive impairment was in line with epidemiological research. Moreover patients showed the pattern of deficits, which is specific to the disease. Of note, one patient showed an independent ALS-nonspecific memory retention problem and it is predicted that this patient has co-morbid prodromal Alzheimer's disease. Further longitudinal and neuropathological findings may provide evidence for this. Future studies will continue to validate this screen.
P201 EXECUTIVE DYSFUNCTION IN ALS RELATES TO REDUCED WHITE MATTER INTEGRITY IN THE FRONTAL LOBES
L Pettit
M Bastin
S Abrahams
University of Edinburgh, Edinburgh, UK
Email address for correspondence: [email protected]
Keywords: cognition, correlation, white-matter
Background: Cognitive impairments are being increasingly recognised as part of the heterogeneous presentation of ALS patients. Deficits in tests of executive functions are the most commonly reported impairment in ALS, however, slowed processing speed, a predominant feature of other motor disorders, has received little attention. Reduced white matter integrity has been shown in tracts and cerebral regions associated with extra-motor functioning, however, direct correlations with cognitive performance are rarely undertaken.
Objectives: This study aimed to determine whether a) cognitive impairments observed in ALS are underpinned by executive dysfunction or slowed processing speed, and b) to identify the loci of white matter changes which may underpin any observed impairments.
Method: Cognitive functioning was investigated in 30 ALS patients and 30 age and IQ-matched controls using tasks designed to account for motor disability. Novel dual-task and processing speed paradigms were designed specifically to test the competing theories of executive functioning and speed. Background neuropsychological tests were also administered. In addition, diffusion tensor magnetic resonance imaging (DTI) data was obtained, allowing measurement of white matter integrity in anterior and posterior cerebral tracts through region of interest measures of fractional anisotropy and mean diffusivity.
Results: ALS patients performed significantly worse than controls in the dual-task and letter fluency test. However, the ALS patients performed comparably to controls on tests of processing speed. Patients’ performance in the dual- task correlated with white matter integrity in the association fibres adjacent to dorsolateral prefrontal cortex. Patients’ performance in letter fluency correlated with white matter integrity in the Genu, and association fibres adjacent to Broca's area and Broadman's area 10.
Discussion and conclusions: ALS patients were impaired on tests of executive functioning, whilst showing intact processing speed. Performance in the dual task and letter fluency test was associated with dysfunction to different pathways within the prefrontal cortex. The ALS group exhibited cognitive impairments indicative of executive dysfunction which were associated with extensive structural white matter changes in the frontal lobes. The investigation of white matter integrity through DTI is a sensitive method for revealing extra-motor changes and heterogeneity within ALS populations.
P202 CORTICAL THICKNESS CHANGES IN ALS WITH OR WITHOUT COGNITIVE AND BEHAVIOR DISTURBANCES COMBINED WITH NEUROPSYCHOLOGICAL ASSESSMENTS
S Ye
D Fan
Peking University Third Hospital, Beijing, China
Email address for correspondence: [email protected]
Keywords: cortical thickness, neuropsychological assessments, cognitive impairment
Background: Some amyotrophic lateral sclerosis (ALS) patients have apparent cognitive and behavior disturbances which meet the criteria of ALS-FTD, and some only have mild symptoms named ALSci or ALSbi. Sensitive neuropsychological examinations can be used for cognitive assessment, and cortical thickness measurement used for learning the structural features.
Objectives: The aim of the study is to discuss the cortical thickness changes in ALS with and without cognitive and behavior disturbances, and find whether there is any correlation between cortical thickness and neuropsychological examinations.
Method: Cortical thickness measurements were performed on structural 3T MRI data of 18 patients and 18 matched healthy controls. Patients would have had tests of verbal fluency, prospective memory, theory of mind and picture emotional perception. Patients were divided into pure ALS, ALSci and ALS-FTD according to the tests and symptoms. Cortical thickness was analysed separately, and the correlation was checked with cognitive examinations.
Result: Cortical thickness of whole brain 70 regions showed no difference between pure ALS patients and controls (P > 0.05). Cortical thickness of bilateral lateral orbitofrontal, bilateral entorhinal, left medial orbitofrontal, and left parsorbitalis cortex were decrease in ALSci. Diffused reduction of cortical thickness was observed in bilateral hemisphere in ALS-FTD. Positive correlations were found between EBPM, TOM, arousal of negative pictures, recognition of pictures and their corresponding brain regions (P < 0.05) .
Discussion: Gliosis might counteract the neuron shrinking, and would lead to no cortical thickness reduction of precentral cortex in pure ALS. Atrophic regions in ALSci could be explained by the cognitive impairments found in patients (using neuropsychological examinations), and we supposed they might relate to the deposition of pThr175-tau. Cognitive and behavior disturbances might be the reason of cortical thickness changes in extra-motor regions, since it was normal in pure ALS. The correlations between neuropsychological examinations and brain regions could all be explained by their anatomic and functional basis. Therefore, we consider that cortical thickness measurements could be used as a sensitive tool to reflect the structural change of cognitive impairment.
