32
Cognitive and Psychological Assessment and Support
21st International Symposium on ALS/MND
SESSION 8B COGNITIVE AND PSYCHOLOGICAL
ASSESSMENT AND SUPPORT
C46 SOCIAL COGNITION IN ALS: IMPAIRED
COGNITIVE AND AFFECTIVE THEORY OF MIND
VAN DER HULST E-J, BAK TH, ABRAHAMS S
University of Edinburgh, Edinburgh, United Kingdom
C47 THE NATURE OF LANGUAGE DEFICITS IN
ALS: SEMANTIC IMPAIRMENTS IN ACTION
SEQUENCING
VAN DER HULST E-J, ABRAHAMS S, BAK TH
E-mail address for correspondence: s.abrahams@ed.ac.uk
University of Edinburgh, Human Cognitive Neuroscience, Edinburgh, United Kingdom
Keywords: social
dysfunction
E-mail address for correspondence: dina.jozefa@ed.ac.uk
cognition,
cognitive
change,
prefrontal
Background: A key component of Social Cognition is Theory of Mind (ToM) conceptualized as the ability to ascribe
mental states to others. The Eye Gaze Test (EGT) is a classical ToM test and assesses an individual’s ability to judge the
preference of another by using the direction of their eye gaze
as a cue. This process is fundamental for appropriate social
interaction. Deficits on this test have been found in both ALS
and FTD. ToM has been fractionated into cognitive and affective components, involving the recognition of the thoughts
and feelings of another respectively. Disruption of affective
ToM has been related to damage to the ventromedial prefrontal cortex, a region implicated early in FTD but which has
not been as yet identified as typically affected in ALS.
Objectives: This study examined whether ALS patients display changes in both cognitive and affective ToM. Furthermore, the influence of attentional factors were explored.
Methods: Sixteen patients with ALS (non-demented) and 16
healthy participants, matched for age, sex and years of education, completed the cognitive and affective EGT. The EGT
comprised of three features: type of judgement (cognitive,
affective or physical control), attention (presence or absence
of a distracter) and complexity of judgement (first or second
order ToM). In addition, each participant was administered
two tests of visual processing.
Results: The analyses revealed that ALS patients were significantly impaired in both cognitive and affective ToM trials.
ALS patients displayed significantly lower scores for first order
cognitive (P 0.01) and affective judgements (P 0.005) as
well as second order cognitive judgements (P 0.05) with a
trend for second order affective judgements (P0.067). The
patients were not impaired on physical control judgements or
visual processing. Moreover there was no effect of having a
distracter present.
Discussion and conclusions: Cognitive and affective components of ToM appear to be affected in some non-demented
ALS patients who show difficulties in recognizing the thoughts
and feelings of another. This deficit indicates involvement of
the ventromedial prefrontal cortex and suggests that the prefrontal involvement in ALS may be extensive in those who do
not show overt dementia. This selective deficit was found in
patients with intact visual processing abilities. Moreover there
was no effect of distracter present indicating that this was not
the result of an attentional dysfunction. Hence this deficit
reflects a basic social cognition impairment. These results
could account for some of the behavioural abnormalities
observed in ALS and implies that some ALS patients may
have difficulties in primary interactions with carers.
Keywords: neuropsychology, language, embodied cognition
Background: A subset of patients with ALS show subtle difficulties in a range of cognitive functions, including language.
In particular, recent research has uncovered deficits in action
processing in ALS-patients both with and without dementia,
although the exact nature of these deficits remains to be elucidated. Findings from these studies have been interpreted as
support in favour of the influential theory of embodied cognition, which states that both motor functions and knowledge
of actions are dependent on the same underlying neural networks.
Objectives: This study investigated the nature of linguistic
and conceptual deficits in patients with classical ALS. In particular, it explored the distinction between two types of relationship between actions: parallel (actions of a similar
character, eg typing - writing) and sequential (actions, which
usually follow each other, eg peeling - cutting).
Methods: Twenty-one ALS-patients and 17 healthy controls
(HCs), matched for age, education and sex, were compared
on a neuropsychological battery of tests. The patients had to
choose the correct answer from an array of two different
choices. The battery comprised of language tests: semantic
association for Objects and Actions (O and A) and Action
Sequencing (AS). Furthermore, a relatively difficult test of
Audio Visual Information Processing (AVIP) was added as a
measure of complex non-semantic information processing.
Both reaction times (RTs) and error rates were recorded.
