P149 AN I113T MUTATION IN THE SOD-1 GENE ASSOCIATED WITH SEVERE FRONTOTEMPORAL DEMENTIA IN A PATIENT WITH FAMILIAL ALS
KATZ J, KATZBERG H, WOOLLEY-LEVINE S
California Pacific Medical Center, San Francisco, CA, United States
E-mail address for correspondence: [email protected]
Keywords: SOD-1 mutation, frontotemporal dementia, primary progressive aphesia
Background: Mutations that cause amyotrophic lateral sclerosis/frontotemporal dementia have been found in genes for microtubular associated protein tau-2 (MAPT-2), progranulin (PRG), the valosin containing protein gene (VCP) and in the dynactin 1 gene (DCTN1). While SOD-1 is the most common form of familial ALS, there is little evidence that this mutation can also cause dementia. To date, there have been only two cases of FTD reported with SOD-1 mutation. SOD-1 the mutation was G41S and in the other leu144phe. Neuropsychological testing and PET studies have also been found to show abnormalities in some patients with SOD-1 mutations who do not have frank dementia.
Objective: To present a patient with an I113T mutation in the SOD-1 gene, who developed progressive and ultimately severe FTD two years before the onset of motor weakness and ALS.
Methods: A 54 year old man developed progressive difficulty with language and behavior. The family thought his behavior had become withdrawn. Gradually, he also began to have progressive difficulty with grammar and word finding and became more disinhibited in his behavior. Two years after onset he began to develop weakness. At the time of presentation to our center, three years after onset, he was essentially mute and had difficulty following even one step commands. He could write simple letters but not words and perseverated in responding to commands. He had bilateral hand and ankle weakness. Reflexes were brisk in all four limbs. There was no obvious involvement of bulbar function, with no tongue involvement, suggesting his speech difficulty was purely the result of aphasia.
Family history was significant for ALS in his father, paternal uncle and two of his cousins. His father, who had died years earlier, was thought to have unusual behavioral changes during the last few years of his life, where he was reported as wearing outlandish outfits and drinking excessively for the first time in his life.
Results: Genetic testing revealed an I113T mutation in the SOD-1 gene.
Conclusions: The I113T mutation is the most common SOD-1 mutation in some European countries, but has not yet been associated with dementia. Our case provides further evidence that a variety of SOD-1 mutations can be associated with classic FTD, albeit with very low penetrance compared to the motor phenotype. While this is a single family, the finding is important because it offers insight into the causative mechanisms and relationship between the two diseases.
P150 EYE MOVEMENT PROFILE IN MOTOR NEURONE DISEASE
DONAGHY C1, PINNOCK R2, ABRAHAMS S3, CARDWELL C4, HARDIMAN O5, PATTERSON V1, MCGIVERN RC2, GIBSON JM1
1Department of Neurology, Royal Victoria Hospital, Belfast, United Kingdom, 2Northern Ireland Regional Medical Physics Agency, Royal Victoria Hospital, Belfast, United Kingdom, 3Department of Psychology, University of Edinburgh, Edinburgh, United Kingdom, 4School of Medicine and Dentistry, Queens University, Belfast, United Kingdom, 5Department of Neurology, Beaumont Hospital, Dublin, Republic of Ireland
E-mail address for correspondence: [email protected]
Keywords: Ocular fixation, Saccades, Smooth pursuit
Objective: Studies of eye movements in Motor Neurone Disease (MND) to date have been conflicting and studies have been small. In addition, ocular fixation has not yet been formally examined. With the recent characterization of ocular fixation using saccadic intrusion (SI) amplitude and fixation periods, we performed a cross-sectional observational study to examine ocular fixation, saccades and pursuit eye movements in patients with MND.
Methods: Forty-four patients and forty-five controls were recruited. Ocular fixation, reflexive saccades, antisaccades and smooth pursuit were examined using infra-red oculography. All subjects then underwent a neuropsychological evaluation.
