Executive Dysfunction and
Language Impairment in
Frontotemporal Dementia
Sandra Hogsed, MS, CCC-SLP
Western Carolina University
November 9, 2010
What is Frontotemporal
Dementia?
“Frontotemporal dementia (FTD), or referred to as
frontotemporal lobar degeneration (FTD), is a group of related
conditions resulting from the progressive degeneration of the
temporal and frontal lobes of the brain. These areas of the
brain play a significant role in decision-making, behavioral
control, emotion and language.”
Frontotemporal Dementia, University of California, San Francisco, Memory and Aging Center,
http://memory.ucsf.edu/ftd/.
Disease Onset
 FTD usually first appears when someone is in their mid-40s
to early-60s and causes a steady, gradual decline in the
ability to complete the daily activities of life. The disease can
last anywhere from three to 17 years from the first symptom
until death, with an average duration of eight years after
diagnosis. FTD occurs equally in men and women. In a small
percentage of cases it is inherited.
 The Association for Frontotemporal Dementias,
 http://www.ftd-picks.org/
Prevalence
 FTD represents an estimated 10%-20% of all dementia cases
and is recognized as one of the most common dementias
affecting a younger population. It is estimated that FTD affects
approximately 250,000 Americans.
The Association for Frontotemporal Dementias,
http://www.ftd-picks.org/
Normal Brain vs.
FTD
Image retrieved on 9/19/10 from http://www.riversideonline.com
Types of FTD
The term "frontotemporal dementia" (FTD) includes several
different clinical subtypes:
1)
2)
3)
4)
Behavioral variant FTD- "frontal variant FTD" or "pick's
disease"
Semantic dementia- “temporal variant FTD”
Progressive non-fluent aphasia
FTD with motor neuron disease, which includes corticobasal
degeneration, progressive supranuclear palsy and motor
neuron disease.
The specific areas of the brain affected by each subtype cause
different symptoms.
Frontotemporal Dementia, University of California, San Francisco, Memory and Aging Center,
http://memory.ucsf.edu/ftd/.
Behavioral Variant FTD Symptoms
 Behavioral and personality
changes
 Decreased concern for social
norms
 Disinhibition and loss of personal
control
 Lack of insight into their own
 Withdrawal and apathy
 Increased appetite for sweets
 Personal hygiene deterioration
 Hypersexual behavior
 Compulsiveness,
perseverations or stereotyped
repetitive acts
behaviors, denial of deficits
 Lack of responsibilities
Bozeat, S., Gregory, C., Lambon, R., & Hodges, J. (2000). Which neuropsychiatric features distinguish frontal and
temporal variants of frontotemporal dementia from Alzheimer’s disease? Journal of Neurology, Neurosurgery,
and Psychiatry, 69, 178-186.
Hodges, J. & Miller, B. (2001). Classification, genetics and neuropathology of frontotemporal dementia. Introduction
to the special topics papers, part 1 (Review) Neurocase, 7, 31-35.
Neary, D., Snowden, J., Gustafson, L., Passant, U., Stuss, D., Black, S., Freedman, M., et al. (1998). Frontotemporal
lobar degeneration: a consensus on clinical diagnostic criteria. Neurology, 51, 1546-1554.
Semantic Dementia
 Word-finding difficulties
 Fluent aphasia
 Anomia
 Impaired comprehension of word meaning
 Inability to match semantically-related pictures or objects
As the disease progresses, behavioral and personality changes similar to
the behavioral variant FTD may become apparent.
The Association for Frontotemporal Dementias,
http://www.ftd-picks.org/
Progressive Non-Fluent Aphasia
 Hesitant, effortful speech
 Relatively preserved comprehension of speech
 Relatively preserved reading and writing abilities
 Increased difficulty with production of speech related to
weakness and incoordination
 Speech that sounds imprecise and uncoordinated
 Difficulty with swallowing
The Association for Frontotemporal Dementias,
http://www.ftd-picks.org/
Motor Neuron Disease
 Muscle weakness, which can involve the arms, legs, face, tongue or neck
 Clumsiness, or difficulty with fine motor movements of the hands
 Tripping or falling due to weak or stiff legs
 Shortness of breath due to weak muscles in the diaphragm
 Muscle atrophy
 Fasciculations
 Muscle cramps
 Dysphagia
 Dysarthria
 Spasticity
 Hyperreflexia- exaggerated reflexes
 Uncontrollable outbursts of laughing or crying
The Association for Frontotemporal Dementias,
http://www.ftd-picks.org/
To summarize…what cognitive
domains are affected by FTD?

