Keywords
primary progressive aphasia - assessment - diagnosis - dementia
Learning Outcomes: As a result of this activity, the reader will be able to (1) describe the purposes
of speech–language assessment for individuals with PPA; (2) summarize how a comprehensive
assessment battery (including speech, language, and cognition) can inform diagnostic
decision making in PPA; (3) select appropriate speech–language and cognitive assessments
that can be used to inform diagnosis and treatment for individuals with PPA.
Primary progressive aphasia (PPA) is a disorder marked by a gradual loss of communicative
function caused by neurodegenerative disease affecting speech and language networks
in the brain.[1]
[2] There are three widely recognized clinical variants of PPA, each with a unique signature
of communication deficits and underlying neural changes: the semantic, nonfluent/agrammatic,
and logopenic variants. The last two decades have brought a great deal of progress
in clarifying these clinical phenotypes and their neuropathologic underpinnings and,
increasingly, patients are referred to speech-language pathologists (SLPs) for assessment
and treatment. This paper will focus on approaches to assessment in PPA, the purposes
of which are threefold: (1) to establish the PPA diagnosis and clinical variant, when
possible; (2) to determine appropriate interventions for patients and their families;
and (3) to track progression of deficits over time.
Primary Progressive Aphasia Diagnosis
Primary Progressive Aphasia Diagnosis
Current consensus criteria for PPA diagnosis recommend a two-tiered diagnostic process.[1] First, a PPA diagnosis should be established based on the following general criteria:[1]
[2] the most prominent clinical feature (at onset and for initial stages of disease)
should be communication difficulty and this should be the primary contributor to impaired
activities of daily living; symptoms should not be attributable to other neurological,
psychiatric, or medical disorders; and prominent nonlanguage cognitive or behavioral
impairments should not be present initially.
The second stage of diagnosis involves confirming PPA subtype (semantic variant, nonfluent/agrammatic
variant, or logopenic variant[1]
[3]). It is important to note that not all individuals with PPA can be classified into
one of the established clinical variants.[4]
[5]
[6]
[7]
[8] However, when possible, determination of clinical variant is an important step,
as it may help inform the diagnostic picture as well as the nature and likely progression
of speech–language deficits. Speech–language phenotype, in conjunction with in vivo
biomarkers (e.g., neuroimaging, genetic, and biofluid studies[9]) may assist in predicting disease etiology. Although there is only a probabilistic
association between PPA phenotype and underlying pathology, the semantic and nonfluent/agrammatic
variants are most commonly associated with the frontotemporal degeneration spectrum
of pathologies (most often TDP-43 and tauopathy, respectively) and the logopenic variant
is associated with Alzheimer's pathology in most cases.[10] With the emergence of clinical trials targeting specific pathological processes,
the SLP may play a contributing role in discerning the likelihood of a given underlying
disease based on clinical phenotype. Even more importantly from a rehabilitation standpoint,
determination of clinical variant can help elucidate the linguistic nature of deficits
(semantic, phonological, or grammatical) and strengths, which may guide treatment
planning. Lastly, while there is considerable variability in the rate and nature of
progression from patient to patient, diagnosis by variant may aid the clinical team
in predicting the most likely progression of cognitive, linguistic, and motoric features.[11]
[12]
[13] As such, establishing PPA subtype may inform the medical and rehabilitative plan
of care and help patients and families to prepare for the future.
Current consensus criteria enumerate core and associated speech–language features
that must be present for diagnosis by variant.[1] For a diagnosis of semantic variant, both anomia and single-word comprehension impairment
must be present, as well as three of the following: impaired object knowledge, surface
dyslexia/dysgraphia, spared repetition, and spared grammar/motor speech. For a diagnosis
of nonfluent/agrammatic PPA, at least one of the core features of agrammatism or apraxia
of speech must be present, and two of the following associated features must also
be present: impaired sentence comprehension, spared single-word comprehension, and
spared object knowledge. For a diagnosis of logopenic variant, both core features
of word-finding difficulty and impaired repetition must be present as well as three
of the following: phonological errors in speech, spared single-word comprehension/object
knowledge, spared motor speech, and an absence of agrammatism.
