C60 RAPID SCREEN EXAM FOR THE DETECTION OF FRONTAL AND TEMPORAL DYSFUNCTION SYNDROMES: APPLICATION TO ALS
FLAHERTY-CRAIG C, BROTHERS A, DEARMAN B, ESLINGER P, SIMMONS Z
Penn State College of Medicine, Hershey, PA, United States
E-mail address for correspondence: [email protected]
Keywords: Dementia, Cognition, Intervention
Background: The prevalence of frontotemporal dementia (FTD) in the ALS population is estimated to be between 30 to 50 percent. FTD is recognized to present as three distinct subtypes, including isolated behavioural change, a frontal cortical associated aphasia of a progressive non-fluent type and a temporal cortical associated aphasia of a fluent type characterized by loss of semantic knowledge. Given the aggressive course of the disease process, we wanted to identify ALS patients whose emerging FTD was rendering them less capable of independent decision-making. We developed an evaluation approach that included a behavioural inventory as well as screening measures of language change characteristic of either frontal dysfunction (FD) or temporal dysfunction (TD).
Objectives: To develop incidence rates of ALS-FD and ALS-TD. To refine our multifaceted program of patient and family support, in response to the presence of either FD or TD, to keep the affected patient as fully engaged in ongoing treatment decision making as possible, from the time of diagnosis to the terminal stage of the disease process.
Methods: We administered our 20-minute exam to 118 limb-onset and 80 bulbar-onset ALS patients. We evaluated the incidence of acquired change in fluency, abstract reasoning, judgement and behaviour. Assessment included the Neurobehavioral Cognitive Status Examination, letter fluency, category fluency, and the New Adult Reading Test (NART). The NART provided an estimated verbal IQ. Reading was screened by the BDAE Oral Reading and Reading Comprehension-Short Form. Changes in behaviour and personality from a caregiver perspective were assessed by the Frontal Behavioural Inventory (FBI). Oral word list generation was followed by a word list copy task, to control for bulbar effects.
Results: Significant deficiencies were found in the domains of fluency, abstract reasoning, judgment and behaviour in 25.3%, 17%, 29.5% and 2.4% of limb onset and 38.1%, 19.2%, 46.7%, and 4.3% of bulbar-onset patients. Predominant FBI traits included logopenia, apathy, inflexibility, irritability, and verbal apraxia.
Discussion and Conclusions: Among patients with deficiencies, we found a predominance of cognitive frontotemporal dementia and temporal dementia, with only rare instances of isolated behavioural disturbance. The present study bridges the gap in screen evaluation normative studies of FTD in ALS. The sample was large in size, with strong representation of both non-bulbar and bulbar onset subtypes. The measures chosen allowed for detection and differentiation of both frontal and temporal dysfunction syndromes, as well as for the establishment of incidence rates of the three recognized FTD sub-types. The availability of a concise, practical FTD syndrome assessment tool in the multidisciplinary ALS clinic will strengthen a team's ability to recognize and address barriers to communication and decision making in the course of treatment planning, from the time of diagnosis to the terminal stage of the disease process.
C61 NEUROANATOMICAL CORRELATES OF APATHY IN ALS: A 4 TESLA STUDY USING FRACTIONAL ANISOTROPY.
WOOLLEY S1, ZHANG YU2, WEINER M2, KATZ J1
1Forbes Norris MDA/ALS Research Center, San Francisco, 2Center for Imaging of Neurodegenerative Disease, VA Med Center, San Francisco, CA, United States
E-mail address for correspondence: [email protected]
Keywords: Apathy, FTD, Imaging
Background: The association between ALS and frontotemporal dementia (FTD) has led to the study of behavioural abnormalities in ALS to better specify the prevalence of FTD in this population. The most common behavioural abnormality identified in ALS is apathy, although clarification is needed as to whether this reflects a frontally-mediated disorder versus the sequalae of factors such as respiratory compromise, weakness or psychological factors. In FTD studies (non-ALS) using voxel-based morphometry, apathy correlates with right hemisphere dysfunction and anterior cingulate changes. To better clarify whether a frontotemporal disease process may explain behavioural changes in ALS, we examined whether similar correlations exist in the ALS population with regards to apathy.
Objectives: Using a diffusion tensor imaging (DTI) method by measuring fractional anisotropy (FA), we used a voxel-based analysis of whole brain changes to investigate the loss of white matter integrity as it relates to apathy in ALS.
