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Background: A definitive diagnosis of progressive supranuclear palsy (PSP) can only be established through neuropathological evaluations where four cardinal tau lesions are identified. Relationships between regional tau burden and disease duration/age at death is unclear., Objective: To investigate relationships between tau burden in different brain regions and disease duration and age at death in PSP and determine whether association are influenced by PSP subtype (subcortical/cortical) or co-pathologies., Methods: We identified 45 patients with definite PSP who were evaluated at Mayo Clinic between 2009 and 2023, died and underwent histopathological evaluation. We performed semi-quantitative lesion count for each of four cardinal lesions (pretangles/globose neurofibrillary tangles, threads, tufted astrocytes, and coiled bodies) across 10 brain regions. We fit Bayesian linear hierarchical regression models to estimate the relationship between total pathological burden, and disease duration and age at death by region and the influence of subtype and co-pathologies., Results: Of the 45 patients, 18 (40 %) were female. Median age at death was 75 (56-87) years and median disease duration was 8 (3,15) years. Younger age at death was associated with greater total tau burden in the pallidum, red nucleus, striatum, and subthalamic nucleus (all p ≤ 0.01). Shorter disease duration was associated with greater total tau burden in the red nucleus (p = 0.05). There was no evidence for a difference in association between lesion types. PSP subtype and co-pathologies did not influence associations., Conclusions: The findings from this study suggest that age and disease duration influence burden of tau pathology in subcortical regions in PSP., Competing Interests: Declaration of competing interest As the corresponding author I confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. We have no declaration of competing interest pertinent to this study. I confirm that I take full responsibility for the data, the analyses and interpretation, and the conduct of the research. I further confirm that the manuscript has been read and approved for submission by all named authors., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Transcribing disordered speech can be useful when diagnosing motor speech disorders such as primary progressive apraxia of speech (PPAOS), who have sound additions, deletions, and substitutions, or distortions and/or slow, segmented speech. Since transcribing speech can be a laborious process and requires an experienced listener, using automatic speech recognition (ASR) systems for diagnosis and treatment monitoring is appealing. This study evaluated the efficacy of a readily available ASR system (wav2vec 2.0) in transcribing speech of PPAOS patients to determine if the word error rate (WER) output by the ASR can differentiate between healthy speech and PPAOS and/or among its subtypes, whether WER correlates with AOS severity, and how the ASR's errors compare to those noted in manual transcriptions., Method: Forty-five patients with PPAOS and 22 healthy controls were recorded repeating 13 words, 3 times each, which were transcribed manually and using wav2vec 2.0. The WER and phonetic and prosodic speech errors were compared between groups, and ASR results were compared against manual transcriptions., Results: Mean overall WER was 0.88 for patients and 0.33 for controls. WER significantly correlated with AOS severity and accurately distinguished between patients and controls but not between AOS subtypes. The phonetic and prosodic errors from the ASR transcriptions were also unable to distinguish between subtypes, whereas errors calculated from human transcriptions were. There was poor agreement in the number of phonetic and prosodic errors between the ASR and human transcriptions., Conclusions: This study demonstrates that ASR can be useful in differentiating healthy from disordered speech and evaluating PPAOS severity but does not distinguish PPAOS subtypes. ASR transcriptions showed weak agreement with human transcriptions; thus, ASR may be a useful tool for the transcription of speech in PPAOS, but the research questions posed must be carefully considered within the context of its limitations., Supplemental Material: https://doi.org/10.23641/asha.26359417.