Results: SI amplitude (p = 0.01), antisaccade latency (p = 0.01) and antisaccade type 1 errors (p = 0.03, p = 0.04) were increased and smooth pursuit gain was reduced (p = 0.00) in patients compared to controls. SI amplitude, antisaccade errors and smooth pursuit gain correlated with neuropsychological measures sensitive to lesions of the frontal lobes.
Conclusions: These results indicate that abnormalities in ocular fixation, saccades and smooth pursuit may be a marker of the sub-clinical frontal lobe dysfunction in MND. A longitudinal study to examine if these measurements deteriorate with time would be of great interest as this could provide a quantifiable objective marker of disease progression.
P151 CHANGES IN BEHAVIOUR AND SOCIAL COGNITION IN AMYOTROPIC LATERAL SCLEROSIS WITHOUT DEMENTIA
MEIER S1, TIPPETT L1, CHARLESTON A2
1University of Auckland, Auckland, 2Auckland
E-mail address for correspondence: [email protected]
Keywords: cogniton, abherrant-behaviour, orbitomedial-prefrontal-cortex
Background: Executive dysfunction, associated with dysfunction of dorsolateral prefrontal cortex (DLPFC), has been demonstrated in up to 60% of individuals with ALS. Reports of personality and behavioural changes affecting daily life, in combination with evidence of pathological alterations, suggest functions of the orbital and medial prefrontal cortex (OMPFC) may also be impaired early in the disease course.
Objective: To assess social cognition and behavioural change in individuals with ALS without dementia, using neuropsychological tests known to be sensitive to OMPFC dysfunction.
Methods: Participants comprised of 16 non-demented ALS patients, 16 informants (spouse or family member) and 16 controls matched for age, education, ethnicity and gender. Forced vital capacity (FVC) and disability measured by the ALSFRS-R were recorded for patients; anxiety and depression were assessed by the Hospital Anxiety and Depression Scale. OMPFC function was assessed via a theory of mind task (Faux Pas Test), recognition of emotional prosody (Aprosodia Battery subtest), decision making (Apartment Task), response to changes in environmental reinforcement (Probabilistic Reversal Learning), and behavioural change (NPI administered to informants). DLPFC function was assessed in the areas of cognitive flexibility (oral and written letter and category fluency), planning (Stockings of Cambridge, SOC) and self and informant report of executive functioning (BRIEF-A). Analyses were completed using the Students t-test, repeated measures ANOVA, the Mann-Whitney U test and z-scores.
Results: There were no significant differences between groups for age, years of education, gender, anxiety or depression. On tasks sensitive to OMPFC dysfunction, the ALS group had significantly lower scores on the Aprosodia subtest and the Faux Pas Test, but not the Apartment or Reversal Learning tasks. Aberrant behaviours on the NPI for the ALS group were agitation, apathy, disinhibition, stereotypic behaviour, sleep disturbance and irritability. On tasks sensitive to DLPFC function, the ALS group had significantly lower scores for oral fluency (letter W), mean correct solutions for SOC easy trials (but not hard trials) and time to correct solution for SOC hard trials (but not easy trials). Significant differences were also found between ALS self and informant BRIEF-A group scores for the planning/organisation and organisation of materials subscales and the meta-cognition index, and between ALS self and control BRIEF-A group subscale scores for organisation of materials and the meta-cognition index. In both cases the ALS group rated their performance as better. Individually, 61% of the ALS group had impaired OMPFC function, 46% had impaired DLPFC function, and 31% had no impairment (based on z-scores < -2 or scores outside control range).
Conclusions: OMPFC dysfunction was demonstrated in ALS with group and/or individual impairments in emotional prosody recognition, Theory of Mind, decision making, reversal learning and presence of aberrant behaviours. Individual analysis indicated deficits associated with OMPFC dysfunction are at least as common as DLPFC dysfunction. Due to the particular stresses put on carers and family members by the type of impairments related to dysfunction of OMPFC, we believe detection of such difficulties should be an important clinical priority.
