Primary Progressive Apraxia Of Speech Research Articles

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.

Efficacy of LSVT LOUD® on Phonatory Control and Voice Quality in Patients with Primary Progressive Apraxia of Speech: Case Studies

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome characterized by the progressive and initially isolated or predominant onset of difficulties in the planning/programming of movements necessary for speech production and can be accompanied by dysarthria. To date, no study has used an evidence-based treatment to address phonation control in patients with PPAOS. The aim of this study was to evaluate the feasibility and efficacy of LSVT LOUD® as a treatment for phonatory control in speakers with PPAOS. Three speakers with PPAOS received LSVT LOUD® therapy, and changes in phonatory control, voice quality and prosody were measured immediately, and one, four and eight weeks after the end of the treatment. Overall, the results suggest that the treatment is feasible and could improve voice quality, intensity, and control in some patients with PPAOS. The generalization of the results is also discussed.

Progression of Nonfluent Primary Progressive Aphasia and Primary Progressive Apraxia of Speech into Corticobasal Syndrome (S43.001)

Progression of Nonfluent Primary Progressive Aphasia and Primary Progressive Apraxia of Speech into Corticobasal Syndrome (S43.001)

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

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. 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. 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. 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.

Primary Progressive Apraxia of Speech Caused by TDP-43: A Case Report.

To introduce the first case in which primary progressive apraxia of speech (PPAOS) is associated with TAR DNA-binding protein 43 (TDP-43) instead of 4-repeat tau. This patient was identified through a postmortem autopsy. Following an initial diagnostic evaluation, he participated in 3 annual research visits during which speech, language, cognitive, and neurologic assessments were administered. Neuroimaging was also acquired. Apraxia of speech was diagnosed at his initial visit with a comprehensive neurologic examination further revealing subtle motor findings in the right hand. At subsequent visits, agrammatic aphasia and motor symptoms consistent with corticobasal syndrome were evident. Cognition and behavior remained relatively intact until advanced stages. FDG-PET revealed hypometabolism in the right temporoparietal cortex and left premotor and motor cortices. There was also low-level signal in the right temporoparietal cortex on tau-PET. A sequence variation in the progranulin gene was identified (GRN c.1A>C, p.Met1). Pathologic diagnosis was TDP-43 Type A with an atypical distribution of inclusions in premotor and motor cortices. This case report demonstrates that TDP-43 Type A inclusions in an atypical distribution can present clinically as PPAOS. The sequence variation in the progranulin gene and asymmetric temporoparietal cortex involvement were the strongest indications of the unusual neuropathophysiology prior to autopsy.

Characterizing Speech Errors Across Primary Progressive Apraxia of Speech Subtypes.

Apraxia of speech (AOS) is a motor speech disorder affecting articulatory planning and speech programming. When AOS is the sole manifestation of neurodegeneration, it is termed primary progressive apraxia of speech (PPAOS). Recent work has shown that there are distinct PPAOS subtypes: phonetic, prosodic, and those that do not clearly align with either (mixed). PPAOS subtypes differ with respect to the predominating motor speech difficulties, as well as disease progression and underlying pathology. Because past studies have determined PPAOS subtype based on clinical impression, the goal of the present study was to quantitatively determine the distribution of speech error types across PPAOS subtypes in a word repetition task and to investigate how word complexity affects the type and number of speech errors across PPAOS subtypes. Forty-five patients with PPAOS (13 phonetic, 23 prosodic, and nine mixed) and 45 healthy controls produced multiple repetitions of words that varied in phonetic complexity. Sound additions, deletions, and substitutions/distortions (phonetic errors) and within-word segmentations (prosodic errors) were calculated. All three PPAOS groups produced significantly more errors than controls, but the total number of errors was comparable among subtypes. The phonetic group produced more phonetic-type errors compared to the prosodic group but comparable to the mixed group. The prosodic group produced more segmentations compared to the phonetic and mixed PPAOS groups. As word complexity increased, the total number of errors increased for PPAOS patients. The phonetic and prosodic groups were more likely to produce phonetic- and prosodic-type errors, respectively, as word complexity increased. This study provides novel quantitative data showing that PPAOS subtype can be supported by the type and distribution of speech errors in a word repetition task. This may facilitate earlier, more reliable differential diagnosis and aid in disease prognosis, as PPAOS subtypes have distinct disease trajectories.

Clinical dimensions along the non-fluent variant primary progressive aphasia spectrum.