The Evaluation Process
Case History and Interview
As with any standard diagnostic battery performed by a SLP, it is critical that a
thorough case history be obtained from the individual with possible PPA. It is important
to gain information regarding the initial presentation, the emergence of any additional
symptoms with time, and the degree of linguistic versus cognitive or motoric impairment
at the time of assessment. During the interview, clinicians should take note of speech–language
features (e.g., word finding difficulties, agrammatism, phonological errors); nonlinguistic
cognitive deficits that may emerge with time (e.g., episodic memory impairment); atypical
behavioral symptoms that may arise, particularly with semantic variant PPA (e.g.,
disinhibition, apathy, loss of empathy); or motoric symptomatology (e.g., limb apraxia,
parkinsonism, dysphagia) that may develop, most commonly in nonfluent/agrammatic PPA.
Any family history of dementia or other relevant medical diagnoses (especially neurodegenerative
conditions) should be ascertained, if not already noted in the medical record. Impairments
of hearing and/or vision should be documented, as well as the individual's status
as a monolingual, bilingual, or multilingual speaker. Impaired hearing or vision may
need to be addressed before a valid assessment can be performed, and assessment materials
should be linguistically appropriate to the speaker. To inform treatment planning,
the clinician should inquire about current functional communication needs and limitations.
For example, it is important to ascertain the variety of communication settings (work,
home, community settings), partners (family, friends, coworkers), and modes (telephone,
face-to-face, written) that are most relevant in the patient's daily life. It is helpful
to involve the individual's primary communication partner(s), if possible, to ensure
an accurate and complete case history.
Global Assessment of Linguistic Function
In addition to a clinical interview, a thorough speech–language evaluation should
be conducted, which allows for characterization of impaired versus preserved speech–language
abilities. This evaluation also serves to establish a quantitative index of aphasia
severity that can be used as a baseline measure from which to track the progression
of symptoms and document potential treatment gains. Standard aphasia batteries developed
for use with stroke-induced aphasia are commonly used in PPA research centers as well
as typical clinical practice. The Western Aphasia Battery (WAB)—Revised[14] and Boston Diagnostic Aphasia Examination (BDAE)[15] may be used to characterize an individual's overall language profile and to provide
a general measure of aphasia severity. Additionally, the WAB has been shown to be
a useful tool for distinguishing among PPA subtypes.[16]
[17] However, it is likely that aphasia batteries developed for stroke may not be adequately
sensitive to detect the subtle deficits that are observed in early stages of PPA.
Furthermore, using stroke-induced aphasia classification nomenclature (such as Broca's
or Wernicke's) is not appropriate when characterizing PPA.
Assessments Designed for Differential Diagnosis and Tracking Severity in PPA
A recent systematic review identified nine neuropsychological assessments that were
developed or adapted specifically for diagnosis or characterization of PPA.[18] Several of these can be used successfully to differentiate between clinical variants,[19]
[20]
[21]
[22] and two were designed specifically to gauge severity and progression in PPA.[19]
[23] The Sydney Language Battery (SydBat) is a brief battery of tasks (picture naming,
word comprehension, semantic association, and repetition) designed to differentiate
among PPA subtypes.[22] The Repeat and Point Test is a brief measure developed to differentiate between
semantic and nonfluent variants by requiring patients to repeat 10 multisyllabic words
and point to the target among semantic and phonological distractors.[21] Discriminant function analysis revealed that SydBat was able to distinguish among
PPA variants with 80% accuracy, whereas the Repeat and Point Test distinguished semantic
from nonfluent variant cases with 100% accuracy.
The Progressive Aphasia Severity Scale (PASS)[23] is an instrument designed specifically to characterize symptoms and track progression
in PPA. With this instrument, clinicians rate the severity of deficits in speech and
language domains (articulation, fluency, syntax/grammar, word retrieval/expression,
repetition, auditory comprehension for phrases/sentences, single-word comprehension,
reading, writing, and functional communication) as well as pragmatic aspects of communication
on a 3-point scale. The SLP completes the scale after a questionnaire is filled out
by an informant and a structured interview is conducted with both patient and informant.
