Botha, Hugo

Purpose Individuals with primary progressive apraxia of speech (AOS) have AOS in which disruptions in articulation and prosody predominate the speech pattern. Many develop aphasia and/or dysarthria later in the disease course. The aim of this study was to describe the communication limitations in these patients, as measured by (a) the patient via the Communicative Participation Item Bank (CPIB) and (b) the speech-language pathologist via the American Speech-Language-Hearing Association's (ASHA) Functional Communication Measures (FCMs) and an adapted motor speech disorder (MSD) severity rating. Method Speech and language evaluations were completed for 24 patients with progressive AOS ( n = 7 with isolated AOS; n = 17 with a combination of AOS and aphasia). Descriptive comparisons were utilized to evaluate differences in communication measures among patients with various combinations of MSDs and aphasia. Differences associated with phonetic predominant or prosodic predominant AOS were also examined. Across the entire cohort, correlations were calculated between the participation ratings and other clinical assessment measures. Results The CPIB reflected greater limitations for those with aphasia and AOS compared to isolated AOS, but was not notably different when dysarthria occurred with AOS ( n = 9/24). Across the cohort, there were statistically significant correlations between the CPIB and ASHA FCM–Motor Speech and Language Expression ratings and the MSD severity rating. The CPIB did not correlate with the ASHA FCM–Language Comprehension or other speech-language measures. Conclusions Patients with neurodegenerative AOS experience reduced participation in communication that is further exacerbated by co-occurring language deficits. The study suggests measures of severity cannot be assumed to correlate with measures of participation restrictions and offers a foundation for further research examining the day-to-day sequela of progressive speech and language disorders. Supplemental Material https://doi.org/10.23641/asha.12743252

Abstract Clinical trials with anti-tau drugs will need to target individuals at risk of accumulating tau. Our objective was to identify variables available in a research setting that predict future rates of tau PET accumulation separately among individuals who were either cognitively unimpaired or cognitively impaired. All 337 participants had: a baseline study visit with MRI, amyloid PET, and tau PET exams, at least one follow-up tau PET exam; and met clinical criteria for membership in one of two clinical diagnostic groups: cognitively unimpaired (n = 203); or cognitively impaired (n = 134, a combined group of participants with either mild cognitive impairment or dementia with Alzheimer’s clinical syndrome). Our primary analyses were in these two clinical groups; however, we also evaluated subgroups dividing the unimpaired group by normal/abnormal amyloid PET and the impaired group by clinical phenotype (mild cognitive impairment, amnestic dementia, and non-amnestic dementia). Linear mixed effects models were used to estimate associations between age, sex, education, APOE genotype, amyloid and tau PET standardized uptake value ratio (SUVR), cognitive performance, cortical thickness, and white matter hyperintensity volume at baseline, and the rate of subsequent tau PET accumulation. Log-transformed tau PET SUVR was used as the response and rates were summarized as annual per cent change. A temporal lobe tau PET meta-region of interest was used. In the cognitively unimpaired group, only higher baseline amyloid PET was a significant independent predictor of higher tau accumulation rates (P < 0.001). Higher rates of tau accumulation were associated with faster rates of cognitive decline in the cognitively unimpaired subgroup with abnormal amyloid PET (P = 0.03), but among the subgroup with normal amyloid PET. In the cognitively impaired group, younger age (P = 0.02), higher baseline amyloid PET (P = 0.05), APOE ε4 (P = 0.05), and better cognitive performance (P = 0.05) were significant independent predictors of higher tau accumulation rates. Among impaired individuals, faster cognitive decline was associated with faster rates of tau accumulation (P = 0.01). While we examined many possible predictor variables, our results indicate that screening of unimpaired individuals for potential inclusion in anti-tau trials may be straightforward because the only independent predictor of high tau rates was amyloidosis. In cognitively impaired individuals, imaging and clinical variables consistent with early onset Alzheimer’s disease phenotype were associated with higher rates of tau PET accumulation suggesting this may be a highly advantageous group in which to conduct proof-of-concept clinical trials that target tau-related mechanisms. The nature of the dementia phenotype (amnestic versus non-amnestic) did not affect this conclusion.

