Behavioral Treatment for Speech and Language in Primary Progressive Aphasia and Primary Progressive Apraxia of Speech: A Systematic Review.

Primary progressive aphasia (PPA) and primary progressive apraxia of speech (PPAOS) are neurodegenerative syndromes characterized by progressive decline in language or speech. There is a growing number of studies investigating speech-language interventions for PPA/PPAOS. An updated systematic evaluation of the treatment evidence is warranted to inform best clinical practice and guide future treatment research. We systematically reviewed the evidence for behavioral treatment for speech and language in this population. Reviewed articles were published in peer-reviewed journals through 31 May 2021. We evaluated level of evidence, reporting quality, and risk of bias using a modified version of the American Speech-Language Hearing Association (ASHA) Levels of Evidence, an appraisal point system, additional reporting quality and internal/external validity items, and, as appropriate, the Single Case Experimental Design Scale or the Physiotherapy Evidence Database - PsycBITE Rating Scale for Randomized and Non-Randomized Controlled Trials. Results were synthesized using quantitative summaries and narrative review. A total of 103 studies reported treatment outcomes for 626 individuals with PPA; no studies used the diagnostic label PPAOS. Most studies evaluated interventions for word retrieval. The highest-quality evidence was provided by 45 experimental and quasi-experimental studies (16 controlled group studies, 29 single-subject designs). All (k = 45/45) reported improvement on a primary outcome measure; most reported generalization (k = 34/43), maintenance (k = 34/39), or social validity (k = 17/19) of treatment for at least one participant. The available evidence supports speech-language intervention for persons with PPA; however, treatment for PPAOS awaits systematic investigation. Implications and limitations of the evidence and the review are discussed.

Patterns of hemispheric compromise in primary progressive apraxia of speech: From clinical profiling to differential diagnosis.

In this issue of European Journal of Neurology, Robinson et al. present a novel study on primary progressive apraxia of speech. The authors describe different clinicopathological profiles in patients with left-dominant, right-dominant, and bilateral atrophy of the supplementary motor area and lateral premotor cortex. This commentary discusses the importance of this evidence for understanding individual differences among these patients, distinguishing them from those with nonfluent variant primary progressive aphasia, and analyzing the relations between motor speech deficits and underlying pathology.

Neuropsychological Profiles of Patients with Progressive Apraxia of Speech and Aphasia.

OBJECTIVE: To characterize and compare the neuropsychological profiles of patients with primary progressive apraxia of speech (PPAOS) and apraxia of speech with progressive agrammatic aphasia (AOS-PAA). METHOD: Thirty-nine patients with PPAOS and 49 patients with AOS-PAA underwent formal neurological, speech, language, and neuropsychological evaluations. Cognitive domains assessed included immediate and delayed episodic memory (Wechsler Memory Scale-Third edition; Logical Memory; Visual Reproduction; Rey Auditory Verbal Learning Test), processing speed (Trail Making Test A), executive functioning (Trail Making Test B; Delis-Kaplan Executive Functioning Scale - Sorting), and visuospatial ability (Rey-Osterrieth Complex Figure copy). RESULTS: The PPAOS patients were cognitively average or higher in the domains of immediate and delayed episodic memory, processing speed, executive functioning, and visuospatial ability. Patients with AOS-PAA performed more poorly on tests of immediate and delayed episodic memory and executive functioning compared to those with PPAOS. For every 1 unit increase in aphasia severity (e.g. mild to moderate), performance declined by 1/3 to 1/2 a standard deviation depending on cognitive domain. The degree of decline was stronger within the more verbally mediated domains, but was also notable in less verbally mediated domains. CONCLUSION: The study provides neuropsychological evidence further supporting the distinction of PPAOS from primary progressive aphasia and should be used to inform future diagnostic criteria. More immediately, it informs prognostication and treatment planning.

Sub-classification of apraxia of speech in patients with cerebrovascular and neurodegenerative diseases.

Some studies have hypothesized that primary progressive apraxia of speech (ppAOS) consists of heterogeneous symptoms that can be sub-classified; however, no study has classified stroke-induced AOS (sAOS) and ppAOS according to common criteria. The purpose of this study was to elucidate the symptoms and relevant brain regions associated with sAOS and ppAOS for sub-classification. Participants included 8 patients with sAOS following lesions in the left precentral gyrus and/or underlying white matter, and 3 patients with ppAOS. All patients with sAOS could be classified into three subtypes: type I, with prominent distorted articulation; type II, with prominent prosodic abnormalities or type III, with similarly distorted articulation and prosodic abnormalities. This sub-classification was consistent with the subtypes of ppAOS proposed in previous reports. All patients with ppAOS were classified as type III, and exhibited three characteristics distinguishable from those of sAOS. First, they showed prominent lengthened syllables compared with the segmentation of syllables. Second, they could not always complete the production of multi-syllabic single words in one breath. Finally, they showed dysfunctional lesions in the bilateral supplementary motor area. We conclude that sAOS and ppAOS can be sub-classified and are universal symptoms that are common between the English and Japanese populations.