The Progressive Aphasia Language Scale (PALS)[19] also involves clinician ratings of speech–language features (motor speech and grammatical
features in spontaneous speech, naming, single-word repetition and comprehension,
and sentence repetition and comprehension) but is based on signs observed during a
prescribed set of speech–language tasks, rather than symptoms reported via an interview
or questionnaire. An algorithm using four key features from this assessment (motor
speech impairment, grammar, single-word comprehension, and sentence repetition) proved
highly accurate (96% correct) at subtyping PPA participants by variant (relative to
expert clinical diagnosis). Lastly, although not designed specifically for PPA, the
Clinical Dementia Rating (CDR),[24] a dementia severity rating scale based on a semistructured interview as well as
clinical judgment, now includes a language domain.[25] This confers additional sensitivity (relative to the original CDR) for detecting
and tracking symptoms and functional impairments in language-prominent dementias such
as PPA.
Assessment of Specific Cognitive-Linguistic Domains Using Tailored Tasks
In addition to general aphasia batteries and rating scales, specific tasks and assessments
may be utilized to further inform differential diagnosis of PPA variant (see [Table 1] for a summary of a subset of assessments/tasks). These assessments also provide
crucial information regarding spared and impaired speech–language and cognitive processes
that may be relevant when designing an intervention plan. A comprehensive battery
of such assessments might include the following components: confrontation naming,
tests of object/person knowledge, single-word and sentence comprehension measures,
repetition tasks, spontaneous speech/language production tasks, motor speech assessment,
written language measures, and assessments of nonlinguistic cognitive status. Several
assessments have been developed or adapted to measure a specific linguistic or motoric
domain in PPA, including assessments of lexical retrieval,[26] syntax,[20]
[27] nonverbal semantic processing,[28] and apraxia of speech.[29] Other assessments were developed for stroke aphasia; however, given the overlapping
symptomatology across etiologies and these measures' inclusion of normative data for
age-matched controls, they are valid instruments for detecting impairment in PPA as
well. We outline relevant assessments from each of these categories below.
Table 1
Impaired domains and predicted performance on speech–language assessments by PPA variant
|
Impaired domains by PPA variant
|
Speech–language assessments/tasks and predicted performance
|
|
Semantic variant:
Impaired confrontation naming; impaired knowledge of people and objects; surface dyslexia/dysgraphia
|
BNT[29] = Impaired performance with the presence of semantic errors
PPT[39] = Impaired performance
PPVT[41] or other single-word comprehension task = Impaired performance
NAT[26] = Spared performance
Repetition task (e.g., WAB subtest[13]) = Spared performance
Motor speech tasks[50]
[51] = Spared performance
Connected speech task = Anomic during connected speech, with empty language (e.g.,
use of the words thing and stuff); may show semantic errors (e.g., cat for dog)
Reading/Writing tasks[55] = Surface dyslexia/dysgraphia (impairment on irregular word reading and spelling,
especially for low-frequency words); may show phonologically plausible errors (e.g.,
spell tomb as toom)
|
|
Nonfluent/agrammatic variant:
Impaired grammar and/or motor speech (i.e., apraxia of speech); agrammatism in writing
|
BNT[29] = May show mild impairment with the presence of articulatory or phonological errors
PPT[39] = Spared performance
PPVT[41] or other single-word comprehension task = Spared performance
NAT[26] = Impaired performance if agrammatic
Repetition task (e.g., WAB subtest[13]) = Impaired; may show grammatical errors (e.g., omitting obligatory functors) or
motor speech errors (e.g., sound distortions)
Motor speech tasks[50]
[51] = Impaired performance with features of apraxia of speech and possible concomitant
dysarthria
Connected speech task = Simplified grammatical structures, agrammatism, and may present
with slow, effortful speech production (consistent with AOS)
Reading/Writing tasks[55] = May show worse performance on pseudowords. May show agrammatism when reading and
writing at the text level (e.g., written picture description, passage reading)
|
|
Logopenic variant:
Impaired confrontation naming; impaired repetition (particularly for sentences of
increasing length); phonological dyslexia/dysgraphia
|
BNT[29] = Impaired, often with phonological paraphasias
PPT[39] = Spared performance
PPVT[41] or other single-word comprehension task = Spared performance
NAT[26] = Spared performance
Repetition task (e.g., WAB subtest[13]) = Impaired, especially with phrases and sentences of increasing length
Motor speech tasks[50]
[51] = Spared performance
Connected speech task = May present with phonological paraphasias; pauses during instances
of word retrieval difficulty
Reading/Writing tasks[55] = Phonological dyslexia/dysgraphia (impairment most prominent on pseudowords); may
show lexicalization errors (word substituted for pseudoword)
|
Abbreviations: BNT, Boston Naming Test; NAT, Northwestern Anagram Test; PPT, Pyramids
and Palm Trees; PPVT, Peabody Picture Vocabulary Test; WAB, Western Aphasia Battery.