Results: Analyses revealed that ALS-patients made significantly more errors than HCs on AS (P 0.021), while both
groups displayed an equal amount of errors on O and A
(Ps0.067). In terms of the reaction times, taking out the
possible influence of motor slowing, basic motor speeds were
subtracted in all three conditions, yielding cognitive decision
times. Results showed a main effect of group (P 0.016).
Although ALS-patients exhibited longer cognitive decision
times than HCs overall, patients were not slowed on any of
the individual tests in particular (P 0.158). There were no
differences in reaction times and errors between patients and
controls on AVIP (Ps0.233).
Discussions and conclusions: Our study detected a specific
deficit in the task requiring the comprehension of action
sequencing in a group of non-demented ALS-patients. In contrast, no deficits were observed on action and object association tests as well as in audiovisual information processing. The
deficits in action sequencing were confined to the accuracy of
responses only and did not appear to influence cognitive decision times. Our findings suggest that action deficits observed
in ALS patients might in fact be due to a sequencing deficit.
Moreover, they raise the question whether sequencing deficits
Platform Communications
are specific to language or possibly extend to other neuropsychological domains, constituting one of the basic cognitive
deficits in ALS.
Cognitive and Psychological Assessment and Support
33
C49 DIAGNOSTIC VALIDITY OF THE ALS
COGNITIVE BEHAVIORAL SCREEN
RUSH B1, WOOLLEY SC2, BOYLAN K1
1Mayo
Clinic, Jacksonville, FL, United States, 2California
Pacific Medical Center, San Francisco, CA, United States
C48 PREFRONTAL LOBAR DETECTING: A
MORE SENSITIVE BATTERY FOR SCREENING
COGNITIVE IMPAIRMENT IN EARLY-PHASE ALS?
E-mail address for correspondence: rush.beth@mayo.edu
JI Y1, WEI L2, DENG M1, WANG K2, FAN D1
Keywords: cognitive screen, cognitive impairment, diagnostic
validity
1Peking
University Third Hospital, Beijing, China, 2 Anhui
Medical University First Hospital, Hefei, China
E-mail address for correspondence: dsfan@yahoo.cn
Keywords: prefrontal lobar dysfunction, prospective memory,
early phase
Background: ALS is now considered as a multisystem disease with co-occurrence of frontotemporal syndrome. Imaging studies show the prefrontal lobe is the most involved area
in ALS patients with behavioral and cognitive impairment.
Objective: The aim of this study is to find a screening battery
to detect subtle cognitive deficits in ALS patients at early
stage.
Methods: Eighty consecutive patients diagnosed as ALS
according to the El Escorial criteria and 59 normal controls
were matched for sex, age and education. Both groups were
assessed with a series of neuropsychological tests state as follows: the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI), Frontal Behavior Inventory
(FBI), verbal fluency test (VFT), Stroop Color Word Interference Test (CWT), and prospective memory (PM) including
event-based prospective memory (EBPM) and time-based
prospective memory (TBPM). To further explore the topic a
subset of patients underwent further examination involving
picture and music emotional perception, theory of mind or
decision making (Iowa Gambling Task and risk-taking task).
Results: As previous studies reported, our patients also did
not differ from normal controls on MMSE, but significantly
differed on behavioral inventories including NPI (4.604.78
vs 0.160.59, P0.001) and FBI (3.193.59 vs 0.180.54,
P0.001). However, we found our patients did not differ from
normal controls in traditional neuropsychological tests on
executive function including VFT and CWT. On the other
hand, statistically significant differences were found between
ALS patients and the normal controls on the prospective
memory (EBPM: 5.552.20 vs 6.371.80, P0.043; TBPM:
4.851.51 vs 5.651.10, P0.001), faux pas task
(23.1310.09 vs 28.916.20, P0.002) and the arousal of
negative pictures (6.381.32 vs 7.181.12, P0.008). More
interestingly, we found TBPM is more sensitive than EBPM
in early phase patients (possible and probable-laboratory supported ALS). We did not find differences between ALS patients
and normal controls on the valence and recognition of pictures, music emotional perception, Iowa Gambling Task and
risk-taking task.
Conclusions: Prefrontal lobar dysfunction does exist among
ALS patients, and may be spread from medial to lateral part.
Behavioral test, PM and theory of mind used in this study is
more sensitive in detecting behavioral and cognitive impairment in ALS patients at early stage than the classical cognitive
measures.
Background: Cognitive and behavioral symptoms of amyotrophic lateral sclerosis (ALS) are increasingly recognized.
The ALS Cognitive Behavioral Screen (ALS-CBS) (1–2) is a
20 point screening measure with unclear diagnostic validity.