P152 EXECUTIVE DYSFUNCTION IN AMYOTROPHIC LATERAL SCLEROSIS
STOJKOVIC T, STEFANOVA E, STEVIC Z
Institute of Neurology, School of Medicine, University of Belgrade, Serbia
E-mail address for correspondence: [email protected]
Keywords: ALS, cognitive impairment, executive dysfunction
Background: Neuropsychological investigations of amyotrophic lateral sclerosis (ALS) patients have revealed cognitive impairment in some non demented patients, characterised mostly by executive dysfunction. The most striking and consistent deficits were found using tests of verbal fluency.
Objectives: To investigate the profile of executive dysfunction in non-demented patients with ALS.
Methods: Forty two non demented patients with SALS (23 females, 19 males) with probable or definite ALS according to El Escorial criteria were included in this study. Control group comprised of 18 age matched healthy controls. The duration of disease since onset of symptoms, was 18 months. The battery of neuropsychological tests, designed to accommodate the range of physical disability present in ALS, included: Mini Mental State Test; Hamilton Rating Scale for Depression; Scale of Apathy; Test Raven Progressive Matrix; Letter Fluency Test; Category Fluency Test (Animal Naming Test); Boston Naming Test and Cambridge Neuropsychological Test Automated Battery (CANTAB), including: Motor Screening, Spatial Span, Spatial Work Memory and Stockings of Cambridge.
Results: Significant difference between two groups was found on Hamilton Rating Scale for Depression (p < 0.01). Behavioural changes, in the form of apathy, were revealed (p < 0.01). Also, significant difference was found on Mini Mental State Test, as a sign of cognitive impairment (p < 0.01). The most striking impairments were found on tests of verbal fluency- Letter Fluency Test (p < 0.01), Category Fluency Test (Animal Naming Test) (p < 0.01), indicating executive dysfunction on Boston Naming Test (p < 0.01), as a sign of frontal lobe dysfunction. The differences between groups, found on tests of Spatial Work Memory (strategy score) (p < 0.05), and Stockings of Cambridge ((initial thinking time) (p < 0.01) indicate deficits in planning, attention and working memory.
Conclusion: Behavioural changes in the form of apathy, and selective cognitive impairment mostly in the form of verbal fluency deficits, indicates that executive dysfunction is present in ALS patients.
P153 THE FRONTAL ASSESSMENT BATTERY IN ALS.
OSKARSSON B, QUAN D, ROLLINS Y, NEVILLE H, RINGEL S, ARCINIEGAS D
University of Colorado Denver, Denver, CO, United States
E-mail address for correspondence: [email protected]
Keywords: Cognition, executive function, metric
Background: Many persons with ALS suffer from clinically important cognitive impairments. Executive function, a domain of higher-level cognitive processing served by the frontal lobes, is the cognitive domain most affected.
A diagnostically-sensitive and time-efficient method of identifying cognitive impairment among persons with ALS is needed. The Mini-Mental State Examination (MMSE) is the most widely-used brief assessment of cognitive function; however the MMSE contains few items on which performance reflects executive function.
The Frontal Assessment Battery (FAB) was designed as a practical assessment of executive function. Dubois et al. derived the FAB's six items from well-accepted assessments of frontal lobe function. They demonstrated that the FAB was more sensitive to executive dysfunction than the MMSE, that FAB and MMSE performance were not correlated, and that performance on the FAB varied as a function of the severity of frontal lobe disease.
The FAB is brief (5–10 minutes) and is easily learned by all clinicians. Additionally, normative data for age and education is available.
Objectives: To determine if the FAB is well suited for use as a ‘bedside’ screening assessment of executive function among persons with ALS, and if the FAB is a better measure of cognitive dysfunction in ALS than the MMSE.
Methods: We recruited 18 subjects who were not clinically demented for a pilot trial at the University of Colorado. Their mean ALS-FRS was 35 (range 22 to 45). All subjects underwent FAB and MMSE testing. Two patients were excluded from the analysis; one due to being unable to perform several of the tasks on the MMSE and the FAB, and one due to missing data.
Raw MMSE and raw FAB scores were Z-transformed and normalized using normative databases for age and education. A Z-score of ≤ -2 defined impairment on the MMSE and FAB.