It is debated whether primary progressive apraxia of speech (PPAOS) and progressive agrammatic aphasia (PAA) belong to the same clinical spectrum, traditionally termed non-fluent/agrammatic variant primary progressive aphasia (nfvPPA), or exist as two completely distinct syndromic entities with specific pathologic/prognostic correlates. We analysed speech, language and disease severity features in a comprehensive cohort of patients with progressive motor speech impairment and/or agrammatism to ascertain evidence of naturally occurring, clinically meaningful non-overlapping syndromic entities (e.g. PPAOS and PAA) in our data. We also assessed if data-driven latent clinical dimensions with aetiologic/prognostic value could be identified. We included 98 participants, 43 of whom had an autopsy-confirmed neuropathological diagnosis. Speech pathologists assessed motor speech features indicative of dysarthria and apraxia of speech (AOS). Quantitative expressive/receptive agrammatism measures were obtained and compared with healthy controls. Baseline and longitudinal disease severity was evaluated using the Clinical Dementia Rating Sum of Boxes (CDR-SB). We investigated the data's clustering tendency and cluster stability to form robust symptom clusters and employed principal component analysis to extract data-driven latent clinical dimensions (LCD). The longitudinal CDR-SB change was estimated using linear mixed-effects models. Of the participants included in this study, 93 conformed to previously reported clinical profiles (75 with AOS and agrammatism, 12 PPAOS and six PAA). The remaining five participants were characterized by non-fluent speech, executive dysfunction and dysarthria without apraxia of speech or frank agrammatism. No baseline clinical features differentiated between frontotemporal lobar degeneration neuropathological subgroups. The Hopkins statistic demonstrated a low cluster tendency in the entire sample (0.45 with values near 0.5 indicating random data). Cluster stability analyses showed that only two robust subgroups (differing in agrammatism, executive dysfunction and overall disease severity) could be identified. Three data-driven components accounted for 71% of the variance [(i) severity-agrammatism; (ii) prominent AOS; and (iii) prominent dysarthria]. None of these data-driven LCDs allowed an accurate prediction of neuropathology. The severity-agrammatism component was an independent predictor of a faster CDR-SB increase in all the participants. Higher dysarthria severity, reduced words per minute and expressive and receptive agrammatism severity at baseline independently predicted accelerated disease progression. Our findings indicate that PPAOS and PAA, rather than exist as completely distinct syndromic entities, constitute a clinical continuum. In our cohort, splitting the nfvPPA spectrum into separate clinical phenotypes did not improve clinical-pathological correlations, stressing the need for new biological markers and consensus regarding updated terminology and clinical classification.

Amyloid and Tau PET Positivity in Progressive Agrammatic Aphasia and Apraxia of Speech.

The agrammatic variant of primary progressive aphasia (PAA), primary progressive apraxia of speech (PPAOS), or a combination of both (AOS-PAA) are neurodegenerative disorders characterized by speech-language impairments and together compose the AOS-PAA spectrum disorders. These patients typically have an underlying 4-repeat tauopathy, although they sometimes show evidence of amyloid-β and tau deposition on PET, suggesting Alzheimer's disease (AD). Given the growing number of pharmacologic treatment options for AD, it is important to better understand the incidence of AD pathology in these patients. This study aimed to evaluate the frequency of amyloid-β and tau positivity in AOS-PAA spectrum disorders. Sixty-five patients with AOS-PAA underwent a clinical speech-language battery and PiB PET and flortaucipir PET imaging. Global PiB PET standardized uptake value ratios (SUVRs) and flortaucipir PET SUVRs from the temporal meta region of interest were compared between patient groups. For 19 patients who had died and undergone autopsy, their PET and pathology findings were also compared. The results showed that although roughly half of the patients are positive for at least one biomarker, their clinical symptoms and biomarker status were not related, suggesting that AD is not the primary cause of their neurodegeneration. All but one patient in the autopsy subset had a Braak stage of IV or less, despite four being positive on tau PET imaging. Inclusion criteria for clinical trials should specify clinical presentation or adjust the evaluation of such treatments to be specific to disease diagnosis beyond the presence of certain imaging biomarkers.

A - 87 A Neuropsychological Case Study of Primary Progressive Apraxia of Speech Versus Agrammatic Primary Progressive Aphasia.