Conclusion: Cortical thickness in precentral cortex of ALS patient was not always decreased. Changes of cortical thickness showed a greater difference in pure ALS, ALSci and ALS-FTD, which would help to find the nature of disease. Some neuropsychological examinations had significant relationship with their corresponding brain regions. For those with mild cognitive impairment, cortical thickness measurements could be a sensitive way to assess the cortical structure in an early stage.
P203 SOURCE ANALYSIS OF COGNITIVE FUNCTIONS IN AMYOTROPHIC LATERAL SCLEROSIS PATIENTS BY MEANS OF AUDITORY P300 ODDBALL PARADIGM
A Olivares-Torres1
E Cuspineda-Bravo1
J Iglesias-Fuster2
DM Hernández-Barros2
G Lara-Fernández1
T Zaldívar-Vaillant1
A Soto-Lavastida1
J Gutiérrez-Gil1
J Sánchez-López1
C Pérez-Gesen4
D del Río-Bazán3
C Beltrán1
A Puerta-Armas1
C Machado-Curbelo1
aInstitute of Neurology and Neurosurgery, Havana City, Havana, Cuba
bCuban Center for Neuroscience, Havana City, Havana, Cuba
cHospital Hermanos Ameijeiras, Havana City, Havana, Cuba
dNational Intitute of Endocrinology, Havana City, Havana, Cuba
Email address for correspondence: [email protected]
Keywords: event related potentials, cognitive impairments, source analysis
Background: Traditionally, ALS is considered as a disorder limited to motor neurons in the primary motor cortex, in the brainstem and in the spinal cord, although in recent years, cognitive deficit has been demonstrated in non-demented patients with ALS. Current research has emphasized the usefulness of Event Related Potentials (ERPs) to assess subclinical cognitive impairment. P300 (P3) is the most studied cerebral wave in evaluating cerebral information processing during the course of this neurological disease and several electrophysiological studies provide evidence for extra-motor areas, demonstrating sub-clinical cognitive deficits in patients with ALS.
Objectives: To determine and localize sources of electrical cognitive activities using a P3 auditory stimulation “oddball” paradigm and to investigate the presence of sub-clinical cognitive dysfunction in ALS patients.
Methods: BAEPs were recorded for hearing assessment. P3 component was also recorded in 15 patients with ALS according to a paradigm validated in 25 healthy volunteers using 32 EEG channels. The amplitude and latency for the component obtained were measured. The P3 component was obtained by subtracting the response to the frequent stimuli from that to the infrequent stimuli. P3 Grand Average was computed and electrical sources were estimated by means of Bayesian Model Averaging (BMA) approach in all groups. Clinical variables, depression and cognitive status were also evaluated with standardized scales for all groups.
Results: Normal BAEPs were present in all groups. P3 was not significantly different between patients and healthy controls for latencies, while the amplitude obtained was lower in patients than in controls. In the patient group, P3 amplitude correlated with age of disease onset, time of disease evolution and Beck depression inventory, but it was not related with other severity variables of disease. Significantly lower activation was also found at the level of source generators (postcentral gyrus, superior parietal gyrus, inferior parietal gyrus, and supramarginal gyrus of both hemispheres) in ALS patients as compared with healthy controls.
Conclusions: Decreased P3 amplitude indicates the presence of sub-clinical cognitive deficits in ALS patients. ERPs source analysis is a useful tool in investigating neural substrates and cerebral regions involved in specific cognitive functions. ERPs represent a convenient technique to detect and assess sub-clinical impairment in patients with severe loss of motor function. Our findings confirm the hypothesis of a sub-clinical cognitive impairment in ALS patients, suggesting pathological involvement beyond the motor areas.
P204 THE ACCURACY OF THE MINI MENTAL STATE EXAM IN DETECTING FRONTAL TEMPORAL COGNITIVE IMPAIRMENT IN MOTOR NEURON DISEASE
B Rush
K Mirra
KB Boylan
Mayo Clinic, Jacksonville, FL, USA
Email address for correspondence: [email protected]
Keywords: cognitive screening, diagnostic validity
Background: The Mini Mental State Exam (MMSE) is used routinely in clinical practice and research of patients with motor neuron disease (MND) despite recognized limitations for evaluating frontal temporal cognitive impairment common in MND. The ALS Cognitive Behavioral Screen (ALS-CBS) was developed specifically for screening frontal temporal cognitive impairments in MND and has published diagnostic validity data for examining such symptoms in MND. The diagnostic accuracy of the MMSE and a MND-specific screening tool has never been directly compared in a sample of patients with MND.
Objectives: To compare the diagnostic accuracy, sensitivity, and specificity of the MMSE and the ALS-CBS in detecting frontal temporal impairment in MND.
Methods: Fifty patients with MND were administered the MMSE, the ALS-CBS-Cognitive Scale, and an independent comprehensive neuropsychological evaluation. Neuropsychological evaluation findings were used as the gold standard for classifying patients into 3 diagnostic groups: Normal, Mild Cognitive Impairment (MCI), and Dementia. Using accepted cut-off scores for the MMSE and ALS- CBS, diagnostic accuracy of the screening measures was evaluated in distinguishing between patient groups.