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Receptive Language
Memory and Learning
Thinking
Expressive Language
Attention
Executive Functioning and Reasoning
Caregivers of FTD
 http://www.youtube.com/watch?v
=dP4PoUkVy0U
Videos about
FTD
Frontotemporal Dementia (Mayo
Clinic)
 http://youtu.be/EHSdNjhkvE8
 Does the young person with
behavior variant FTD remind you
of another disorder?
What causes this
debilitating disease?
Pathology of FTD
Pathology occurs with degeneration and gliosis. This begins in the
orbitofrontal cortex of the brain.
 Degeneration results in abnormally folded protein “clumps.” One type of
inclusion is called the Pick body, named for the neurologist who first
described this disease, Arnold Pick.
 Gliosis develops in the damaged region.
The posterior part of the brain is spared in FTD, so many day-to-day
functions are normal in the early stages.
Rosen, H., Hartikanen, K., Jaqust, W., Kramer, J., Reed, B., Cummings, J., Boone, K., Ellis, W.,
Miller, C., Miller, B. (2002). Utility of clinical criteria in differentiating frontotemporal lobar
degeneration (FTD) from AD. Neurology, 58, 1585-1586.
Tauopathy
At least two different disease proteins are implicated in FTD pathology.
These include tau and TDP-43.
FTD-Tau
 The protein tau is found to be
responsible in the disease
process, such as when it
accumulates as aggregates in
Pick’s disease, corticobasal
degeneration and progressive
supranuclear palsy.
FTD -TDP
 A proteinopathy that results
when abnormal TDP-43
protein accumulates in nerve
cells.
Yoshiyama, Y., Lee, V., Trojanowski, J. (2001) Frontotemporal dementia and tauopathy.
Current Neurology and Neuroscience Reports, 1, 413-421.
Genetics
 A subset of patients with FTD-TAU and FTD-TDP have a
family history and genetic mutations have been identified.
These inherited cases of FTD-TAU are associated with
mutations in the tau gene where as FTD-TDP cases may be
associated with abnormalities of the progranulin gene or the
TDP-43 gene.
Geser, F., Martinez-Lage, M., Kwong, L., Lee, V., Trojanowski, J. (2009) Amyotrophic lateral sclerosis,
frontotemporal dementia and beyond: the TDP-43 diseases. Journal of Neurology, 256:1205–1214.
Murray, B., Lynch, T., Farrell, M. (2005) Clinicopathological features of the tauopathies. Biochemical
Society Transaction, 33, 4.
Tauopathy
Image retrieved on 9/19/2010 from http://ellisonfoundation.org
Brain Location and Symptoms
Behavioral (Frontal)
 Orbitofrontal lobe dysfunction- early
personality change and disinhibition
 Medial frontal (anterior cingulate)apathy, abulia, mutism, apraxia,
perseveration
 Dorsolateral frontal lobedisorganization and sequential
organization
 Non-dominant anterior temporal
lobe-selfishness/callousness,
antisocial traits, lack of empathy, new
artistic or musical talent
Murray et al., (2005)
Aphasic (Temporal)
 Dominant posterior temporal or
inferior frontal lobe- halting,
agrammatic speech with frequent
paraphasic errors but relatively
preserved comprehension
 Temporal- semantic dementiaimpaired comprehension and wordfinding deficits
FTD Progression
“As FTD progresses, the various subtypes merge so that
patients develop combinations of clinical syndromes and
eventually progress to a global dementia.”
Murray, et al., (2005)
Subtypes of FTD eventually merge
Murray, et al. (2005) Image retrieved on 11/05/10 from
http://www.biochemsoctrans.org
Journal Article #1
Torralva, T., Roca, M., Gleichgerrcht, E. , Bekinschtein, T., and
Manes, F. (2009) A neuropsychological battery to detect
specific executive and social cognitive impairments in
early frontotemporal dementia, Brain, 132; 1299-1309.