Assessment of Lexical Retrieval
Assessment of Lexical Retrieval
Naming impairment is a ubiquitous feature in PPA and is a core feature of both semantic
and logopenic variants. Confrontation naming may be assessed using a graded picture
naming test such as the Boston Naming Test.[30] From this measure, the severity of the naming impairment can be determined and types
of naming errors can be noted, which may assist in distinguishing among the variants
of PPA. Individuals with the semantic variant are likely to be anomic on all but the
highest frequency items, and are likely to produce superordinate or coordinate semantic
errors or to omit words.[31]
[32] These individuals are unlikely to be aided by phonemic cues and may also do poorly
when given multiple-choice options.[33] When matched for overall severity of aphasia, individuals with the logopenic variant
are likely to have naming impairment that is less severe than that of individuals
with semantic variant PPA, but more severe than those with the nonfluent/agrammatic
variant.[3] Additionally, logopenic individuals are more likely to produce phonemic paraphasias
than those with semantic variant. In the nonfluent/agrammatic variant, naming errors
may be phonetic (indicating motor speech impairment) or phonemic in nature.[34] Individuals with the logopenic and nonfluent/agrammatic variants of PPA typically
demonstrate spared semantic knowledge for items they cannot name (i.e., the ability
to circumlocute) and may be aided by phonological cues and multiple-choice options.
The Northwestern Naming Battery assesses both noun and verb production as well as
comprehension and has proven sensitive to different patterns of deficits in agrammatic
PPA (impaired verb naming and spared comprehension) versus semantic variant PPA (impaired
noun naming and comprehension).[26]
Assessment of Object/Person Knowledge and Single-Word Comprehension
Assessment of Object/Person Knowledge and Single-Word Comprehension
Impaired object/person knowledge is often a feature of semantic variant of PPA.[35]
[36]
[37]
[38] To assess object knowledge, nonverbal semantic processing assessments such as picture
association tests and picture–sound or object–function matching tests can be used.
A short version of the Pyramids and Palm Trees Test,[39] a picture association test, has proven sensitive to object knowledge deficits in
semantic variant PPA as compared with the other clinical variants. To test knowledge
of people, individuals may be asked to identify photographs of famous individuals
and celebrities.[35]
[40] Single-word comprehension is usually tested via spoken or written word-picture matching
tasks (e.g., Peabody Picture Vocabulary Test[41]). These measures are especially sensitive for identifying individuals with semantic
variant PPA, for whom single-word comprehension deficits are a core feature. By contrast,
single-word comprehension is largely spared in nonfluent/agrammatic and logopenic
variants of PPA.