Results: Neuropsychological evaluation yielded 10 Normal, 19 MCI, and 21 Dementia cases. Kruskal-Wallis and Mann Whitney U tests revealed no significant group differences in patient demographics or disease characteristics. Kruskal- Wallis tests revealed predicted group effects for MMSE (χ2 (2, N = 50) = 24.9, p < 0.0001) and ALS-CBS-Cognitive Scale (χ2 (2, N = 50) = 34.0, p < 0.0001). Scores were: MMSE (Normal (median = 29.1; IQR 28.6, 29.3)); MCI (median = 27.9; IQR 26.1, 27.9); Dementia (median = 24.0; IQR 20.6, 26.1)] and ALS-CBS-Cognitive Scale (Normal (median = 16; IQR 15, 17.3); MCI (median = 12; IQR 10, 14); ementia (median = 7; IQR 4.5, 8)). In distinguishing Normal from Dementia patients using accepted cut-off scores for MMSE (< 23) and ALS-CBS-Cognitive Scale (< /= 10) the MMSE had a diagnostic accuracy of 58% (Sensitivity = 38%; Specificity = 100%) compared to 90% for the ALS-CBS-Cognitive Scale (Sensitivity = 86%; Specificity = 100%). In distinguishing Normal from MCI/Dementia patients, using accepted cut-off scores for MMSE (< 26) and ALS-CBS-Cognitive Scale (< 17) the MMSE correctly identified 58% (Sensitivity = 48%; Specificity = 100%) compared to 86% with the ALS-CBS-Cognitive Scale (Sensitivity = 98%; Specificity = 40%). Uniformly, false negative screening errors were more common using the MMSE than the ALS-CBS Cognitive Scale.
Discussion: The MMSE has limited accuracy in detecting frontal temporal cognitive impairment in MND. Using the MMSE for cognitive screening in MND may inflate false negative screening errors and consequently preclude early identification of MND patients with cognitive impairment. Findings question the validity and utility of the MMSE as a cognitive screening tool for patients with MND and support the use of screening tools designed and specifically validated for use in MND.
P205 MEMORY FUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS IN COMPARISON TO PATIENTS WITH MILD COGNITIVE IMPAIRMENT: A NEUROPSYCHOLOGICAL AND STRUCTURAL ANALYSIS
J Machts1
J Kaufmann3
N Naue1
E Kasper2
C Schuster2
J Prudlo2
S Petri4
K Kollewe4
R Dengler4
S Abdulla3
C Stoppel3
E Düzel1
D Bittner3
S Vielhaber1
eGerman Centre for Neurodegenerative Diseases, Magdeburg, Germany
fGerman Centre for Neurodegenerative Diseases, Rostock, Germany
gDepartment of Neurology, Otto-von-Guericke University, Magdeburg, Germany
hDepartment of Neurology, Hannover Medical School, Hannover, Germany
Email address for correspondence: [email protected]
Keywords: memory functions, cognition, structural MRI
Background: Cognitive functions have been found to be deficient in patients with amyotrophic lateral sclerosis (ALS), but unlike in patients with mild cognitive impairment, where temporal dysfunctions are assumed to cause the deficits, the role and characteristics of memory impairment in ALS remain unclear.
Objectives: Define and compare memory functions in ALS patients with a group of amnestic MCI patients (aMCI) using a neuropsychological assessment and structural MRI analysis.
Methods: 40 ALS-Patients, 40 amnestic MCI patients and 40 healthy age- and gender-matched controls were subjected to perform neuropsychological tests. In addition structural MRI was acquired and analyzed using voxel-based morphometry (VBM).
Results: The analysis of the verbal memory performance (measured with Auditory Verbal Learning Test) revealed the following pattern: The aMCI group showed a significantly poorer performance in the delayed verbal recall compared to ALS patients and healthy controls (p < 0.01). Similar effects were observed in the recognition task. Amnestic MCIs recognized a significantly lower amount of previously presented words than the group of ALS patients and healthy controls while ALS patients made more errors during the recognition. After error correction of the recognition performance, there were significant differences between the ALS group and the healthy controls (p < 0.05). Analyzing the structural data we found both temporal and frontal atrophies in the ALS patients in correlation with the above mentioned results.
Conclusion: Memory impairment is evident in patients with ALS. While aMCI patients suffer from a mainly hippocampal dysfunction, memory impairment in ALS patients appears to be linked to fronto-temporal dysfunctions. This is supported by neuropsychological and structural changes observed in the MRI and could be a relevant factor for the progression of the disease.