Question?
 Traditional cognitive tests may not be sensitive to the early
identification of bvFTD. This study aimed to identify specific
neuropsychological tests that were particularly sensitive to
identification of the specific executive and social cognitive
deficits in those with early bvFTD.
Torralva, et al. (2009)
Classical Cognitive Measures
 Wisconsin Card Sorting Test
 Verbal fluency tests, or the Trail Making Test
These may fail to detect the dysexecutive syndrome shown by
these early bvFTD patients in everyday life (Gregory et al.,
1999, 2002).
New Criteria for Diagnosis
 There has been a recent revision of diagnostic and research
criteria for bvFTD. Deficits in executive and social cognition
tasks are now considered a core feature in its entirety.
 The presence and detection of executive and social
dysfunction may be particularly useful for diagnosis during
the early stages of the disease.
Kipps and Hodges (2006)
Rascovsky, et al. (2007).
Hodges, (2007)
 Although severe deficits in various aspects of social cognition
(i.e. Theory of Mind) and complex decision-making tend to
appear in early stages of bvFTD, these domains are not often
part of the assessment.
Gregory et al., (2002);
Torralva et al., (2007).
Purpose
 This study attempted to enhance the traditional cognitive
assessment battery with the addition of more comprehensive
tests of complex executive social functioning to increase
sensitivity for the detection of executive and social cognitive
impairment in patients with early bvFTD.
New Proposed Battery
Tests that measure performance of “daily life” activities within a “real
life” environment; combined with traditional cognitive tests to increase
sensitivity for the detection of executive and social cognitive
impairment in patients with early bvFTD.
 Multiple Errands Test (Burgess, 2002)
 Hotel Task (Manly et al., 2002)
 complex decision making (Iowa Gambling Task) (Bechara et al.,
1994)
 social cognition (Theory of Mind tests) (Baron-Cohen, 1997;
Stone et al., 1998).
Methods
 35 bvFTD patients with early/mild stages of the disease, fulfilled
Lund and Manchester criteria for bvFTD diagnosis (Neary et al.,
1998).
 Dementia severity was assessed using the Clinical Dementia
Severity Rating Scale (CDR) (Hughes et al., 1982).
 All patients underwent a standard examination battery including
neurological, neuropsychiatric and neuropsychological
examinations and a MRI-SPECT.
 All patients showed frontal atrophy on MRI, and frontal
hypoperfusion on SPECT, when available.
 Only patients with frontal lobe atrophy were included in this
study although the current diagnostic criteria does not specify
need.
General Neuropsychological Battery
 Addenbrooke’s Cognitive Examination (ACE) and the Mini Mental State
Exam (MMSE; Folstein et al., 1975).
 Premorbid IQ - Buenos Aires Word Accentuation Test (WAT-BA; Burin et
al., 2000).
 Attention and concentration- forward digit span task (Wechsler, 1991) and
the Trail Making Test Part A (TMT-A; Partington and Leiter, 1949).
 Memory- logical memory subtest from the Wechsler Memory ScaleRevised (Wechsler, 1991).
 Language comprehension- adapted version of the Token Test (Spreen and
Benton, 1977).
 Naming assessed with the adapted version of the Boston Naming Test
(Kaplan et al., 1983).
Proposed Executive and Social
Cognition Battery (ESCB)
 The Frontal Assessment Battery test (FAB; Dubois et al., 2000).
 Backward digit span (Wechsler, 1991)
 Letters and Numbers (Wechsler, 1939)
 Word Fluency Tests
 Trail Making Tests Part B (Partington, 1949)
 Modified Wisconsin Card Sorting Test (Nelson, 1976)
 Executive and social cognition battery (ESCB)
 Multiple Errands Test Hospital Version (Shallice and Burgess,
1991)
 The Hotel Task (Manly et al., 2002)
 Iowa Gambling task (Bechara et al., 1994)
 The Mind in the Eyes Test (Baron-Cohen et al., 1997)
 Faux Pas Test (Stone et al., 1998).