Assessment of Syntax
Standardized aphasia tests such as the WAB, BDAE, and Northwestern Assessment of Verbs
and Sentences (NAVS)[42] contain sentence comprehension tasks and can be useful in identifying impairments
of receptive syntax. Impaired comprehension of syntactically complex sentences (e.g.,
subject-relative or object-relative clauses) is typical in individuals with nonfluent/agrammatic
PPA.[43] However, individuals with logopenic PPA may show impairment on items that contain
sentences of greater length, or that have lower probability,[44] due to deficits in phonological working memory. The Make A Sentence Test (MAST)
and the SEntence Comprehension Test (SECT) were designed to test syntax production
and comprehension, respectively, and have proven to correlate with grammatical difficulties
in spontaneous speech of individuals with PPA.[20] For patients with very limited output or concomitant motor speech impairment, the
Northwestern Anagram Test (NAT), which does not require spoken production, may be
used to assess expressive grammar.[27] This assessment requires individuals to arrange anagrams in the correct order to
generate sentences of varying syntactic difficulty that correspond to pictures presented
by the clinician. Notably, this assessment, in conjunction with a test of lexical
semantics (Peabody Picture Vocabulary Test), has proven effective in distinguishing
among PPA variants.[6]
[45]
Assessment of Repetition
To assess repetition, subtests or tasks from comprehensive aphasia batteries may prove
useful (e.g., WAB, BDAE). Difficulty with repetition due to dysarthria, apraxia of
speech, and/or agrammatism is characteristic of the nonfluent/agrammatic variant of
PPA.[46] By contrast, logopenic individuals have difficulty repeating words and sentences
due to deficits in phonological short-term memory.[44]
[47]
[48] As such, they are likely to perform more poorly on longer, lower probability items
and those without semantic content, such as nonwords or anomalous sentences (e.g.,
“Hairpins leap fluttering riddle games”[49]).
Evaluation of Motor Speech and Fluency
Evaluation of Motor Speech and Fluency
In addition to repetition tasks, a motor speech evaluation, such as the hierarchy
of tasks outlined by Wertz and colleagues[50] or Duffy,[51] provides information to assist in distinguishing between the nonfluent/agrammatic
and logopenic variants of PPA, each of which presents with reduced fluency of output,
but for different underlying reasons (motoric/grammatical vs. phonological). These
batteries include tasks such as diadochokinetic measures (rapid repetition of alternating
speech sounds such as “puh-tuh-kuh”) and repetition of utterances of increasing articulatory
complexity (from single sounds to long sentences), as well as multiple repetitions
of words containing difficult articulatory sequences, such as impossibility or artillery. This type of assessment can reveal characteristics of mild dysarthria or AOS, which
may not be salient in conversational speech. The presence and severity of features
of AOS may be quantified using the Apraxia of Speech Rating Scale (ASRS), which has
been implemented in patients with neurodegenerative disease.[29] Characteristic features of nonfluent/agrammatic PPA include a slow rate of articulation,
effortful or errorful speech production, and, in some cases, alterations in voice
quality or prosodic features.[46]
“Fluency” is a multidimensional construct that encapsulates several speech and language
features which may be variably disrupted in the clinical subtypes of PPA. To assess
speech–language fluency, a picture description task (such as the “Cookie Theft” picture
from the BDAE or the “Picnic Scene” from the WAB) can be used to obtain a connected
speech sample. From this measure, speech rate, utterance length, grammatical competence,
lexical retrieval ability, and motor speech features can be assessed. Speech and language
measures derived from a picture description task have been shown to aid in distinguishing
among the PPA variants.[52] Participants with semantic variant PPA will show preservation of prosodic and motoric
features of speech as well as grammar, but will demonstrate marked word retrieval
difficulty, particularly for nouns, resulting in “empty” but fluent language. Nonfluent
patients will show simplified grammar or agrammatic constructions with a relative
paucity of verbs relative to nouns. Speech fluency may also be disrupted by slowed
rate and effortful, distorted production resulting from motor speech impairment (AOS
and, in some cases, dysarthria). By contrast, individuals with the logopenic variant
will show frequent pauses for word finding, phonological paraphasias, and may demonstrate
use of paragrammatic constructions related to abandoned or rephrased utterances in
the context of word retrieval failure.