Abstract We report a group of patients presenting with a progressive dementia syndrome characterized by predominant dysfunction in core executive functions, relatively young age of onset and positive biomarkers for Alzheimer’s pathophysiology. Atypical frontal, dysexecutive/behavioural variants and early-onset variants of Alzheimer’s disease have been previously reported, but no diagnostic criteria exist for a progressive dysexecutive syndrome. In this retrospective review, we report on 55 participants diagnosed with a clinically defined progressive dysexecutive syndrome with 18F-fluorodeoxyglucose-positron emission tomography and Alzheimer’s disease biomarkers available. Sixty-two per cent of participants were female with a mean of 15.2 years of education. The mean age of reported symptom onset was 53.8 years while the mean age at diagnosis was 57.2 years. Participants and informants commonly referred to initial cognitive symptoms as ‘memory problems’ but upon further inquiry described problems with core executive functions of working memory, cognitive flexibility and cognitive inhibitory control. Multi-domain cognitive impairment was evident in neuropsychological testing with executive dysfunction most consistently affected. The frontal and parietal regions which overlap with working memory networks consistently demonstrated hypometabolism on positron emission tomography. Genetic testing for autosomal dominant genes was negative in all eight participants tested and at least one APOE ε4 allele was present in 14/26 participants tested. EEG was abnormal in 14/17 cases with 13 described as diffuse slowing. Furthermore, CSF or neuroimaging biomarkers were consistent with Alzheimer’s disease pathophysiology, although CSF p-tau was normal in 24% of cases. Fifteen of the executive predominate participants enrolled in research neuroimaging protocols and were compared to amnestic (n = 110), visual (n = 18) and language (n = 7) predominate clinical phenotypes of Alzheimer’s disease. This revealed a consistent pattern of hypometabolism in parieto-frontal brain regions supporting executive functions with relative sparing of the medial temporal lobe (versus amnestic phenotype), occipital (versus visual phenotype) and left temporal (versus language phenotype). We propose that this progressive dysexecutive syndrome should be recognized as a distinct clinical phenotype disambiguated from behavioural presentations and not linked specifically to the frontal lobe or a particular anatomic substrate without further study. This clinical presentation can be due to Alzheimer’s disease but is likely not specific for any single aetiology. Diagnostic criteria are proposed to facilitate additional research into this understudied clinical presentation.

Purpose The primary aim was to examine the utility of the Western Aphasia Battery–Revised (WAB-R; Kertesz, 2007 ) for classifying variants of primary progressive aphasia (PPA). Traditional WAB-R metrics of Aphasia Quotient (AQ), subtest scores, WAB-R classification, and several novel metrics were examined. A secondary aim was to examine these same WAB-R metrics in individuals with primary progressive apraxia of speech (PPAOS). Method A retrospective analysis of WAB-R records from 169 participants enrolled in a study of neurodegenerative speech and language disorders was conducted. PPA/PPAOS classification was determined by consensus review of speech, language, and cognitive profiles. Scores on each of the WAB-R subtests were obtained to derive AQ, WAB-R aphasia profile, and 3 ratios reflecting relative performance on subtests. Results Mean AQ was significantly higher in the PPAOS group compared to all PPA variants except primary fluent aphasia. AQ above the normal cutoff was observed for 20% of participants with PPA. Significant main effects of group were noted for each of the subtests. Follow-up comparisons most frequently discriminated PPAOS, primary agrammatic aphasia (PAA), and logopenic progressive aphasia. Primary fluent aphasia and semantic dementia (SD) subtest scores were less distinctive, with the exception of Naming for SD, which was significantly lower than for PAA and PPAOS. When the WAB-R AQ detected aphasia, a classification of anomic aphasia was most frequently observed; this pattern held true for each of the PPA variants. The mean Information Content:Naming ratio was highest for SD, and the mean Comprehension:Fluency ratio was highest for PAA. Conclusions In the current study, AQ underestimated the presence of PPA and WAB-R classification did not distinguish among PPA classification determined by consensus. Performance on individual subtests and relative performance across subtests demonstrated inconsistent alignment with PPA classification. We conclude the WAB-R in isolation is inadequate to detect or characterize PPA. We instead suggest utilizing the WAB-R as 1 component of a comprehensive language and motor speech assessment when PPA is suspected.