P206 LANGUAGE IMPAIRMENT IN ALS: PREVALENCE, PROFILE AND RELATION TO EXECUTIVE DYSFUNCTION
L Taylor1
RG Brown1
S Tsermentseli2
A Al-Chalabi3
CE Shaw3
CM Ellis4
PN Leigh5
LH Goldstein1
iDepartment of Psychology, Institute of Psychiatry, King's College London, London, UK
jUniversity of Greenwhich, London, UK
kDepartment of Clinical Neuroscience, Institute of Psychiatry, King's College London, London, UK
lKing's College Hospital NHS Foundation, London, UK
mBrighton and Sussex Medical School, University of Sussex, Brighton, UK
Email address for correspondence: [email protected]
Keywords: cognition, executive dysfunction, language
Background: Executive dysfunction has been the most frequently investigated cognitive domain in non-demented ALS patients. Studies have frequently reported impairments in fluency, set-shifting, attention and inhibition. Recent consensus criteria(Citation1) have defined cognitive impairment in ALS based on impaired scores (≤ 5th percentile of age- and education-matched controls) on at least two measures of executive functioning, although cognitive impairments observed in ALS patients are not restricted to the executive domain. Studies have reported impairments on tasks of language function including confrontation naming, single word and syntactic comprehension and verb processing. However, there have been comparatively few systematic investigations of language in non-demented ALS patients and the nature and frequency of language impairment has not been fully characterised. Where impairments have been identified, it remains unclear whether they reflect an aphasia-like impairment or a primary executive dysfunction.
Objectives: The current study aimed to investigate the prevalence and nature of language involvement in non-demented patients with ALS and examine whether language impairments can be sufficiently explained by executive dysfunction.
Method: Neuropsychological assessment data was obtained from 51 patients with ALS and 35 healthy controls matched for age, gender and IQ. Composite scores were derived for the domains of language, executive, memory and visuospatial functioning. Domain impairment was defined as a composite score ≤ 5th percentile relative to the control mean.
Results: Analysis revealed that the ALS patients demonstrated significant impairments in domains of executive and language functioning compared to healthy control participants, with significantly lower composite scores indicating poorer performance. Language impairment was found in 43% of ALS patients, and Executive impairment in 31% of patients. The ALS patients demonstrated impairments in naming, comprehension and verb processing. Inspection of individual participants’ performance revealed no single pattern of language impairment.
Language impairment was related to the degree of executive dysfunction; we found a significant correlation (p < 0.001) between language and executive composite scores. Executive functioning emerged as a significant predictor of language performance in the ALS patient group, accounting for 44% of the variance in the Language composite scores (p < 0.001). However, > 40% of patients classified as impaired on the language composite demonstrated executive abilities within the unimpaired range.
Discussion and conclusions: This study demonstrates that language impairments may be at least as prevalent as executive dysfunction in ALS. Results highlight that language and executive impairments are a frequent, but not consistent feature of cognitive change in ALS. Although executive and linguistic symptoms may co-occur, linguistic deficits can occur in isolation of wider cognitive change and cannot be sufficiently explained by frontal-executive dysfunction, further highlighting the heterogeneity of cognitive impairment in ALS patients.
Acknowledgements: Support was obtained from the MRC, MND Association UK and Institute of Social Psychiatry
References
- Strong MJ . ALS. 2009;10:131–46.
P207 THE BENEFIT OF USING BOSTON NAMING TEST SCORES TO CHOOSE COMMUNICATION INTERVENTION
E Sandin1
H Ljungman1
P Östberg2
nUniversity Hospital, Uppsala, Sweden
oUppsala University, Uppsala, Sweden
Email address for correspondence: [email protected]
Keywords: communication, Boston Naming Test, augmentative and alternative communication
Background: The Boston Naming Test (BNT) measures confrontational word retrieval in individuals. A comparison between patients in our clinical program with ALS/MND (n = 15) with a control group (n = 15) concerning subtle language disorders, showed significant differences (p < 0.004) between the results for the two groups on BNT (items 29–58).
Objectives: We wanted to examine if the shorter version of BNT might give us information about the lexical level of the patients and by that give us information about accurate communication intervention procedures such as different types of Augmentative and Alternative Communication (ACC).
Method: We included the shorter version of BNT in our standard clinical procedure. All ALS/MND patients joining our program at the Uppsala University Hospital, Sweden, were offered the opportunity to be examined by BNT (items 29–58; a total of 30 items). We compared the results between BNT scores among patients with already implemented ACC together with the most accurate ACC solutions for new patients. The BNT procedure was replicated no shorter than every sixth months.
Results: During March 2010 - April 2012 we examined 51 patients between one to four different occasions with the described short version of BNT. Over 90% of the intrapersonal scores were consistent (+/2 3 items). We examined 20 patients with moderate or severe dysarthria/anarthria among patients with ALS/MND with bulbar and/or higher motor neuron involvement. Three of the patients were offered ACC but denied. Two have BNT- scores < 14/30: Both use low-tech communication aids such as picture pointing or answering questions by yes/no. Six patients who scored between 16–22/30 use a mixed form of ACC with communication by a Light Writer SL35 or Speak Out, writing, pointing at pictures and letters, using a “subject chooser” or scanning by help from a significant other. Three of the six patients have whole or partially computer based communication. Nine patients scored > 22/30 and seven of these use whole or partially high-tech communication solutions such as Light Writer SL40, computer based communication through eye control or head mouse. In this high-score group there is a broader prevalence of mixed communication aids and strategies compared to the other groups. Out of the 31 patients without communication impairments we found seven patients with BNT-scores < 17/30.