Primary progressive apraxia of speech (PPAOS) is a lesser-known neurodegenerative disorder characterized by progressive speech production loss, affecting word articulation. Apraxic speech commonly occurs in primary progressive aphasias (PPAs) and as a result, is often misdiagnosed as agrammatic PPA (aPPA). The current case highlights the importance of neuropsychological evaluations and behavioral observations in delineating PPAOS from aPPA. The patient is a 71-year-old right-handed White female who presented with a 2-year history of language difficulties beginning with a lisp and progressing to an inability to produce words. MRI of the brain showed moderate white matter disease. Her neurocognitive profile was notable for primary deficits in expressive language, including oral/written production, verbal fluency, and repetition. Milder deficits were observed in aspects of executive functioning. Observed spontaneous speech was notable for impaired and effortful articulation with syllabically segmented prosodic speech patterns, some distortions and prosody alterations, and slow rate. All other cognitive domains were intact. Patients with PPAOS and aPPA typically score in the impaired range on tests that depend on rate and accuracy of speech. Apraxia was her most salient feature reported and observed on testing. We did not find learning and memory difficulties, which are more common in aPPA. Moreover, she had trial-and-error articulatory attempts, groping, and distorted substitutions, which are more commonly seen in PPAOS. Her speech was also devoid of grammatical errors which is another distinguishing feature. While subtle and confounded by her alcohol use and orthopedic injuries, her profile altogether appeared most consistent with PPAOS.

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 isa 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 theevidence 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 andthe review are discussed.

Neural basis of speech and grammar symptoms in non-fluent variant primary progressive aphasia spectrum.

The non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA) is a neurodegenerative syndrome primarily defined by the presence of apraxia of speech (AoS) and/or expressive agrammatism. In addition, many patients exhibit dysarthria and/or receptive agrammatism. This leads to substantial phenotypic variation within the speech-language domain across individuals and time, in terms of both the specific combination of symptoms as well as their severity. How to resolve such phenotypic heterogeneity in nfvPPA is a matter of debate. 'Splitting' views propose separate clinical entities: 'primary progressive apraxia of speech' when AoS occurs in the absence of expressive agrammatism, 'progressive agrammatic aphasia' (PAA) in the opposite case, and 'AOS + PAA' when mixed motor speech and language symptoms are clearly present. While therapeutic interventions typically vary depending on the predominant symptom (e.g. AoS versus expressive agrammatism), the existence of behavioural, anatomical and pathological overlap across these phenotypes argues against drawing such clear-cut boundaries. In the current study, we contribute to this debate by mapping behaviour to brain in a large, prospective cohort of well characterized patients with nfvPPA (n = 104). We sought to advance scientific understanding of nfvPPA and the neural basis of speech-language by uncovering where in the brain the degree of MRI-based atrophy is associated with inter-patient variability in the presence and severity of AoS, dysarthria, expressive agrammatism or receptive agrammatism. Our cross-sectional examination of brain-behaviour relationships revealed three main observations. First, we found that the neural correlates of AoS and expressive agrammatism in nfvPPA lie side by side in the left posterior inferior frontal lobe, explaining their behavioural dissociation/association in previous reports. Second, we identified a 'left-right' and 'ventral-dorsal' neuroanatomical distinction between AoS versus dysarthria, highlighting (i) that dysarthria, but not AoS, is significantly influenced by tissue loss in right-hemisphere motor-speech regions; and (ii) that, within the left hemisphere, dysarthria and AoS map onto dorsally versus ventrally located motor-speech regions, respectively. Third, we confirmed that, within the large-scale grammar network, left frontal tissue loss is preferentially involved in expressive agrammatism and left temporal tissue loss in receptive agrammatism. Our findings thus contribute to define the function and location of the epicentres within the large-scale neural networks vulnerable to neurodegenerative changes in nfvPPA. We propose that nfvPPA be redefined as an umbrella term subsuming a spectrum of speech and/or language phenotypes that are closely linked by the underlying neuroanatomy and neuropathology.

Differential Diagnosis of Primary Progressive Apraxia of Speech in a Nonnative English-Speaking Patient: A Clinical Case Study

Purpose: This case study details the approach to differential diagnosis in characterizing a progressive communication difficulty in a nonnative English-speaking patient. Method: The patient is a multilingual gentleman in his late 60s with a 3-year history of progressive difficulty speaking clearly who presented for evaluation of communication difficulties. Prior to speech evaluation, he was diagnosed with stress-related speech changes by one provider, parkinsonism by another, and primary progressive aphasia by a third provider. A thorough speech and language evaluation, including a detailed case history, was conducted. Results: The patient described a progressive difficulty in enunciating, but not coming up with words; this was present across languages spoken. On exam, the patient exhibited phonetic predominant apraxia of speech, nonverbal oral apraxia, and no more than equivocal aphasia, yielding an overall shared speech and neurologic diagnosis of primary progressive apraxia of speech. Conclusion: This case demonstrates the importance of differential diagnosis of motor speech disorders and a detailed case history, particularly when speech difficulties are the first and only neurological symptom.