Results
 16 participants with scores above 86 (hiACE)
 19 participants with a score of 86 or below (loACE).
 By classifying bvFTD as being either above (hiACE) or below (loACE) the cut-off
score of the Addenbrooke’s Cognitive Examination (ACE), the researchers were able
to show that the hiACE group performed significantly below the healthy controls on
the tests of the battery proposed, but did not differ on most of the standard (or
classical) tests
 Performance on every classical executive test included in the battery was
significantly different for loACE compared to the control (CTR)
Statistical Analysis
Participants clustered into 3 groups for statistical analysis
 Healthy controls
 bvFTD with an ACE score higher than 86 points
 bvFTD with an ACE score of 86 points or less
The score of 86 points (out of 100) was used, because it is
accepted as the cut-off value of the ACE in diagnosing
dementia (Mathuranath, et al., 2000).
Summary
 Testing incorporated tasks that would resemble real-life demands,
decision-making processes or social situations.
 As expected the loACE group differed from healthy control on all
measures of the ESCB. The hiACE group differed from controls in
measures of real-life planning and organization, complex decisionmaking and theory of mind tests. This group made more errors than
healthy controls (inefficiencies), acted more impulsively (rule breaks),
with no apparent planning, and poor organization of the tasks (task
failures).
“This study demonstrated that traditional measures of frontal
executive function may be ineffective in the early detection of
subtle executive and social cognition deficits in bvFTD.
Patients with an apparent high performance on a standard
neuropsychological test do not differ significantly from controls
in their performance on basic cognitive domains or classical
tests of executive function.”
Torralva, et al. (2009)
Limitations
 Diagnosis of bvFTD was based on clinical assessment alone
and not on pathological analysis.
 This study only tested specificity of global score in
discriminating bvFTD from normal controls.
Journal Article #2
 Pakhamov, S., Smith, G., Chacon, D., Feliciano, Y., Radford,
N., Caselli, R., Knopman, D. (2010) Computerized
analysis of speech and language to identify
psycholinguistic correlates of frontotemporal lobar
degeneration, Cognitive and Behavioral Neurology, 23,
3, 165-177.
Question?
 The purpose of this research was to evaluate the
use of a semiautomated computerized system for
measuring speech and language characteristics in
patients with frontotemporal degeneration (FTD).
 The need for improved definition of syndromes and
phenotypes is a key theme in dementia research in general,
and frontotemporal lobar degeneration (FTD) in particular.
Currently, FTD comprises 3 syndromes:
 Behavioral variant (bvFTD)
 Progressive nonfluent aphasia
 Semantic dementia
The inclusion of progressive logopenic aphasia (PLA) as
either a variant of FTD or Alzheimer is currently being debated.
Objective
 Careful clinical evaluation is critical to FTD diagnosis,
particularly in the early stages of disease progression.
 A systematic analysis of spontaneous speech samples is
considered “the single most valuable aspect of the diagnosis”
for the aphasic FTD syndromes (Rohrer, et al.,2008).
 Research in aphasia has contributed a set of instruments in the
form of picture description tasks designed to elicit and rate
spontaneous speech, including the Boston Diagnostic Aphasia
Examination Cookie Theft stimulus.
Drawback of Traditional Measures?
 Traditionally carried out manually.
 The problem with this is the results are subjective and may not
have the detail and precision to pick up on subtle nuances.
 Detailed measurements of syntax, semantics, and prosody—
the 3 areas identified in a survey of clinicians’ views on the
clinical usefulness of aphasia test batteries.
Beele, et. al, (1984).
Objective and Precise Instruments
 Advances in computerized natural language processing (NLP)
and automatic speech recognition (ASR) are making it possible
to develop objective and precise instruments for automated or
semiautomated analysis of speech and language.
Hosom, J. Shriberg, L., & Green, J. (2004). Diagnostic assessment of childhood apraxia of speech using
automatic speech recognition (ASR) methods. Journal of Medical Speech Language Pathology, 12,
167-171.
Roark, B., Hosom, J., Mitchell, M., & Kaye, J. (2007). Automatically derived spoken language
markers for detecting Mild Cognitive Impairment. Paper presented at the International
Conference on Technology and Aging (ICTA).