Methods: Eighteen non-demented patients with ALS were enrolled in an imaging study. DTI imaging was accomplished using a 4.0-Tesla (Bruker/Siemens) MRI system, based on EPI sequence (TR/TE = 6000/ 77ms; field of view 256×224cm; 128×112 matrix size, 2 x 2 x3 mm3 resolution; b = 0, and b = 1000 with 6 non-collinear directions). Alignment of FA images from all study subjects was performed by SPM2 software. Correlation between FA and apathy scores was tested voxel-by-voxel using a general linear model accounting for age and gender. Significance level was set at p < 0.005 without multiple comparison. Neuropsychological evaluations were completed; apathy was assessed using the Frontal Systems Behavioral Scale. Patients with dementia or depression were excluded from the analysis.
Results: The mean age of the cohort was 58 years, mean FVC was 91% and mean ALSFRS-R score was 35. FA reduction along bilateral motor, temporal and frontal white matter, which included bilateral uncinate fibers and right anterior cingulate fibers, was significantly correlated with current apathy scores. When premorbid levels of apathy were controlled for, FA reduction was significantly correlated with alterations in bilateral superior frontal white matter and temporal-parietal white matter fibers.
Discussion and Conclusions: These results represent the first known dataset regarding neuroanatomical correlates of behavioural change in non-demented ALS patients. Findings suggest an organic basis for apathy and are consistent with research on apathy in FTD and other dementias. Frontal and temporal white matter damage may be associated with increased apathy, even early in the ALS disease course. Specifically, white matter changes in right hemisphere and anterior cingulate may be associated with apathy, consistent with previous findings in FTD.
C62 SOCIAL AND EMOTIONAL COGNITION AND BEHAVIOUR: EVIDENCE OF SUBCLINICAL FRONTOTEMPORAL DEMENTIA IN ALS
ABRAHAMS S1, GIRARDI A1, NEWTON J2, MACPHERSON S1
1University of Edinburgh, United Kingdom, 2Western General Hospital, Edinburgh, United Kingdom
E-mail address for correspondence: [email protected]
Keywords: Cognition FTD Behaviour
Background: Although an association between ALS and frontotemporal dementia (FTD) has been recognized, the exact nature of the relationship has remained elusive. It is well established that a subgroup of ALS patients suffer from behaviour and cognitive change as found in FTD and a further proportion are thought to display more subtle cognitive change, indicating a continuum of impairment. Evidence in support of the association rests primarily on the repeated demonstration of verbal fluency impairments (a test of executive function sensitive to frontal lobe lesions) in non-demented ALS patients, but deficits on other tests have been less striking. FTD is a heterogeneous disorder and recent research has demonstrated that patients with frontal variant FTD may retain intact performance on standard neuropsychological tests at the early stages of the disease, despite a distinctive behavioural syndrome. Moreover these patients show early dysfunction in social cognition, emotional processing and decision making on experimental measures long before the onset of overt executive dysfunction.
Objectives: These studies investigated whether ALS patients show deficits on a range of experimental tests of social and emotional cognition and corresponding behaviour change similar to that found in the early stages of frontal variant FTD.
Methods: In the first study 19 patients with classical ALS and 20 healthy controls undertook a test of emotional decision making in which choices were made based on reward. Behavioural measures included the Frontal Systems Behaviour Scale and the Manchester Behaviour Interview. In the second study a group of 15 patients with ALS and 21 controls undertook a range of tests of social cognition (including judgement of preference based on eye gaze and reading the mind in the eyes) and tests of emotional cognition (recognition of emotions from facial expressions).
Results: Analysis of the emotional decision making test revealed a deficit in ALS patients, in that although controls learnt to avoid the disadvantageous stimuli through the task, the ALS patients did not. In addition, patients showed corresponding behaviour change (apathy, disinhibition and executive dysfunction) from the onset of the disease, with particular increases in apathy and changes in affect and social behaviour. In the second study, deficits were found on tests of social and emotional cognition. ALS patients were particularly impaired at inferring the mental state of others and in recognising other people's emotions.