Speech Motor Profiles in Primary Progressive Aphasia.

Previous research on motor speech disorders (MSDs) in primary progressive aphasia (PPA) has largely focused on patients with the nonfluent/agrammatic variant of PPA (nfvPPA), with few systematic descriptions of MSDs in variants other than nfvPPA. There has also been an emphasis on studying apraxia of speech, whereas less is known about dysarthria or other forms of MSDs. This study aimed to examine the qualitative and quantitative characteristics of MSDs in a prospective sample of individuals with PPA independent of subtype. We included 38 participants with a root diagnosis of PPA according to current consensus criteria, including one case with primary progressive apraxia of speech. Speech tasks comprised various speech modalities and levels of complexity. Expert raters used a novel protocol for auditory speech analyses covering all major dimensions of speech. Of the participants, 47.4% presented with some form of MSD. Individual speech motor profiles varied widely with respect to the different speech dimensions. Besides apraxia of speech, we observed different dysarthria syndromes, special forms of MSDs (e.g., neurogenic stuttering), and mixed forms. Degrees of severity ranged from mild to severe. We also observed MSDs in patients whose speech and language profiles were incompatible with nfvPPA. The results confirm that MSDs are common in PPA and can manifest in different syndromes. The findings emphasize that future studies of MSDs in PPA should be extended to all clinical variants and should take into account the qualitative characteristics of motor speech dysfunction across speech dimensions. https://doi.org/10.23641/asha.22555534.

Primary progressive apraxia of speech: Clinico-pathological associations of left-right hemispheric dominance (S8.008)

<h3>Objective:</h3> To determine whether there are differences in in demographics, clinicopathologic-neuroimaging or survival, between left-dominant, right-dominant, and symmetric PPAOS. <h3>Background:</h3> Primary progressive apraxia of speech (PPAOS) is a neurodegenerative syndrome associated with neuroimaging abnormalities affecting the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is unclear whether relative greater damage to premotor regions in left/right hemisphere is associated with differences in baseline and/or longitudinal features. <h3>Design/Methods:</h3> Fifty-one prospectively recruited PPAOS patients who completed [¹⁸F]-fluorodeoxyglucose PET scanning were classified as left-dominant, right-dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG-PET by independent raters. Statistical analyses were utilized to compared baseline and longitudinal features. Kaplan-Meyer curves and Cox proportional hazards were used to evaluate survival differences across groups. <h3>Results:</h3> 49% of PPAOS patients were identified as left-dominant, 31% as right-dominant, and 20% as symmetric. At baseline, there were no differences between groups. On longitudinal rates of clinical change, left-dominant PPAOS displayed a slower progression of Parkinsonian symptoms on the Unified Parkinson Disease Rating Scale-III (p=0.047), with a trend for slowest rates of progression in ideomotor apraxia (p=0.06) and motor speech severity (p=0.09) relative to other groups. Right-dominant PPAOS demonstrated the most rapid rates of progression of behavioral disturbances on the Frontal Behavioral Inventory (p=0.02), including disinhibition symptoms (p=0.02) and negative behaviors (p=0.05). The symmetric group had fastest worsening of dysarthria. There were no differences in survival, although a five-year increase in age at onset, but not group classification, was associated with shorter survival (Hazard Ratio = 1.32; p=0.007). Braak neurofibrillary tangle stage differed across groups (p=0.01). While not statistically significant, right-dominant PPAOS tended to have corticobasal degeneration (CBD) and left-dominant PPAOS had progressive supranuclear palsy (PSP) pathology at autopsy. <h3>Conclusions:</h3> Patients with PPAOS and a left-dominant pattern of hypometabolism on FDG-PET have the slowest rate of decline of clinical features. <b>Disclosure:</b> Miss Robinson has nothing to disclose. The institution of Joseph Duffy has received research support from NIH. Joseph Duffy has received publishing royalties from a publication relating to health care. Heather Clark has received personal compensation for serving as an employee of Mayo Clinic. The institution of Heather Clark has received research support from NIH. Heather Clark has received publishing royalties from a publication relating to health care. The institution of Rene Utianski has received research support from NIH. The institution of Dr. Machulda has received research support from NIH. Dr. Botha has received research support from NIH. Dr. Singh has nothing to disclose. Nha Trang Thu Pham has received personal compensation for serving as an employee of Mayo Clinic. Mr. Martin has nothing to disclose. The institution of Dr. Taner has received research support from NIH. Dr. Dickson has nothing to disclose. Dr. Lowe has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for AVID Radiopharmaceutical. Dr. Lowe has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai Inc. The institution of Dr. Lowe has received research support from AVID Radiopharmaceuticals. Dr. Whitwell has nothing to disclose. Dr. Josephs has nothing to disclose.