Results: FAB score mean was 15.1 (±1.93) out of 18, and the MMSE mean was 29.0 (± 0.894) out of 30. The FAB detected impairment in half (8/16) of the subjects as defined by FAB Z-scores ≤ -2. The MMSE did not detect any abnormalities, none had MMSE Z-scores ≤ -2. The mean FAB Z-score was -2.14(± 2.26), which is lower than the mean MMSE Z-score of 0.108 (± 0.819), p = 0.024. Analyses of unadjusted scores revealed the same pattern of results. FAB scores were not significantly correlated with MMSE scores.
Discussion: This preliminary experience with the FAB suggests that the test will work well as a screening test for cognitive impairment for the majority of persons with ALS. MMSE is a poor measure with which to screen for the presence of executive dysfunction. Further testing comparing the FAB to a “gold standard” battery of neuropsychological tests and other proposed bed side screening tests is warranted.
P154 THE ALS COGNITIVE BEHAVIORAL SCREEN (ALS CBS™): PHASE II VALIDATION
WOOLLEY S1, YORK M2, STRUTT A2, SCHULZ P2, KATZ J1
1Forbes Norris MDA/ALS Research Center, San Francisco, CA, United States, 2Baylor College of Medicine, Houston, TX, United States
E-mail address for correspondence: [email protected]
Keywords: Cognition, Screening, Behavior
Background: Screening for cognitive and behavioural impairments is important in clinical settings when time and resources for detailed testing are limited, or when collecting longitudinal data to demonstrate change is needed. The ALS Cognitive Behavioral Screen (ALS-CBS™) is an assessment tool, developed in our center, containing a compilation of tasks and questions sensitive to frontal lobe dysfunction. The cognitive portion consists of 5 domains specific to frontal lobe function, while the behavioral portion consists of 15 caregiver-directed questions assessing change since disease onset. The ALS-CBS is a 5-minute screen completed in a routine clinical setting by members of the care team.
Objectives: Report current data on the ongoing validation of the revised version of the ALS-CBS™.
Methods: Previous validation resulted in several modifications to enhance accuracy. The current form of the ALS-CBS™ was administered to 40 consecutive ALS patients at two multidisciplinary centers. Patients underwent direct testing by a staff member for the cognitive score, while the behavioral portion was simultaneously completed by the caregiver. Screens were reviewed by the lead neuropsychologists for accuracy and consistency. Descriptive statistics were run to evaluate distribution of scores and correlation with disease-related variables.
Results: The average age of patients (N = 40) at the time of testing was 58 years and mean education was 15 years. Mean FVC (N = 20) was 68% and mean ALS-FRS-R (N = 20) was 32/48. On average, patients were tested 38 months from the time of first symptom. The mean cognitive score among all ALS patients was 15.5 (3.5) (total possible score: 20) versus 18.3 (1.0) in controls. ALS patients who met Neary Criteria for FTD had a mean cognitive score 0/20. Behaviourally, caregivers reported an average score of 33 (8) out of a total of 42 points, reflecting mild changes in behaviour in non-demented ALS patients. The ALS-FTD group had significantly lower behavioural scores (mean: 11). FVC and cognitive scores were not correlated, and there was a mild correlation (r = 0.23) between the cognitive score and ALSFRS-R.
Discussions and Conclusions: Our data provide evidence supporting the utility of a standardized, brief assessment tool for recognizing cognitive and behavioural impairment in the clinical setting. Continued development and validation of the ALS-CBS is currently underway. Six multidisciplinary ALS centers are involved in data collection for this measure, and additional data from these centers will be evaluated in the near future. The goal of this validation is to provide normative data to maximize interpretation of scores, including validation against the gold standard (neuropsychological test battery) and comparison to a larger cohort of normals.