Speech and Language
Characteristics in Frontotemporal
Lobar Degeneration
 Progressive nonfluent aphasia- dysfluent, effortful,
agrammatical speech.
 Semantic dementia- nonverbal and verbal naming and
recognition deficits with relatively preserved grammar.
Despite these differences, there is considerable overlap
between their language specific manifestations.
Language related deficits of bvFTD
 In bvFTD, the language related deficits tend to be observed
at the higher discourse level, rather than syntax, phonology,
and semantics found with the other FTD variants.
 Patients with bvFTD show impaired working memory that
manifests itself through deficits in sentence comprehension
(Cooke, et al., 2003), thematic role processing in verbs
(Peele, et al.,2007; Murray, et al., 2007), and altered
discourse characteristics (Ash, et al., 2006): discourse
coherence, cohesion, and “empty” speech (overuse of
pronouns) (Almor, et al.,2001; Almor, et al., 2001; Glosser, et
al., 1991).
Problems in Current Diagnostic
Techniques
 Thompson et al (1997) suggested that neuropsychologic
tests may be too narrow to capture the richness of the
behavioral and cognitive features of FTD and even obscure
the differences between patient groups.
Proposal
 Qualitative assessments of error types were proposed to
complement neuropsycologic test scores in obtaining a more
complete characterization of FTD variants. This research was
designed in hopes that computerized linguistics and NLP
technology may help to quantify some of these qualitative
measures.
Methods
 38 patients diagnosed with 1 of 3 FTD syndromes and PLA
were recruited from 3 academic medical centers.
 All 38 participants underwent neuropsychologic testing that
included the Boston Diagnostic Aphasia Examination Cookie
Theft Picture Description Task.
Diagnostic Criteria
 Only patients with behavioral variant frontotemporal dementia
(bvFTD), progressive non-fluent aphasia (PNFA), progressive
logopenic aphasia (PLA), and semantic dementia (SD) were
included in the study –based on Neary criteria (Neary et al.,
1998).
 All patients were required to have imaging studies showing
focal cerebral atrophy of at least 1 of these: the anterior
temporal lobes, frontal lobes, insula, or caudate nuclei.
Criteria for diagnosis of the FTD
disorders
 PNFA- diagnosed by expressive deficits of at least 3 of these:
nonfluency, speech hesitancy or labored speech, word
finding difficulty.
 PLA- diagnosed with fluent aphasia with anomia but intact
word meaning and object recognition.
 SD- diagnosed with loss of comprehension of word meaning,
object identity, or face identity.
 bvFTD- diagnosed with personality and behavioral changes
significant enough to interfere with work or interpersonal
relationships, and at least 5 core symptoms of the disease.
Cognitive Instruments
All participants were administered a standard
neuropsychologic test battery consisting of these tests:

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California Verbal Learning Test Free Recall
Number Cancellation
Digits Backward from Wechsler Memory Scale-Revised
Stroop Test
Digit-Symbol Substitution
Verbal Fluency for Letters and Categories
Boston Naming Test
All tests were scored by board certified behavioral neurologists.
Tests were chosen based on Knopman et al., 2008.
Computerized Psycholinguistic
Assessments
 natural language processing (NLP) and automatic speech
recognition (ASR)—a set of computational techniques used for
computerized analysis of speech and language.
The use of ASR and NLP to psychometric testing is new; however
it was felt by the researchers of this study to be a natural
extension of the capabilities of this technology. For this study, a
system for semiautomated language and speech analysis based
on NLP and ASR technology. The system was configured for this
study to process audio recordings of speech elicited during the
Cookie-Theft picture description task of the Boston Diagnostic
Aphasia Examination. Audio input was manually transcribed and
then aligned with the transcribed text. (Refer to Appendix A of the
study).