Objectives: To compare diagnostic classifications of cognitive
impairment from the ALS-CBS to those from gold standard
neuropsychological evaluation.
Methods: Retrospective review of 24 cases of ALS referred
for evaluation of cognitive and behavioral symptoms between
January 1, 2008 and March 31, 2010. Each participant was
administered the ALS-CBS and a standard of care neuropsychological evaluation and received two diagnoses; one from the
ALS-CBS and one from neuropsychological evaluation. The
following diagnoses were considered: ALS, ALS with cognitive
impairment/no dementia (ALS-ci), ALS with behavioral
impairment/no dementia (ALS-bi), or ALS with frontal-temporal dementia (ALS-FTD). A score of 11 on the cognitive
form of the ALS-CBS suggested cognitive impairment and a
score 5 suggested ALS-FTD. Diagnostic classifications from
the ALS-CBS and the neuropsychological evaluation were
compared and diagnostic validity was determined.
Results: Ten out of the 24 cases were female (42%), with a
median age of 68 years (range: 43 - 83 years), median education of 14 years (range: 9 - 20 years), and median of 18
months (range: 6 - 55 months) duration between motor neuron disease symptom onset to cognitive evaluation. Fifty percent of cases had bulbar-onset disease. Neuropsychological
evaluation confirmed cognitive impairment in 16 out of 24
cases (67% base rate; 9 ALS-FTD and 7 ALS-ci). There were
50% bulbar cases in the cognitively impaired and unimpaired
groups. Using a cut-off score of 11 on the ALS-CBS, 46%
cases (11/24) had cognitive impairment (8 ALS-FTD, 3 ALSci). This cut-off score yielded a sensitivity of 69% and a specificity of 100%. Of the 5 cases for which the ALS-CBS
yielded a false negative diagnosis of cognitive impairment, 4
of the cases had a diagnosis of ALS-ci and 1 case had a diagnosis of ALS-FTD on neuropsychological evaluation.
Conclusion: The ALS-CBS demonstrates excellent specificity using a cut-off score of 11 for determining cognitive
impairment. The ALS-CBS may have limited sensitivity to
ALS-ci or cognitive impairment without dementia.
Discussion: Data support the validity of the ALS-CBS as a
screen for cognitive impairment in ALS. The cut-off score of
11 on the cognitive form of the ALS-CBS is empirically
justified particularly when ALS-FTD is present. Alternate
cut-off scores or language screening items could improve the
sensitivity of the ALS-CBS to ALS-ci when it is present.
References:
1. Woolley SC. Third International Research Workshop on Frontotemporal Dementia in ALS. London, Ontario, Canada, 2009.
2. Woolley SC, et al. Amyotrophic Lateral Sclerosis. In
Press.
34
Cognitive and Psychological Assessment and Support
C50 LONGITUDINAL COGNITIVE SCREENING
USING THE ALS COGNITIVE BEHAVIORAL
SCREEN (ALS-CBS™)
WOOLLEY SC1, MOORE DH1, VALAN M1, SPITALNY M2,
KUSHNER G1, FORSHEW DA1, MILLER R1, KATZ J1
21st International Symposium on ALS/MND
C51 COMPUTERIZED FRONTAL ASSESSMENT
OF AMYOTROPHIC LATERAL SCLEROSIS
POLETTI B, LAFRONZA A, SOLCA F, TICOZZI N,
MORELLI C, MESSINA S, SILANI V
1California
Pacific Medical Center, San Francisco, CA, United
States, 2Research Computing, Mill Valley, CA, United States
Department of Neurology and Laboratory of Neuroscience, ‘Dino
Ferrari’ Center, University of Milan, IRCCS Istituto Auxologico Italiano, Milan, Italy
E-mail address for correspondence: Woolles@sutterhealth.org
E-mail address for correspondence: poletti.barbara@gmail.com
Keywords: cognition, screening, longitudinal
Keywords: frontal functions, computerized tools, neuropsychological assessment
Background: The ALS Cognitive Behavioral Screen (ALSCBSTM) has been validated as a clinical measure but its utility in research is unknown. Its ease of administration is ideal
for longitudinal assessment of cognition in large cohorts.
Objectives: To evaluate cognitive screening data obtained
from the WALS multi-center trial of lithium carbonate and to
characterize cognitive status of this research cohort over time.