P155 ASSESSMENT OF DEPRESSION IN ALS: A COMPARISON BETWEEN A PHYSICAL-RELATED AND A PSYCHOLOGICAL-RELATED SCALE
CALVO A, VIGNOLA A, GUZZO A, CAVALLO E, PESSIA A, GIACONE S, ELDAN I, CHIÒ A
Department of Neuroscience, Torino, Italy
E-mail address for correspondence: [email protected]
Keywords: Depression, physical symptoms, psychological symptoms
Background: Previous studies showed that the frequency of overt depression in ALS includes patients is relatively low (18 to 30%). However, it is still unclear whether the scales used to assess depression in ALS: some scales include items about physical consequences of depression as “I have crying spells or feel like it” or “ I notice that I'm losing weight” that are normal consequences of ALS physical impairment. These items may seriously spoil the results of depression in ALS patients.
Aims: The aims of this study were: (a) to compare two different depression scales, one related to physical consequences of depression and one focused only on psychological aspects of depression; (b) to correlate these scales to patients physical status; and (c) to find any correlations between depression, anxiety, and quality of life.
Methods: 78 consecutive ALS patients were interviewed. Zung depression scale (ZDS), Hospital anxiety and depression scale (HADS), McGill quality of life questionnaire (MQOL) were administered. Correlations were assessed with Pearson's correlation (p < 0.05), comparison between means was evaluated with student t-test (p < 0.05). Patients’ physical status was evaluated with ALS-FRS.
Results: Patients mean age was 62.1 (SD 11.8); their mean number of years of formal education were 9.5 (SD 4.5), 42 were men (53.8%). Mean anxiety (HADS) score was 7.2 (SD 7.2 range 1–14), mean depression (HADS) score was 5.6 (SD 3.4 range 1–14), mean ZDS score was 40.1 (SD 8.8 range 20–80), mean MQOL score was 7.2 (SD 1.2), mean ALS-FRS score was 28.9 (SD 8.1). Correlation between depression assessed with ZDS and HADS was significant (p = 0.0001); there was also a significant correlation between anxiety and depression (p = 0.0001) and between quality of life and anxiety (p= 0.000), or depression (p = 0.006).
Conclusions: The significant correlation between ZDS score and HADS score suggests that, despite the presence of several items related to physical impairment in the former scale, the two scales for depression give similar results in ALS. A strong relationship between depression and anxiety was found: patients who had a strong negative reaction to the illness showed both anxiety and depression.
P156 ALEXITHYMIA IN ALS-A NEUROPSYCHOLOGICAL APPROACH
ROY-BELLINA S1, BRUNEL H2, ALMOHSEN C2, GÉLY-NARGEOT MC2, CARTON S2, CAMU W1
1Clinique du Motoneurone, CHU de Montpellier, France, 2Université Paul Valéry UFRV Département de Psychologie, Montpellier III, France
E-mail address for correspondence: [email protected]
Keywords: Alexithymia, Neuropsychology, Psychopathology
Background: Depression and anxiety in amyotrophic lateral sclerosis are not that frequent. Patients usually seem to accept the diagnosis without distress. It is of interest to study interactions between the psychology of emotions and the amyotrophic lateral sclerosis patient's cognitive processes.
Objectives: We studied the relationships between alexithymia, characterized by an incapacity to express emotions, and the cognitive perturbations observed in amyotrophic lateral sclerosis. The aim of this research was to answer two questions: 1) are amyotrophic lateral sclerosis patients alexithymic? 2) are the cognitive perturbations observed in amyotrophic lateral sclerosis responsible for alexithymia?
Methods: There were 14 ALS patients, 11 men and 3 women, aged 47 to 81 yrs, mean = 64.43 (±9.33), ALS since 45 months (±36), mean ALSFRS score 39.8/48 and 9 control subjects, 2 men and 7 woman, aged 50 to 79 yrs, mean = 61.89 (±9.1). They answered to the following questionnaires and tests: Toronto's Alexithymia scale at 20 items (TAS 20), Beck's depression scale (BDI II), Apathy scale (Robert et al., 2002) and a battery of executive function (Stroop, Verbal Fluency, Trail Making Test, Empans and Clock).
Results: Reach statistical significance was observed on the Stroop Test (p=.0024) and verbal fluency for both naming form (p = 0.004) and category (p = 0.0012). The TAS 20 score was higher (p = 0.0198) in ALS patients. There was one positive correlation between depression and alexithymia (p = 0.0214).