Discussion: In spite of a limited group of patients we have found that BNT scores might give us an additional explanation for why some patients receive low-tech communication aids and some high-tech. By additional planning out of BNT-scores the ALS/MND patients gain more accurate communication intervention and time.
Conclusion: BNT is a helpful and easy administrated procedure that gives information which helps in choosing an accurate level of ACC on a personal basis.
P208 A NEW TOOL TO MEASURE PATHOLOGICAL LAUGHING AND CRYING IN ALS
J Murphy
Y-N Duong
F Ahmed
C Lomen-Hoerth
University of California San Francisco, San Francisco, USA
Email address for correspondence: [email protected]
Keywords: pathological laughing and crying, PBA, emotional
Background: Pathological Laughing and Crying (PLC) expresses itself as uncontrolled, unwanted emotional displays of crying and laughing and patients with Amyotrophic Lateral Sclerosis (ALS) have among the highest documented prevalence rates of PLC. The recent FDA-approved medication Neurodex has been a successful treatment option for ALS patients with PLC symptoms. Despite this advancement, our understanding of the subjective experience of PLC remains limited. The Pathological Laughing and Crying Experience Survey (PLACES) is introduced as a tool to measure patients’ internal experiences of PLC, in the hope that a closer examination of the prevalence and nature of PLC will advance understanding of the anatomy of PLC, assist in identification of affected patients, and more broadly inform our understanding of emotion regulation.
Objectives: Identify the prevalence of PLC in the ALS population and validate this new tool's utility, when used with currently existing measures of PLC.
Methods: This study employed two self-administered questionnaires with ALS patients, to measure the prevalence and clinical phenomenon of PLC. The CNS-LS, a 7-item scale, identified objective levels of clinical PLC. The PLACES is an 18-item self-report likert scale that documented patients’ subjective and objective experience of pathological laughing and crying episodes. Individual items measure patients’ subjective experience of controllability of episodes, mood congruence, episode triggers, onset characteristics, and the duration, frequency, intensity, and type of emotional outbursts.
Results: Participants (N = 230) with confirmed ALS reported varying levels of PLC (7–33) with 35.6% reporting clinically significant levels, as indicated by a CNS-LS score of greater than or equal to 13. Of those patients with clinical levels of PLC participating in a larger study (N = 44), patients reported a preponderance of crying (52%), as opposed to laughing (24%), or equal amounts of each (24%). Male patients reported higher levels of uncontrollable laughter than did females (F = 6.4; p = 0.01), yet males and females had equal levels of crying frequency. Patients reported that both laughing and crying episodes were triggered most of the time by emotional precedence, thus they were not spontaneous. The duration of laughing episodes was shorter than crying spells, lasting only a few minutes or less, and was less congruent with pre-existing mood. Crying episodes tended to be more congruent with pre-existing mood.
Discussion: Negative emotions experienced during PLC episodes may be more authentically felt than previously suspected, being rooted in pre-existing feelings and being difficult to control. Interesting gender differences in laughing episodes warrant further study.
Conclusion: PLC in ALS patients is important to identify and treat, particularly because this common and distressing syndrome has the potential for being effectively treated.
P209 BRAIN COMPUTER INTERFACE AND EYE-TRACKING TECHNOLOGY FOR NEUROPSYCHOLOGICAL ASSESSMENT OF ALS PATIENTS
L Carelli1
B Poletti1
F Solca1
P Meriggi2
P Cipresso3
E Pedroli3
S Messina1
C Morelli1
D Lulé4
AC Ludolph4
G Riva3
V Silani1
pDepartment of Neurology and Laboratory of Neuroscience, “Dino Ferrari” Center, Università degli Studi di Milano, IRCCS Istituto Auxologico Italiano, Milan, Italy
qPolo Tecnologico, Biomedical Technology Department, Fondazione Don Carlo Gnocchi Onlus, Milan, Italy
rApplied Technology for Neuro-Psychology Lab, IRCCS Istituto Auxologico Italiano, Milan, Italy
sDepartment of Neurology, University of Ulm, Ulm, Germany
Email address for correspondence: [email protected]
Keywords: cognitive assessment, brain computer interface, eye-tracking
Background: Most Amyotrophic Lateral Sclerosis (ALS) patients show a range of cognitive deficits, with 5% presenting clinical features of frontotemporal dementia (Citation1). Cognitive assessment in moderate-severe stages of ALS may become problematic, due to the lack of motor-verbal free testing. Eye-tracking (ET) and Brain Computer Interface (BCI) have been effectively used in ALS as Alternative and Augmentative Communication means and represent interesting tools to administrate extended neuropsychological assessments.