The computerized analysis enables precise measurement and
quantification of durational and frequency characteristics of the input
at the level of utterances (2 or more coarticulated words), words, and
individual phonemes. The following variables were defined using this
system:
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Pause-to-word ratio
Fundamental frequency variance
Part-of -speech perplexity
Word-Level perplexity
Pronoun-to-noun ratio
Word count
Total duration of speech in the sample
Mean prosodic phrase length
Correct Information Unit count
Normalized long pause count (silent pauses > 400ms in duration)
Normalized filled pause count
Normalized silent pause count (silent pauses >150 ms in duration)
Normalized false start count
Normalized repetition count
Normalized dysfluent even count (filled pauses, false starts, and repetitions)
Refer to Appendix B in the article for definitions of these variables and technical details
Results
 After 38 samples were examined using the semiautomatic
psycholinguistic variables, 4 components were identified as
accounting for 71% of the total variance in all variables:
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speech length
hesitancy
empty content
grammaticality
Discriminating between FTD Variants
 Of all tests evaluated in this study, only 2 showed statistically
significant differences in means:
 Verbal category fluency
 Correctness on the Boston Naming Test
Mean Scores
Verbal Category Fluency
 bvFTD
 PNFA
 PLA
 SD
12.87
11.90
7.75
5.33
Boston Naming
 bvFTD
 PNFA
 PLA
 SD
23.20
23.40
16.75
5.0
Note the significant differences between bvFTD and SD on both tests
Semiautomated Psycholinguistic
Measures
Measures obtained from all 38 study participants showed
significant differences in:
 pause-to-word ratio (P < 0.01)
 normalized dysfluent event count (P < 0.001)
 ratio of pronouns to nouns (P = 0.01)
This demonstrates increased differences between PNFA and
all 3 other groups- bvFTD (P < 0.001), PLA (P = 0.01) and SD
(P = 0.02). The PNFA group demonstrated increased use of
nouns and verbs vs. the other groups.
Discussion
 This computerized approach to quantifying language appears
to have removed the subjectivity inherent in manual
assessments, and may improve the reliability and
comparability of measurements across different studies.
 This semiautomated approach offers a viable alternative
between computerized and manual testing based on
spontaneous speech and should allow examination of syntax,
semantics, and prosody.
Key Points
 Speech hesitancy, characterized by ratio of silent pauses to
words and the ratio of dysfluent events to words are sensitive
indicators of PNFA.
 Verbal category fluency and correctness on the Boston
Naming Test and pronoun-to-noun ratio and pause-to- word
ratio showed significant differences between the 4 FTD
groups.
 Category fluency and confrontation naming are among the
first single-word measures to be affected in patients with
PNFA.
 Pronoun-to-noun ratio was the highest in subjects with the
SD variant and lowest in the PNFA variant.
Key Points (Cont.)
 The Boston Naming Test and category fluency may be more
sensitive to semantic deficits and are likely to be useful in the
diagnosis of SD and anomia. However, both of the tests fail
to distinguish between the behavioral and the nonfluent
aphasia variants of FTD.
 Computerized measurements of pause-to-word ratio indicate
that the PNFA variant has nominally the highest proportion of
pauses and dysfluent events including filled pauses, false
starts, and repetitions. This may complement verbal category
fluency and the Boston Naming tests in distinguishing
between the 4 FTD variants.
Key Points (Cont.)
 Pronoun-to-noun ratio:
 highest in SD-associated with impaired naming
 lowest in PNFA-associated with impaired speech
production, but not necessarily picture naming.
• Differential diagnosis of the different FTD subtypes are quite
favorable for the emergence of specific treatments for the
tauopathies that are associated with PNFA and the TDP-43
proteinopathy associated with semantic dementia.
• Automated speech analysis could not replace clinicians but
offers a standardized way of characterizing expressive
speech and could serve as a means of classifying subjects
for a clinical trial and by either supporting or calling into
question a clinical diagnosis.
Limitations and Future
Directions
 Sample size is relatively small.
 FTD is relatively rare which limits sample size.
 The semiautomated approach to language and speech
analysis resulted in some loss of precision in time alignments
and part-of-speech identification.
 Limitations in available technology with regards to complexity
of ability to analyze speech.
Treatment
 “There is no known treatment that can stop or reverse FTD.
There are some researchers now testing promising
medications. Certain caretaking techniques, lifestyle changes
and various medications can reduce the symptoms and
improve the quality of life for people affected by FTD.”
Frontotemporal Dementia, University of California, San
Francisco, Memory and Aging Center,
http://memory.ucsf.edu/ftd/.
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