Acoustic analysis and neuroimaging correlates of diadochokinetic rates in mild-moderate primary progressive apraxia of speech

Speech rate can be judged clinically using diadochokinetic (DDK) tasks, such as alternating motion rates (AMR) and sequential motion rates (SMR). We evaluated whether acoustic AMR/SMR speech rates would differentiate primary progressive apraxia of speech (PPAOS) from healthy controls, and determined how DDK rates relate to phonetic and prosodic speech characteristics and brain metabolism on FDG-PET. Rate was calculated for each of three AMRs (repetitions of ‘puh’, ‘tuh’, and ‘kuh’) and for SMRs (repetitions of ‘puhtuhkuh’) for 27 PPAOS patients and 52 controls who underwent FDG-PET. PPAOS patients were slower than controls on all DDK tasks. All DDK rates correlated with apraxia of speech severity, with strongest associations with prosodic speech features. Slower DDK rates were associated with hypometabolism in the right cerebellar dentate and left supplementary motor area. Performance on AMR rate, not just SMR rate, may be impaired in mild PPAOS, but sensitivity and specificity require further study.

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.

Clinicopathological associations of hemispheric dominance in primary progressive apraxia of speech.

Primary progressive apraxia of speech (PPAOS) is associated with imaging abnormalities in the lateral premotor cortex (LPC) and supplementary motor area (SMA). It is not known whether greater involvement of these regions in either hemisphere is associated with demographics, presenting, and/or longitudinal features. In 51 prospectively recruited PPAOS patients who completed [18 F]-fluorodeoxyglucose (FDG) positron emission tomography (PET), we classified patients as left-dominant, right-dominant, or symmetric, based on visual assessment of the LPC and SMA on FDG-PET. SPM and statistical analyses of regional metabolic values were performed. Diagnosis of PPAOS was made if apraxia of speech was present and aphasia absent. Thirteen patients completed ioflupane-123I (dopamine transporter [DAT]) scans. We compared cross-sectional and longitudinal clinicopathological, genetic, and neuroimaging characteristics across the three groups, with area under the receiver-operating curve (AUROC) determined as a measure of effect size. In all, 49% of the PPAOS patients were classified as left-dominant, 31% as right-dominant, and 20% as symmetric, which was supported by results from the SPM and regional analyses. There were no differences in baseline characteristics. Longitudinally, right-dominant PPAOS showed faster rates of progression of ideomotor apraxia (AUROC0.79), behavioral disturbances (AUROC 0.84), including disinhibition symptoms (AUROC0.82) and negative behaviors (AUROC 0.82), and parkinsonism (AUROC 0.75) compared to left-dominant PPAOS. Symmetric PPAOS showed faster rates of dysarthria progression compared to left-dominant (AUROC 0.89) and right-dominant PPAOS (AUROC 0.79). Five patients showed abnormal DAT uptake. Braak neurofibrillary tangle stage differed across groups (p=0.01). Patients with PPAOS and a right-dominant pattern of hypometabolism on FDG-PET have the fastest rates of decline of behavioral and motor features.

Patient and Care Partner Ratings of Communication Participation in Frontotemporal Dementia.