Objectives: A recently funded project, “eBrain: BCI-ET for ALS”, aims to evaluate P300 BCI and ET technology as cognitive assessment tools in ALS. To preliminary test this approach, a widespread used and sensitive cognitive task, the Verbal Fluency test (VF), has been administered to a sample of healthy subjects. The overall project testing setup has also been evaluated for successive clinical use.
Methods: Twenty-eight healthy subjects (M. age: 55 ± 14 years, M. education: 14.35 ± 3.68 years) underwent a two-hour session, including the systems calibration, a words copy task and VF with BCI and ET. In the ET assessment, the VF has been administered according to the original procedure (three one minute phonemic and semantic VF). In the BCI, subjects have been asked to produce a word starting with the “M” letter and then to write it by means of BCI, for five times; the total reasoning time has been computed. A short neuropsychological screening has also been performed.
Results: The average BCI calibration accuracy was 92.74%. In the BCI copy test, correctly selected characters were about 80% (M. 11,12 over 14); in the VF, subjects correctly written about 88% of characters (M. 24.04 over M. 27.5), with an average reasoning time of 17.5 seconds for producing five words. For the ET assessment, correctly selected characters in the copy test were about 94% (M. 30.07 over 32); in the VF, subjects correctly written about 95% of characters (M. 32.6 over M. 34.40).
Discussion and conclusions: These preliminary results show a good rate of accuracy for both BCI and ET systems, without a preliminary training. VF in BCI required not trivial changes in the original procedure, while ET allowed a reasonable adherence to the original validated test. However, BCI could be more suitable in the presence of eye movement's alterations. The definition of ALS patients’ cognitive profiles has a major importance for clinical issues and patients end-of-life decisions. The study presents the use of BCI and ET as possible means for the development and administration of a motor-verbal free neuropsychological battery. This protocol will be also applied to ALS patients, by adapting other cognitive tests to these technologies in order to obtain a more comprehensive cognitive battery.
References
- Phukan J, Pender NP, Hardiman O. Lancet Neurology 2007;6:994–1003.
P210 FORCED VITAL CAPACITY, NEUROPSYCHOLOGICAL IMPAIRMENT, AND AMYOTROPHIC LATERAL SCLEROSIS
D Harris
J Eppig
C Nieves
A Deboo
M Paolone
T Heiman-Patterson
D Libon
Drexel University College of Medicine, Philadelphia, PA, USA
Email address for correspondence: [email protected]
Keywords: FVC, neuropsychological, ALSFRS
Background: Forced vital capacity (FVC) is an integral and important parameter used to track and evaluate patients with MND/ALS. Previous research has linked reduced FVC with cerebral perfusion deficits in ALS. Given that decreased perfusion could result in cognitive dysfunction, there may also be a link between reduced FVC and neuropsychological deficits.
Objective: To examine the relationship between neuropsychological deficits and FVC in ALS.
Method: 32 patients diagnosed with definite and probable ALS. Patient characteristics were: 40.5% were female, 59.5% were male, M age = 62.36 (11.36); M education = 13.74 (2.35); MMSE = 27.16 (2.93); M length of illness = 4.56 (6.54); M ALS-FRS = 28.69 (11.23); and M FVC = FVC: 65.64% (23.85). Neuropsychological functioning was assessed with the Philadelphia Brief Assessment of Cognition (PBAC), brief assessment of neurocognitive functioning measuring executive control, language, visuospatial functioning, verbal/ visual memory and behavior/ comportment. The mean total PBAC score was 73.82 (10.94), a score well above the cut-off for dementia. Using simple correlation and multiple regression analyses, the combined association between FVC, neuropsychological impairment, and functioning abilities assessed with the ALS Functional Rating Scale (ALS-FRS) were examined.
Results: Simple correlations found better FVC was related to better performance on the PBAC executive Index (r = 0.435, p < 0 .004); language Index (r = 0.428, p < 0.009); visuospatial Index (r = 0.353, p < 0.026); and the total the PBAC score (r = 0.452, p < 0.006); and ALS-FRS bulbar (r = 0.554, p < 0.001; upper limb (r = 0.427, p < 0.003; lower limb (r = 0.519, p < 0.519), and respiratory (r = 0.310, p < 0.038) functioning. A regression analysis was conducted with FVC as the dependent variable. In the first block, all five PBAC neurocognitive indices were entered using a stepwise procedure. Only the PBAC executive index entered the model, accounting for 39 percent of variance (r = 0.619, R2 = 0.383, F = 19.21, df = 1/31, p < 0.001). In the second block, all ALS-FRS indices were entered also using a stepwise procedure. The ALS-FRS index measuring lower limb functioning entered first (r = 0.770, R2 = 0.593, F = 15.48, df = 1/30, p < 0.001), followed by ALS-FRS bulbar index (r = 0.770, R2 = 0.666, F = 6.30, df = 1/29, p < 0.018). The entire model accounted for 66 percent of the variance.