The yes-no reversal phenomenon in patients with primary progressive apraxia of speech.

Patients who have a yes-no reversal respond "yes" when they mean no and vice versa. The unintentional response can be made both verbally and with gestures (e.g., head shake or nod, thumbs up or down). Preliminary reports associate this phenomenon with 4-repeat tauopathies including primary progressive apraxia of speech (PPAOS), nonfluent/agrammatic primary progressive aphasia, and corticobasal syndrome; however, the significance and timing of this symptom relative to others are not well understood. Whereas some accounts associate yes-no reversals with other binary reversals (e.g., up/down, hot/cold) and attribute the reversals to disturbances of selection within the language system, others implicate more general inhibitory control processes. Here, we compared clinical and neuroimaging findings across 30 patients with PPAOS (apraxia of speech in the absence of aphasia), 15 of whom had a yes-no reversal complaint and 15 who did not. The two groups did not differ on any of the language or motor speech measures; however, patients who had the yes-no reversal received lower scores on the Frontal Assessment Battery and motor assessments. They also had greater hypometabolism in the left supplementary motor area and bilateral caudate nuclei on [18F]-fluorodeoxyglucose PET, but only the right caudate nucleus cluster survived correction for multiple comparisons. We interpret these results to suggest that the yes-no reversal phenomenon is associated with cognitive abilities that are supported by the frontostriatal network; more specifically, impaired response inhibition.

Progression to corticobasal syndrome: a longitudinal study of patients with nonfluent primary progressive aphasia and primary progressive apraxia of speech.

BACKGROUND AND OBJECTIVES: Nonfluent variant primary progressive aphasia (nfvPPA) and primary progressive apraxia of speech (PPAOS) can be precursors to corticobasal syndrome (CBS). Details on their progression remain unclear. We aimed to examine the clinical and neuroimaging evolution of nfvPPA and PPAOS into CBS. METHODS: We conducted a retrospective longitudinal study in 140 nfvPPA or PPAOS patients and applied the consensus criteria for possible and probable CBS for every visit, evaluating limb rigidity, akinesia, limb dystonia, myoclonus, ideomotor apraxia, alien limb phenomenon, and nonverbal oral apraxia (NVOA). Given the association of NVOA with AOS, we also modified the CBS criteria by excluding NVOA and assigned every patient to either a progressors or non-progressors group. We evaluated the frequency of every CBS feature by year from disease onset, and assessed gray and white matter volume loss using SPM12. RESULTS: Asymmetric akinesia, NVOA, and limb apraxia were the most common CBS features that developed; while limb dystonia, myoclonus, and alien limb were rare. Eighty-two patients progressed to possible CBS; only four to probable CBS. nfvPPA and PPAOS had a similar proportion of progressors, although nfvPPA progressed to CBS earlier (p-value = 0.046), driven by an early appearance of limb apraxia (p-value = 0.0041). The non-progressors and progressors both showed premotor/motor cortex involvement at baseline, with spread into prefrontal cortex over time. DISCUSSION: An important proportion of patients with nfvPPA and PPAOS progress to possible CBS, while they rarely develop features of probable CBS even after long follow-up.

Coming to Terms with a Conundrum: A Case of Primary Progressive Apraxia of Speech due to Corticobasal Degeneration?