Discussion and Conclusion : ALS patients are alexithymic and present slight cognitif deficits, but slight cognitif deficits and alexithymia are not correlated. ALS patients present a difficulty to stand their selective attention in inhibition tasks, a lack of research strategies in memory and a bad capacity of lexical initiation.
Therefore, it is possible to considere alexithymia in ALS patients like a defensive and adaptative process, to cope with anxiety, stress and the reality of death.
P157 CONTROLLING FOR VEGETATIVE SYMPTOMS IN THE ASSESSMENT OF DEPRESSION: IS MOOD RELATED TO DISEASE SEVERITY IN ALS?
FINNEMORE T, WOOLLEY S
Forbes Norris MDA/ALS Research Center, San Francisco, CA, United States
E-mail address for correspondence: [email protected]
Keywords: Depression, Assessment, Vegetative
Background: There is substantive current research on depression in ALS but little is known about the relationship between mood symptoms (i.e. sadness, hopelessness) or the evaluative symptoms (i.e. self-criticism, guilt or shame) of depression and disease severity once vegetative symptoms are controlled for. Vegetative symptoms of depression (i.e. fatigue, sleep disturbance) may confound the diagnosis of depression in ALS patients. The Chicago-Multiscale Depression Inventory is a novel measure that has not been used in the ALS population. This measure, developed specifically for use with medical patients, may be useful given its construct of controlling for the vegetative symptoms of depression.
Objectives: To examine the relationship between the mood symptoms of depression and the severity of disease process in ALS while controlling for vegetative symptoms.
Methods: Fifteen subjects with ALS, ages 33–78, volunteered to participate in an imaging study. Subjects completed the Chicago Multi-scale Depression Inventory (CMDI) and the Beck Depression Inventory (2nd ed.) (BDI-II) as part of a larger neuropsychological battery. The CMDI provides standardized scores for subscales of mood, evaluative, and vegetative symptoms, as well as a total score. Patients received neurological examinations including forced vital capacity testing (FVC) and the ALS Functional Rating Scale-revised (ALSFRS-R). Correlations were completed using Pearson's r correlation analyses.
Results: The prevalence of clinically significant mood symptoms of depression was 27%, as measured by either the Mood subscale or the Evaluative subscale of the CMDI. A strong correlation existed between the CMDI Mood subscale and disease severity as measured by the ALSFRS-R (r = − 0.55) and FVC (r = − 0.45). Mood symptoms were weakly correlated with disease duration (r = 0.168). The Vegetative subscale of the CMDI was not significantly correlated with FVC or ALSFRS-R and was modestly correlated with duration of symptoms (r = − 0.37). The Evaluative subscale of the CMDI was highly correlated with ALSFRS-R (r = − 0.58), and FVC (r = − 0.75) but weakly correlated with symptom duration (r = 0.26) and the Vegetative subscale (r = 0.29).
Discussion and Conclusions: These results suggest that the mood and evaluative symptoms of depression in this sample were associated with severity of disease process as measured by ALSFRS-R and FVC, but not related to disease duration. The finding that the vegetative symptoms of depression were weakly correlated with disease process might suggest denial or lack of insight into motor-related physical disability. The results of this study suggest the need to focus on evaluative symptoms of depression in relation to disease progression in future research.
P158 A STUDY ON COGNITIVE FUNCTION IN MOTOR NEURON DISEASE
GAO F1, SHEN Y1, WANG H2, ZHANG Y1, YANG Q1, ZHANG N1, FAN D1, ZHANG J1
1Department of Neurology, Peking University Third Hospital, Beijing, China, 2Department of Psychiatry, Peking University Sixth Hospital, Beijing, China
E-mail address for correspondence: [email protected]
Keywords: cognitive impairment, frototemporal dementia, neuropsychiatry inventory
Objectives: To investigate the frequency of cognitive impairment and frontotemporal dysfunction in motor neuron disease (MND).