Assessment of Written Language
Assessment of Written Language
Writing and reading of single words and text should be incorporated into the PPA evaluation,
as characteristic deficits may help differentially diagnose its variants[1]
[53]
[54] and may indicate whether written language can be utilized as an alternate communication
modality. Stimuli for assessment of single-word reading and spelling should vary by
frequency (high vs. low), regularity (regular words, such as stop and irregular words, such as tomb), and lexical status (words vs. pseudowords). The Arizona Battery of Reading and
Spelling[55] is a publicly available resource (http://aphasia.arizona.edu/Aphasia_Research_Project/Assessment_Materials.html) that systematically manipulates these features. Other word lists that control for
these parameters are available in the Psycholinguistic Assessment of Language Processing
in Aphasia (PALPA).[56] Individuals with the semantic variant of PPA present with surface dyslexia/dysgraphia,
or difficulty reading/spelling irregular words, particularly those that are low in
frequency.[35]
[57]
[58]
[59] Attempts to read or spell irregular words may result in phonologically plausible
errors (e.g., choir spelled as qwire). Acquiring a written language sample in response to a picture scene can reveal agrammatism
that is not evident in spoken discourse for individuals with nonfluent/agrammatic
PPA. Individuals with the logopenic variant of PPA show pronounced deficits in reading
and spelling nonwords, which require sound-letter conversion and are particularly
taxing for the phonological system.[53] Individuals with logopenic PPA may default to real words when attempting to read
or spell nonwords, resulting in lexicalization errors, a characteristic feature of
phonological dyslexia/dysgraphia (e.g., dringe read as drink).
Assessment of Nonlinguistic Cognitive Ability
Assessment of Nonlinguistic Cognitive Ability
Assessment of cognitive status is important to establish baseline cognitive performance,
to rule out other possible diagnoses (e.g., Alzheimer's dementia), or to detect the
emergence of concomitant cognitive deficits with disease progression. Impairment of
nonlinguistic cognitive domains should be less prominent than that of language function.
However, subtle executive function deficits and other cognitive impairments may be
present.[60] Standard cognitive screening tools such as the Mini-Mental State Exam[61] or the Montreal-Cognitive Assessment[62] should be used with caution. These measures are largely language based and, as such,
may overestimate cognitive impairment in PPA.[63] Several neuropsychological assessment tools have been developed specifically for
individuals with frontotemporal dementia spectrum disorders and are freely available
to the public, including the frontotemporal lobar degeneration module[64] from the National Alzheimer's Coordinating Center (NACC; https://www.alz.washington.edu/WEB/forms_ftld.html) and a tablet-based assessment (TabCat; https://memory.ucsf.edu/tabcat), developed at the University of California San Francisco, that includes tests of
executive function, memory, visuospatial skills, and socioemotional functions. Even
a relatively brief neuropsychological battery can be informative for differential
diagnosis, which may obviate the need for lengthy batteries that may be difficult
or impossible for patients with dementia to complete.[65]
Conclusion
In this study, we have discussed assessments that may be used when evaluating the
speech–language and cognitive characteristics of individuals with PPA. Initially,
it is important that the medical team (including the SLP) establishes that the individual
meets criteria for a diagnosis of PPA. Subsequently, subtyping by clinical variant
will allow for interventions to be developed and administered with greater precision.
As clinical drug trials become more widely available for specific underlying pathologies,
accurate subtyping of PPA variant may aid in determining appropriate candidates for
these studies. Furthermore, the behavioral profile associated with each variant can
guide clinicians to tailor interventions to the individual's current profile, while
anticipating and addressing the inevitable changes that are expected to emerge.
The three variants of PPA present with unique linguistic and cognitive features that
may be discerned via a detailed case history and formal evaluation. The current consensus
criteria should be consulted when selecting assessments to ensure that the test battery
targets the established core and associated impairments characteristic of each clinical
subtype. Many of the assessments reviewed in this study were initially developed to
characterize speech–language changes secondary to stroke (e.g., WAB), or to capture
changes in cognitive status in dementia more broadly (e.g., MMSE). Nevertheless, some
assessments have been developed in the past decade to aid specifically with subtyping
PPA variant (e.g., SydBat), to evaluate deficits characteristic of each clinical variant
(e.g., NAT), and to track symptom progression in PPA (e.g., PASS). Collectively, this
compendium of assessments enables the SLP to characterize the cognitive-linguistic
features of PPA, supporting diagnostic decision making, informing treatment planning,
and helping to monitor and predict changes in communication status over time.