Primary progressive apraxia of speech (PPAOS) is a progressive disorder impairing the motor speech act leaving linguistic function unattained. Although apraxia of speech frequently co-occurs with other neurodegenerative conditions, PPAOS defines a clinical syndrome where apraxia of speech is the sole or prominent symptom for much of the disease's natural history. Mounting evidence is beginning to fully define this disease as the epiphenomenon of 4-repeat (4R) tau pathology although other pathologic signatures have been reported. Indeed, PPAOS patients generally present a parkinsonian syndrome late into their natural history mostly qualifying for either corticobasal syndrome (CBS) or progressive supranuclear palsy (PSP). This is starting to be reflected in diagnostic criteria for PSP, namely, in the PSP speech and language (SL) subcategory; however, this inclusion is not reflected for CBS. Here, we present a single case of a patient with PPAOS and her clinical follow-up lasting 6 years, from the time she sought our attention to her death which occurred 8 years into the disease. PPAOS was the only and prominent symptom for most of the illness with extrapyramidal signs overtly presenting in the last months of its course. Clinical evaluation, imaging, genetic, and cerebrospinal fluid biomarkers all pointed toward an underlying CBD pathology, albeit the eventual anatomopathological confirmation was not performed. Had her clinical course been more suggestive of PSP, she would have qualified for criteria as PSP-SL. Our case therefore suggests the hypothetic need to discuss the broadening of the existing CBS criteria to encompass isolated PPAOS.

Primary Progressive Apraxia of Speech: From Recognition to Diagnosis and Care.

BACKGROUND: Apraxia of speech (AOS) can be caused by neurodegenerative disease and sometimes is its presenting sign (i.e., primary progressive apraxia of speech, PPAOS). During the last several decades our understanding of PPAOS has evolved from clinical recognition to a fuller understanding of its core and associated clinical features, its distinction from but relationship with primary progressive aphasia, its temporal course and eventual progression to include other neurological deficits, and its neuroimaging correlates and underlying pathology. AIMS: This paper provides a comprehensive summary of the literature that has built the current knowledge base about PPAOS and progressive AOS as it co-occurs with progressive aphasia. It reviews the history of its emergence as a recognized syndrome; its relationship with the agrammatic/nonfluent variant of primary progressive aphasia; its salient perceptual features and subtypes; the acoustic and structural/physiological imaging measures that index its presence, severity, and distinction from aphasia; and principles and available data regarding its management and care. MAIN CONTRIBUTION: A broad summary of what is known about AOS as a manifestation of neurodegenerative disease. CONCLUSIONS: Primary progressive apraxia of speech is a recognizable syndrome that can be distinguished from other neurodegenerative conditions that affect speech and language.

Electroencephalography in Primary Progressive Aphasia and Apraxia of Speech.

BACKGROUND: Past research has demonstrated that electroencephalography (EEG) is sensitive to what we now know as Primary Progressive Aphasia (PPA); however, the EEG profiles of patients with Primary Progressive Apraxia of Speech (PPAOS) and PPA, in the context of current consensus criteria, have not been studied. AIMS: The primary goal of this study was to explore the EEG profiles of patients of the nonfluent/ agrammatic variant of PPA (agPPA) and PPAOS. METHODS AND PROCEDURES: Three patients with agPPA and five patients with PPAOS (two with aphasia) completed a head MRI scan and clinical EEG recording. Clinical radiologists and electrophysiologists reviewed respective imaging, blinded to clinical diagnosis. OUTCOMES AND RESULTS: Patients with PPAOS who did not have aphasia had normal EEGs, while those with aphasia demonstrated theta slowing. Patients with agPPA also showed theta slowing, with one exception. MRI scans showed non-specific, age-related changes across clinical presentations. CONCLUSIONS: This preliminary study suggests theta slowing is consistent with neurodegenerative aphasia, but not isolated apraxia of speech. EEG is a low-cost mechanism to identify possible biomarkers for use when clinical severity limits behavioral examinations or expert examiners are unavailable.

Tau-PET imaging with [18F]AV-1451 in primary progressive apraxia of speech.

Apraxia of speech is a motor speech disorder characterized by combinations of slow speaking rate, abnormal prosody, distorted sound substitutions, and trial-and-error articulatory movements. Apraxia of speech is due to abnormal planning and/or programming of speech production. It is referred to as primary progressive apraxia of speech (PPAOS) when it is the only symptom of a neurodegenerative condition. Past reports suggest an association of PPAOS with primary 4-repeat (4R) tau (e.g., progressive supranuclear palsy, corticobasal degeneration), rather than amyloid, pathology. The goal of the current study was to investigate the distribution of tau tracer uptake using [18F]AV-1451 positron emission tomography (PET) imaging in patients with PPAOS. Fourteen PPAOS patients underwent [18F]AV-1451 PET (tau-PET) imaging, [C11] Pittsburgh Compound B (PiB) PET and structural MRI and were matched 3:1 by age and sex to 42 cognitively normal controls. Tau-PET uptake was assessed at the region-of-interest (ROI) level and at the voxel-level. The PPAOS group (n = 14) showed increased tau-PET uptake in the precentral gyrus, supplementary motor area and Broca's area compared to controls. To examine whether tau deposition in Broca's area was related to the presence of aphasia, we examined a subgroup of the PPAOS patients who had predominant apraxia of speech, with concomitant aphasia (PPAOSa; n = 7). The PPAOSa patients showed tau-PET uptake in the same regions as the whole group. However, the remaining seven patients who did not have aphasia showed uptake only in superior premotor and precentral cortices, with no uptake observed in Broca's area. This cross-sectional study demonstrates that elevated tau tracer uptake is observed using [18F]AV-1451 in PPAOS. Further, it appears that [18F]AV-1451 is sensitive to the regional distribution of tau deposition in different stages of PPAOS, given the relationship between tau signal in Broca's area and the presence of aphasia.