Methods: One hundred cases of MND patients during December 2006 to October 2007, underwent mini mental state examination (MMSE) for cognitive survey and neuropsychiatry inventory (NPI) for neuropsychological survey, meanwhile Hamilton depression scale (HAMD) and Hamilton anxiety scale (HAMA) for mood statement. Demographics, site of onset and ALS-FRS were also investigated.
Results: Of the 100 patients (60 male and 40 female, age range from 24 to 78 years, mean 51.99±11.41 years), 45 were diagnosed as definite ALS, 29 as probable ALS, 16 as possible ALS, and 10 as lower motor neuron syndrome (LMNS). Eighty-two had limb onset and 18 bulbar onset. Sixty-one patients had bulbar dysfunction. The course of disease was 4–94 months, confirmed diagnosis for 0–47 months. Only depression state and ALS-FRS were of statistical difference between MMSE normal and abnormal. MMSE indicated that 24.2% (23/95) of all patients had mild cognitive impairment. 15.8% (15/95) of all patients were abnormal in both MMSE and NPI. Depression presented most often in all the NPI subitems. Apathy, agitation, euphoria, aberrant motor behavior were proved to be of great clinical value to frototemporal dysfunction in the present study, 10 patients (10%) presented at least 1 of the 4 subitems. Since patients with anxiety and depression would also act as abnormal in NPI, we took a follow up after 3 months with anti-depression therapy. Two patients did not improve. Their psychomotor dysfunction initially emerged and lasted for more than 6 months, indicating that they may have frontotemporal dysfunction.
Conclusions: MND patients’ cognitive function were relatively reserved. 1/4 of the 100 patients have mild cognitive impairment. A part of the patients were psychomotor abnormal, in the follow-up, 2 patients may have frontotemporal dysfunction, with potential to become frototemporal dementia.
P159 A POPULATION BASED SURVEY OF COGNITIVE DECLINE IN ALS
PHUKAN J, GALLAGHER L, CORR B, PENDER N, HARDIMAN O
Beaumont Hospital, Dublin, Ireland
E-mail address for correspondence: [email protected]
Keywords: cognitive, FTLD, population
Background: Up to 60% of the ALS patients attending specialist clinics are reported to have mild cognitive decline and a proportion of these may progress to develop frontotemporal dementia. However, the population-based frequency and natural history of cognitive decline in ALS remains to be established.
Objective: To determine the frequency and natural history of cognitive decline in ALS in a defined population-based cohort.
Design and Methods: All Incident patients in the Republic of Ireland are identified through the Irish ALS Register. Each patient is assessed in their own home, provides a detailed family history and undergoes a full neurological examination and validated neuropsychological evaluation, modified to control for slower motor speed and speech difficulties. Progression is determined by three separate evaluations at 6-month intervals.
Results: 70 incident patients have been identified over an 18 month period. 51 patients and matched controls have participated in a detailed neuropsychological assessment to date. 13 patients have bulbar-onset disease and 17 have a family history of neurodegenerative disease. Cluster analysis based on executive function was performed to generate 2 groups: impairment (n = 23) and no impairment (n = 28). ALS patients demonstrated performance below control means on several measures of executive function and memory. Patient mean z-scores indicate verbal memory and behaviour change were more prominent in those with evidence of executive impairment. Those with executive impairment had significantly greater change in executive dysfunction and apathy (as per Frontal Systems Behaviour Scale). Apathy was the most marked behavioural change in both groups. Other cognitive processes such as naming were intact.
6 patients met consensus criteria for frontotemporal lobar dementia: 3 for behavioural variant FTD, 1 for non-fluent progressive aphasia, and another for semantic dementia. Cognitive impairment did not correlate with ALS severity. Kindreds of ALS patients with cognitive impairment had a higher frequency of other neurodegenerative disease.
Conclusion and Relevance: There is a high prevalence of cognitive impairment (primarily affecting executive function and memory) and behavioural change in ALS. However preliminary data suggests that the population based frequency of cognitive impairment is lower than that reported from clinic based studies. This study supports the conjecture that ALS is part of a continuum of neurodegenerative disease.