Discussion: In prior research ALS severity, operationally defined with the ALS-FRS and FVC, correlated with reduced cerebral perfusion in frontal/ parietal brain regions assess with arterial spin labeling (ASL). The current research found an association between executive function and ALS-FRS lower limb followed by bulbar functioning suggests that FVC might be used to estimate cerebral functioning in ALS patients.
P211 DIFFERENTIAL NEUROPSYCHOLOGICAL IMPAIRMENT ASSOCIATED WITH BULBAR ONSET AND INVOLVEMENT IN AMYOTROPHIC LATERAL SCLEROSIS
L Elman1
L Mccluskey1
A Boller1
M Grossman1
D Libon2
tUniversity of Pennsylvania, Philadelphia, PA, USA
uDrexel University College of Medicine, Philadelphia, PA, USA
Email address for correspondence: [email protected]
Keywords: executive dysfunction, bulbar disease
Background: ALS patients with bulbar onset typically have a poor prognosis though prolonged survival may occur. Dementia and executive dysfunction are additional poor prognostic factors in ALS. There remains controversy as to whether bulbar onset disease is associated with an increased incidence of executive impairment.
Objectives: To test the hypothesis that bulbar involvement in ALS patients will be related to greater neuropsychological impairment.
Methods: A group of approximately 200 patients were seen at the ALS Association Center at the University of Pennsylvania and participated in ongoing longitudinal research (M age = 61.13 + 13.05; M education = 14.31 + 3.40; M MMSE = 28.45 + 2.53). Data regarding 1) the site of disease onset; and 2) the presence or absence of upper motor neuron (UMN) and lower motor neuron (LMN) disease by segment was collected. Neuropsychological assessment included a letter F-fluency test, digits forward/ backward, The Oral Trails Test, and a modified Visual-Verbal Test; not all tests were administered to all patients. The effect of initial segment involvement at disease onset (bulbar, cervical, lumbosacral) was assessed with a series of 1-way ANOVAs.
Results: When compared to patients with cervical or lumbosacral onset, patients with bulbar onset disease presented with lower performance on the digits backward and Visual-Verbal tests (digits backwards F(2/154) = 4.17, p < 0.017; Visual-Verbal Test (F(2/97) = 3.82, p < 0.025). Post-hoc analyses found that bulbar onset disease patients repeated fewer digits backward compared to patients with cervical onset disease (p < 0.012) and scored lower on the Visual-Verbal Test compared to cervical onset (p < 0.032) and lumbosacral onset (p < 0.048) patients. Groups were then constructed on the basis of presence or absence of UMN and/or LMN signs for all three segments. T-tests comparing patients with UMN bulbar disease versus no UMN bulbar disease found worse performance on tests of letter F-fluency (t(184) = 2.38, p < 0.018), digits backwards (t(174) = 2.05, 0.042) and Oral Trails (t(157) = 2.84, p < 0.005). Similar t-test compared for the presence or absence of UMN and LMN cervical and lumbosacral signs revealed no differences on neuropsychological tests.
Discussion: In a large cohort of ALS patients, bulbar onset disease and bulbar involvement, and particularly UMN bulbar involvement, appears to result in differential neuropsychological impairment when compared to other groups of ALS patients.
Conclusions: Longitudinal research, currently underway, will address whether bulbar onset and the presence of UMN bulbar signs are differentially related to the cognitive impairment throughout the disease course.
P212 GENDER DIFFERENCES IN THE BEHAVIORAL VARIANT OF FRONTOTEMPORAL DISEASE (BVFTD) IN AMYLOTROPHIC LATERAL SCLEROSIS: A NATIONAL SAMPLE
C Flaherty-Craig1
A Brothers2
A Mcfalls1
M Harrison1
C Yang1
R Legro1
Z Simmons1
vPenn State College of Medicine, Hershey, PA, USA
wUniversity of Colorado, Fort Collins, CO, USA
Email address for correspondence: [email protected]
Keywords: FTD, gender, remediation
Background: We recently demonstrated gender differences in emergence of frontotemporal disease (FTD) associated cognitive decline in a national sample of 110 ALS subjects(Citation1). Female gender was associated with more bilateral involvement of cognitive change, with relatively greater preservation of language capacities, consistent with cognitive reserve theory. Currently, we hypothesize that female gender is associated with a less florid, more apathetic profile in ALS in the course of emerging behavioral change, consistent with more frontal cortical-subcortical involvement.
Objectives: Our objectives were to investigate gender differences in prevalence rates and pattern of emergence of change in the three recognized subtypes of behavioral impairment (bi) in ALS: disinhibited (DIS), apathetic (APA) and stereotypic (STE)(Citation2).
Methods and materials: A convenience sample of 114 subjects (56 M) from 14 ALS multidisciplinary clinics were evaluated cross-sectionally by completion of the 24 item Frontal Behavioral Inventory (FBI), a caregiver based interview rating of behavioral change with scores ranging from 0–3. Based upon Neary et al. classification(Citation2), 5 FBI items were combined for each behavioral subtype. This allowed for a range of scores from 0–15, while data for each gender was skewed due to the mild degree of behavioral change evidenced by most subjects. Thus, the non-parametric Mann-Whitney U was applied to compare gender group findings. Demographic comparisons were made with t-tests.