Prosodic and phonetic subtypes of primary progressive apraxia of speech.

Primary progressive apraxia of speech (PPAOS) is a clinical syndrome in which apraxia of speech is the initial indication of neurodegenerative disease. Prior studies of PPAOS have identified hypometabolism, grey matter atrophy, and white matter tract degeneration in the frontal gyri, precentral cortex, and supplementary motor area (SMA). Recent clinical observations suggest two distinct subtypes of PPAOS may exist. Phonetic PPAOS is characterized predominantly by distorted sound substitutions. Prosodic PPAOS is characterized predominantly by slow, segmented speech. Demographic, clinical, and neuroimaging data (MRI, DTI, and FDG-PET) were analyzed to validate these subtypes and explore anatomic correlates. The Phonetic subtype demonstrated bilateral involvement of the SMA, precentral gyrus, and cerebellar crus. The Prosodic subtype demonstrated more focal involvement in the SMA and right superior cerebellar peduncle. The findings provide converging evidence that differences in the reliably determined predominant clinical characteristics of AOS are associated with distinct imaging patterns, independent of severity.

Temporal acoustic measures distinguish primary progressive apraxia of speech from primary progressive aphasia.

The purpose of this study was to determine if acoustic measures of duration and syllable rate during word and sentence repetition, and a measure of within-word lexical stress, distinguish speakers with primary progressive apraxia of speech (PPAOS) from nonapraxic speakers with the agrammatic or logopenic variants of primary progressive aphasia (PPA), and control speakers. Results revealed that the PPAOS group had longer durations and reduced rate of syllable production for most words and sentences, and the measure of lexical stress. Sensitivity and specificity indices for the PPAOS versus the other groups were highest for longer multisyllabic words and sentences. For the PPAOS group, correlations between acoustic measures and perceptual ratings of AOS were moderately high to high. Several temporal measures used in this study may aid differential diagnosis and help quantify features of PPAOS that are distinct from those associated with PPA in which AOS is not present.

Primary Progressive Orofacial Apraxia: A Ten-Year Long Follow-Up Case Report.

Orofacial apraxia (OA) as the main symptom in neurodegenerative disorders has not been yet reported. We present the case of a woman with a 22-month long history of isolated OA, studied with cerebrospinal fluid biomarkers and repeated clinical, neuropsychological, and morpho-functional evaluations. Baseline morpho-functional neuroimages revealed a left frontal operculum hypoperfusion with a widespread fronto-temporal involvement at follow-up. Cerebrospinal fluid concentrations of tau and amyloid-ß were normal. The ten-year long clinical observation disclosed progressive OA worsening and the late onset of frontal functions impairment and extrapyramidal signs. The early and late stages of a neurodegenerative syndrome with OA as the main clinical feature were characterized.

Motor Speech Disorders Associated with Primary Progressive Aphasia.

BACKGROUND: Primary progressive aphasia (PPA) and conditions that overlap with it can be accompanied by motor speech disorders. Recognition and understanding of motor speech disorders can contribute to a fuller clinical understanding of PPA and its management as well as its localization and underlying pathology. AIMS: To review the types of motor speech disorders that may occur with PPA, its primary variants, and its overlap syndromes (progressive supranuclear palsy syndrome, corticobasal syndrome, motor neuron disease), as well as with primary progressive apraxia of speech. MAIN CONTRIBUTION: The review should assist clinicians' and researchers' understanding of the relationship between motor speech disorders and PPA and its major variants. It also highlights the importance of recognizing neurodegenerative apraxia of speech as a condition that can occur with little or no evidence of aphasia. CONCLUSION: Motor speech disorders can occur with PPA. Their recognition can contribute to clinical diagnosis and management of PPA and to understanding and predicting the localization and pathology associated with PPA variants and conditions that can overlap with them.