Conclusions: These studies demonstrated evidence of deficits in social and emotional cognition and corresponding behaviour change on tests which have been shown to be sensitive to the early stages of frontal variant FTD. The findings indicate evidence of a subclinical syndrome in a significant proportion of ALS patients without overt dementia. The relative contribution of dorsolateral and ventromedial prefrontal pathways to the cognitive and behavioural profile in ALS are discussed.
C63 INFLUENCE OF FRONTOTEMPORAL DEMENTIA ON ALS PATIENTS AND CAREGIVERS QUALITY OF LIFE AND DEPRESSION
VIGNOLA A, PALMARIELLO V, PEDONE V, CALVO A, CAMMAROSANO S, ILARDI A, MOGLIA C, MUTANI R, CHIÒ A
Department of Neuroscience, Torino, Italy
E-mail address for correspondence: [email protected]
Keywords: Frontotemporal dementia, quality of life, caregivers
Background: The frequency of frontotemporal dementia (FTD) in ALS patients ranges from 5 to 50% of cases, according to the methods used to diagnose cognitive deficits. The relationship between frontotemporal dementia and quality of life (QoL) in ALS patients and caregivers also remains unclear
Objective: To evaluate the frequency of frontotemporal dementia in ALS using the Frontal System Behaviour Scale (FrSBE), an instrument that evaluates patients’ behavioural changes from the patient's and caregivers perspective, using three different scales: apathy, disinhibition, and executive functions; to evaluate the relationship between FTD and patients’ and caregivers’ QoL and depression.
Methods: Sixty-three consecutive ALS patients and their primary (unpaid) caregivers were administered the FrSBE, the Zung Depression Scale (ZDS), the McGill QoL Questionnaire (MQOL). Statistical analysis was performed with SPSS 12.0.
Results: Patients’ mean age was 61.7 years (SD 10.3); 50.7% of patients were men. Caregivers mean age was 53.7 years (SD 12.7). Patients mean MQOL score was 6.8 (SD 1.3), ZDS score was 29.2 (SD 6.3); 11 patients (17.4%) were over the depression cut-off. Twenty-four (38.0%) patients showed emotional lability. Caregivers mean MQOL score was 6.7 (SD 1.3), mean ZDS score was 38.6 (SD 7.9). According to FrSCE, caregivers suspected that 39.8% of patients were over the FTD cut-off, while only 20.6% of patients reported a score over the cut-off for FTD. Considering the 3 subscales of the FrSBE, according to the caregivers evaluation no FTD component was prevalent, while patients reported themselves as significantly less disinhibited (p < 0.01) and with less executive deficit (p < 0.01) than caregivers did. Patients self-evaluating themselves over the cut-off for FTD had higher score for depression (p < 0.01) and lower scores for QoL (p < 0.05). Caregivers who reported patients’ score over the cut-off for FTD had a lower QoL (p < 0.01) and higher depression (p < 0.05).
Conclusions: Using the FrSBE, 40% of patients evaluated by their caregivers had a score over the cut-off for FTD. FTD in ALS patients negatively influenced their caregivers’ QoL and depression. Patients who reported a FrSBE score over the cut-off for FTD were more depressed and had a lower QoL than the other patients.
C64 RESEARCH INTO COGNITIVE CHANGE IN ALS/MND: IMPLICATIONS FOR CLINICAL CARE AND MANAGEMENT
GOLDSTEIN L
Institute of Psychiatry, King's College London, United Kingdom
Email address for correspondence: [email protected]
Keywords: cognition, behaviour, care
Research into cognitive change in ALS/MND has progressed considerably and it is now well-accepted that cognitive functions may be compromised in people with ALS/MND. However, a number of differences in approach to measuring and classifying cognitive change in the disease have resulted in conflicting views as to the prevalence of cognitive change and whether or not it may be progressive. In addition, a number of clinical variables may influence cognitive functioning and attention needs to be paid to these in understanding the nature or extent of cognitive change that may be found. New lines of research into cognitive change are also considering alterations in emotional processing in people with ALS/MND. Of related importance, research is being undertaken increasingly into the behavioural as well as cognitive manifestations of the disease process, again with differing approaches being taken to measurement and classification.
In addition to highlighting the profile of cognitive change in MND, the present talk will provide an overview of some of the issues and controversies concerning cognitive (and behavioural) involvement in the disease. Allowing for these, the practical implications of understanding how the potential nature of cognitive change in ALS/MND might be relevant to everyday decision-making and care will be discussed.