Results: Gender groups were equivalent for education and IQ, the female group expectedly older(p = 0.006). Prevalence rates of clinically evident behavioral change (FBI Total > 27) were small for the total sample (4.1%) and equivalent between gender groups (p = 0.234). No gender differences were evident for the APA and STE subtypes, while a significantly greater proportion of males evidenced the DIS subtype(p = 0.002).
Discussion and conclusions: Consistent with the tendency to mask cognitive change in emerging FTD(Citation1), female gender appears to be associated with a more covert type of behavioral change in the early stage. Ironically, this is recognized to be associated with more widespread frontal pathology extending into the dorsolateral convexities of the frontal lobes(Citation2). We propose a remediation approach based upon a neuroendocrine model purporting the use of estrogen as an effective intervention strategy to impede both the declines in cognitive capacities and behavioral activation evidenced in female ALS patients with emergence and progression of FTD. We plan to test this neuroendocrine model in a multicenter clinical trial involving FTD patients in the presence and absence of ALS, in a crossover design.
References
- Flaherty-Craig C, Brothers A, McFalls A, Yang C, Simmons Z. Neurodegenerative Disease Management, accepted for the June issue 2012.
- Neary D, Snowden J, Mann D. Journal of Neurological Sciences 2000;180:15–20.
P213 NARRATIVES OF ALS: A GENDERED MODEL
C Carter
Emory University, Atlanta, GA, USA
Email address for correspondence: [email protected]
Keywords: narratives, illness experience, gender
Background: Narratives of illness, disability, mental disorders, genetic disorders, chronic conditions, dying and death play a key role in shaping our understanding of the human condition. In the past decades efforts have been made to better understand these anthropological illness narratives, with an increasing interest on chronic illness. This research project is a cross-sectional anthropological study of the illness experience of men and women with ALS. ALS presents a particular set of challenges for the construction of an illness narrative, since it has no known etiology, no treatment, and no cure. A critical medical anthropological approach is used to examine the limits and challenges of biomedicine through the lived experience of men and women with a visible and life-limiting chronic illness.
Objectives: The research objectives were: 1) determine how health behaviors (with regard to terminal illness) vary between genders 2) identify the impact of gender on the attitudes of men and women with ALS related to family, emotional support, identity, and explanatory models 3) understand how individuals cope with an illness such as ALS with no known etiology, no treatment and no cure.
Methods: The study used nine participants, five men and four women living in Georgia. Qualitative and quantitative methods were used to collect data, including: semi-structured interviews, structured questionnaire including psychosocial instruments to assess coping style, and participant observation of support group meetings
Results: Results identified both gendered and universal themes among individuals with ALS, and reflect various coping measures and health behaviors that emerge for men and women with ALS.
Discussion: The narratives of female persons with ALS showed the following themes: a longing for aesthetic beauty/feminine qualities, maternal concern/compassion, spousal anxiety, and acceptance. Male ALS narratives uniquely dealt with an acute awareness of diagnosis date, lack of familial provision/protection, dependability, weight and body image, sexual performance and physical activity. Illness narratives provide clinicians and researchers insight about ALS and improve quality of life for patients and their families.
P214 KINSHIP DIFFERENCES IN CAREGIVER BURDEN
F Tramonti1,2
P Bongioanni1,2
I Puppi1
R Leotta1
B Rossi1
xNeurorehabilitation Unit, Neuroscience Department, Azienda Ospedaliero,Universitaria Pisana, Pisa, Italy
yNeuroCare Onlus, Pisa, Italy
Email address for correspondence: [email protected]
Keywords: caregiver burden index, caregiver burden, kinship
Background: Caregiver burden in Amyotrophic Lateral Sclerosis (ALS) is arousing an increasing attention, since the psychosocial demands posed by such a disease are remarkable. In this regard, further investigation is needed to identify differences in burden among specific caregiver subgroups. In our study we evaluated caregiver burden in relation to kinship, with the aim of verifying if different relationships and roles within the family might be related to different burden perceptions.
Patients and methods: We have administered the Caregiver Burden Inventory (CBI) to 72 caregivers (mean age ± SD: 53.4 ± 11.5 yrs; 24 M; 48 F) of ALS patients, and differences related to sex and kinship have been explored comparing subgroups by t-test.
Results: Scores of physical and social burden are significantly higher (p < 0.05) in the general female subgroup. Partners show higher rates (p < 0.05) of physical burden and higher total scores (p < 0.01) than sons and daughters. Among adult children caregivers, daughters complain higher developmental (p < 0.05) and general burden (p < 0.05) than sons.
Discussion: Data analysis suggests significant differences in caregiver burden according to sex/gender and type of relationship with the patient. The most representative subgroup of caregivers is that of partners (especially wives): in such a subgroup caregiver burden seems to be higher. Moreover, differences within the general sample, as well as in the subgroups, support the concept of a higher burden in females.