P160 PREVALENCE AND SEVERITY OF DEPRESSION IN MOTOR NEURONE DISEASE (MND) AND OTHER MOTOR DISORDERS
TAYLOR LJ, WICKS P, LEIGH PN, GOLDSTEIN LH
Institute of Psychiatry, London, United Kingdom
E-mail address for correspondence: [email protected]
Keywords: Severity, Prevalence, Depression
Background: The prevalence of depression in Motor Neurone Disease (MND) is portrayed in the research literature as being surprisingly low. This impression has been reinforced by reports that the prevalence of depression is lower in MND than in several other neurological conditions. The disorders (such as Parkinson's disease, Multiple Sclerosis) to which prevalence rates of depression in MND have been compared are characterised by additional neuroanatomical, cognitive and behavioural features that have been reported to exacerbate depression. These additional confounds render comparisons of prevalence rates of depression between MND and these conditions less helpful and the conclusions drawn from such comparisons in need of review.
Objective: The current study sought to examine whether the prevalence in depression is uniquely low by comparing the severity and prevalence of depression in patients with MND to that in patients with other neurological motor disorders that have a similar physical disability profile to MND.
Method: The Beck Depression Inventory (revised) (BDI-II), the Major Depression Inventory (MDI), Hospital Depression and Anxiety Scale (HADS) and the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised were sent to 225 patients from a tertiary referral Motor Nerve Clinic in London, UK.
Results: Data were obtained collected from 109 patients: 63 with MND and 46 with other neurological motor disorders. After covarying for potentially confounding demographic and functional ability variables, ANCOVAs revealed no significant effect of patient group on total scores on the BDI-II, MDI or the HADS depression subscale. The prevalence of depression did not differ significantly between patient groups according to classifications from the BDI-II, HADS depression subscale and the MDI.
Discussions and Conclusions: The current findings contradict the impression that patients with MND have a surprisingly low prevalence of depression. Patients with similar disability profiles to MND did not significantly differ from MND patients with regard to both severity of depressive symptoms and prevalence of depression on the BDI-II, HADS or the MDI. The conclusions have significant implications for our understanding of the psychological impact of MND and suggest that the impression of a generally low prevalence of depression in MND patients is revised. Given the negative impact of depression on quality of life and the potential impact of mood on both patients’ acceptance of life-prolonging measures and prognosis, the possibility of depression in people with MND should be given due consideration.
P161 ALS PATIENTS WANT TO BE TOLD MORE ABOUT COGNITIVE CHANGE
WICKS P, FROST J
PatientsLikeMe, Cambridge, Mass, United States
E-mail address for correspondence: [email protected]
Keywords: Cognition, information seeking, neuropsychology
Background: Once thought to impact only voluntary motor function, ALS/MND is now seen as a multi-system disorder in which a minority of patients experience mild cognitive dysfunction or frontotemporal dementia. Despite clinical guidelines advocating supplying complete information to patients, educational materials on ALS often state that the mind is unaffected.
Objectives: We sought to establish how much patients and caregivers understand about ALS, what they have been told to expect by their physician, and if they would have appreciated more complete information.
Methods: A two-part survey was administered online. An “ALS quiz” gauged participants’ knowledge of physical and psychological aspects of ALS. A second questionnaire assessed which symptoms patients had discussed with their clinician and explored patients’ desire to receive information on psychological effects.
Results: 247 ALS patients and 87 caregivers participated. Participants knew less about psychological symptoms than physical ones (72% correct responses versus 82%; paired t(333)=-5.04, p < 0.001). Patients commonly reported being told by their doctor about physical symptoms such as problems walking (85%) or stiffness/cramps (74%) but not psychological issues like emotional lability (46%) or cognitive change (11%). The majority of patients (62%) and carers (71%) indicated a desire to be informed that cognitive change or dementia might occur.
Discussion: Although we as healthcare professionals know that cognitive change can and does occur in ALS, we are not telling patients. It is incumbent upon as a profession to find the best way and the most appropriate time to tell patients what could happen, so that if cognition does become an issue, they are prepared for it. We could learn from the experiences of colleagues in Parkinson's disease and Multiple Sclerosis for guidance.