Prior studies have shown communication-related participation restrictions in patients with degenerative disease do not always match clinician judgment of symptom severity. Relatedly, there is a growing body of literature documenting discrepancies between patients with dementia and care partner perception of participation restrictions. However, it is not known how care partner perceptions of communication participation restrictions match or diverge from the patient's experience, which was the topic of this study. Toward that end, 28 patients with apraxia of speech and/or dysarthria associated with primary progressive apraxia of speech, nonfluent/agrammatic primary progressive aphasia, or progressive supranuclear palsy, all types of frontotemporal dementia, were seen for speech-language examinations. The patients and their care partners were asked to independently complete the Communication Participation Item Bank (CPIB), short form, which is a 10-question survey about communication in different contexts; higher scores reflect less interference from their condition on communication. Care partners were instructed to complete the form with their perception of the patient's restrictions. The total CPIB score (maximum 30) and difference scores were calculated and visualized. The data (Figure) suggest mismatches exist in care partner and patient ratings of communication participation restrictions. Of 28 patients, only 1 pair had identical scores, each rating severe interference in all communication contexts. 57% of patients rated communication as less impacted (higher scores) compared to their family member, leaving 39% of family members rating communication as less impacted than their loved one's perception. This study lays the foundation for future research to include patient and care partner ratings when examining the benefit of impairment-based therapy, utilization of compensatory speech strategies, effectiveness of such strategies, and impact of other augmentative or alternative means of communication. The CPIB may be useful to document reduced psychosocial impact of disease and diminished burden and burnout on care partners with different intervention options. Future studies will explore possible differences between FTD phenotypes and, more specifically, whether 1) the motor speech disorder (MSD) disorder is primary or secondary to other motor impairment, 2) the nature or severity of the MSD, or 3) concomitant cognitive-communication impairment predict the existence of and/or direction of a discrepancy.

The many faces of globular glial tauopathy: A clinical and imaging study.

Globular glial tauopathy (GGT) has been associated with frontotemporal dementia syndromes; little is known about the clinical and imaging characteristics of GGT and how they differ from other non-globular glial 4-repeat tauopathies (N4GT) such as progressive supranuclear palsy (PSP) or corticobasal degeneration (CBD). For this case-control study the Mayo Clinic brain banks were queried for all cases with an autopsy-confirmed diagnosis of GGT between 1 January 2011 and 31 October 2021. Fifty patients with N4GT (30 PSP, 20 CBD) were prospectively recruited and followed by the Neurodegenerative Research Group at Mayo Clinic, Minnesota. Magnetic resonance imaging was used to characterize patterns of gray/white matter atrophy, MR-parkinsonism index, midbrain volume, and white matter hyperintensities.18 F-Fluorodeoxyglucose-, 11 C Pittsburg compound-, and 18 F-flortaucipir-positron emission tomography scans were reviewed. Twelve patients with GGT were identified: 83% were women compared to 42% in NG4T (p=0.02) with median age at death 76.5 years (range: 55-87). The most frequent clinical features were eye movement abnormalities, parkinsonism, behavioral changes followed by pyramidal tract signs and motor speech abnormalities. Lower motor neuron involvement was present in 17% and distinguished GGT from NG4T (p=0.035). Primary progressive apraxia of speech was the most frequent initial diagnosis (25%); 50% had a Parkinson-plus syndrome before death. Most GGT patients had asymmetric frontotemporal atrophy with matching hypometabolism. GGT patients had more gray matter atrophy in temporal lobes, normal MR-parkinsonism index, and larger midbrain volumes. Female sex, lower motor neuron involvement in the context of a frontotemporal dementia syndrome, and asymmetric brain atrophy with preserved midbrain might be suggestive of underlying GGT.

Functional connectivity to the premotor cortex maps onto longitudinal brain neurodegeneration in progressive apraxia of speech

Primary progressive apraxia of speech (PPAOS) is a neurodegenerative motor speech disorder affecting the ability to produce speech. If agrammatic aphasia is present, it can be referred to as the non-fluent/agrammatic variant of primary progressive aphasia (nfvPPA). We investigated whether resting-state functional MRI (rs-fMRI) connectivity from disease “epicenters” correlated with longitudinal gray matter atrophy and hypometabolism in nfvPPA and PPAOS. Eighteen nfvPPA and 23 PPAOS patients underwent clinical assessment, structural MRI, rs-fMRI, and [18F] fluorodeoxyglucose (FDG)-PET at baseline and ∼2 years follow-up. Rates of neurodegeneration in nfvPPA and PPAOS correlated with functional connectivity to the premotor, motor, and frontal cortex. Connectivity to the caudate and thalamus was more strongly associated with rates of hypometabolism than atrophy. Connectivity to the left Broca's area was more strongly associated with rates of atrophy and hypometabolism in nfvPPA. Finally, functional connectivity to a network of regions, and not to a single epicenter, correlated with rates of neurodegeneration in PPAOS and nfvPPA, suggesting similar biological mechanisms driving disease progression, with regional differences related to language.