Methods: 109 patients with ALS were enrolled. The maximum cognitive score on the ALS-CBSTM is 20; scores at or
below 10 are suggestive of frontotemporal dementia (1). The
mean score for a clinical cohort (n112) was 14.6 (1). Longitudinal cognitive change was calculated using the difference
in scores over 12 months. Age of onset, duration of symptoms,
forced vital capacity (FVC), ALSFRS-R scores, and fatigue
were measured in the trial.
Results: The mean age of subjects was 56 years, mean ALSFRS-R at study initiation was 37.5, and mean FVC was
94.8%. Ninety-eight subjects completed the ALS-CBSTM longitudinally. The average cognitive score was 16.68 (2.67) at
baseline and the cohort remained stable over 1 year (16.69).
Only 7% of subjects revealed significant cognitive declines
(5 points) but 4% revealed significant increases. Declines in
cognition were not associated with age, symptom duration,
low FVC, low ALSFRS-R scores, fatigue, or drug side
effects.
Discussion: The subjects in this clinical trial did not show
significant decline over a 12-month period. This suggests that
frontal lobe decline is not prominent among patients who
meet inclusion criteria for a clinical trial. The mean cognitive
score in the trial was higher than in a clinical cohort suggesting that patients enrolling in trials are less likely to be impaired
than clinical patients. These results also differ from previous
longitudinal research in a clinical cohort which revealed longitudinal cognitive decline (2).
Conclusion: Clinical trials may enroll patients with different
cognitive profiles than those seen in routine clinic. This may
relate to research patients needing to be motivated, having
limited duration of disease due to inclusion criteria, or having
higher FVC’s which limits those enrolled with significant bulbar involvement. While the methodology does not allow us to
generalize our conclusions, the lack of progression in this
cohort also points towards a relative paucity of cognitive
impairment in this group. The results add to increasing evidence that a screening tool is a practical way to monitor cognition and behavior longitudinally in large cohorts.
References:
1. Woolley SC, York MK, Moore DH, et al. ALS 2010; in
press.
2. Phukan J, Gallagher L, Jordan N, et al. ALS 2009;10(1):43.
Background: The study of cognition and behaviour as a feature of Amyotrophic Lateral Sclerosis (ALS) is an evolving
field still lacking a full consensus on terminology, diagnostic
criteria, and clinical significance of any detected abnormalities. Marked discrepancies remain regarding the incidence of
abnormalities and characteristics of the impairments that
define ALS, frequently depending on the kind of cognitive
tool used. Frontal alterations in ALS have been variously
described and assessed in literature. Moreover, different
degrees of frontal involvement in ALS starting from minimal
frontal changes to overt Fronto-Temporal Dementia (FTD)
have been documented, thus revealing the importance of
detecting the whole spectrum of frontal involvement characterizing motor neurone disease’s cognitive pattern. The terms
ALSci (ALS with cognitive impairment), ALSbi (ALS with
behavioural impairment), and ALS-FTD are developing concepts that aim to capture the key differences between the
various clinical phenotypes. Computerized neuropsychological tools seem to be ideal in exploring and characterizing
frontal cognitive functions.
Objectives: The purpose of this study was to analyze frontal
cognitive functioning of ALS patients with frontal cognitive
computerized measures.
Methods: Fifteen patients fullfilling El Escorial Criteria for ALS
and fifteen controls underwent an extensive neuropsychological
and psychodiagnostic assessment. Patients received the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRSr).
Attentional skills and frontal functioning have been investigated
with a computerized neuropsychological battery named TEA
(Test of Everyday Attention). This battery, focused on attention
and frontal functions, assess the ability of patients to selectively
attend, sustain their attention, divide their attention between two
tasks, switch attention from one task to another, and withhold
(inhibit) verbal or motor responses. Clinical tools for assessing
psychological and emotional status included: MOS 36-Item
Short-Form Health Survey (SF-36), Beck Depression Inventory
(BDI) and State-Trait Anxiety Inventory-Y (STAI-Y).
Results: Our data show quantitative differences in cognitive
performances between patients and controls, with higher difficulties in the more complex attentional tasks for the former
and better scores for the latter. Significant differences of data
emerge on different frontal measures, while a general cognitive
slowness characterized patient’s performances. Patients displayed lower performances on frontal task of cognitive functioning. Subjects differed significantly for the presence of
anxiety symptoms. Neuropsychological and psychological data
were correlated with functional and respiratory parameters.
Discussion and conclusions: Computerized neuropsychological assessment seems an ideal tool in detecting small ‘frontal’ cognitive changes frequently observed in the cognitive
frontal spectrum of ALS. Implications for clinical purposes
will be discussed.