Background: Primary progressive aphasia (PPA) defines a group of neurodegenerative disorders characterised by language decline. Three PPA variants correlate with distinct underlying pathologies: semantic variant PPA (svPPA) with transactive response DNA-binding protein of 43 kD (TDP-43) proteinopathy, agrammatic variant PPA (agPPA) with tau deposition and logopenic variant PPA (lvPPA) with Alzheimer's disease (AD). Our objectives were to differentiate PPA variants using clinical and neuroimaging features, assess progression and evaluate structural MRI and a novel 18-F fluorodeoxyglucose positron emission tomography (FDG-PET) image decomposition machine learning algorithm for neuropathology prediction., Methods: We analysed 82 autopsied patients diagnosed with PPA from 1998 to 2022. Clinical histories, language characteristics, neuropsychological results and brain imaging were reviewed. A machine learning framework using a k -nearest neighbours classifier assessed FDG-PET scans from 45 patients compared with a large reference database., Results: PPA variant distribution: 35 lvPPA (80% AD), 28 agPPA (89% tauopathy) and 18 svPPA (72% frontotemporal lobar degeneration-TAR DNA-binding protein (FTLD-TDP)). Apraxia of speech was associated with 4R-tauopathy in agPPA, while pure agrammatic PPA without apraxia was linked to 3R-tauopathy. Longitudinal data revealed language dysfunction remained the predominant deficit for patients with lvPPA, agPPA evolved to corticobasal or progressive supranuclear palsy syndrome (64%) and svPPA progressed to behavioural variant frontotemporal dementia (44%). agPPA-4R-tauopathy exhibited limited pre-supplementary motor area atrophy, lvPPA-AD displayed temporal atrophy extending to the superior temporal sulcus and svPPA-FTLD-TDP had severe temporal pole atrophy. The FDG-PET-based machine learning algorithm accurately predicted clinical diagnoses and underlying pathologies., Conclusions: Distinguishing 3R-taupathy and 4R-tauopathy in agPPA may rely on apraxia of speech presence. Additional linguistic and clinical features can aid neuropathology prediction. Our data-driven brain metabolism decomposition approach effectively predicts underlying neuropathology., Competing Interests: Competing interests: DSK serves on a Data Safety Monitoring Board for the DIAN study. He served on a Data Safety Monitoring Board for a tau therapeutic for Biogen but receives no personal compensation. He is a site investigator in the Biogen aducanumab trials. He is an investigator in a clinical trial sponsored by Lilly Pharmaceuticals and the University of Southern California. He serves as a consultant for Samus Therapeutics, Roche and Alzeca Biosciences but receives no personal compensation. RCP serves as a consultant for Roche, Genentech, Nestle, Eli Lilly and Co and Eisai, and receives publishing royalties from Mild Cognitive Impairment (Oxford University Press, 2003) and UpToDate. BFB receives honoraria for SAB activities for the Tau Consortium; is a site investigator for clinical trials sponsored by Alector, Biogen and Transposon; and receives research support from NIH. GSD serves as a consultant for Parabon NanoLabs, as a topic editor (Dementia) for DynaMed (EBSCO) and as the clinical director of the Anti-NMDA Receptor Encephalitis Foundation (Canada, uncompensated). He is the co-Project PI for a clinical trial in Anti-NMDA Receptor Encephalitis, which receives support from Horizon Pharmaceuticals. He has developed educational materials for PeerView Media and Continuing Education. He owns stock in ANI Pharmaceuticals. GSD’s institution has received support from Eli Lilly for GSD’s development and participation in an educational event promoting early diagnosis of symptomatic Alzheimer's disease. WKK was supported in part by NIH funding. DWD, DTJ, KAJ and JLW received research funding from the NIH and declared no competing financial interests. MEM is a consultant for AVID Radiopharmaceuticals. She receives support from the NIH/NIA and Eli Lilly. NRG-R receives royalties from UpToDate, has participated in multicentre therapy studies sponsored by Biogen, TauRx, AbbVie, Novartis and Lilly, and he receives research support from NIH. JAF is on the OSMB for the SWAN-Aging Study, serves as a consultant for Medtronic and received NIH funding. JG-R serves on the DSMB for STROKENET, is a site investigator for a trial sponsored by Eisai and the NIH, and he receives research support from the NIH., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

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 [ 18 F]-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., Competing Interests: Declaration of competing interest The authors do not have any relevant conflicts of interest to disclose at the time of submission., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Patients with classic-onset corticobasal syndrome (CBS) present with asymmetric limb apraxia and parkinsonism. We have, however, observed patients who initially present with speech and/or language (SL) problems and several years later develop CBS (i.e., SL-onset CBS). We aimed to compare clinical, neuroimaging and pathological characteristics of classic-onset CBS with SL-onset CBS., Methods: We conducted a retrospective cohort study of 62 patients who met criteria for CBS (17 presented with classic-onset CBS and 45 had SL-onset CBS). We compared demographics, clinical characteristics, and grey and white matter volume loss with SPM12 between groups and assessed pathology and corticobasal degeneration (CBD) pathological lesion counts in patients who had died and undergone autopsy., Results: Median age at CBS diagnosis was 66.4 years in classic-onset CBS and 73.6 years in SL-onset CBS. Classic-onset CBS had higher frequencies of dystonia, myoclonus, and alien limb phenomenon, while SL-onset CBS had a higher frequency of vertical supranuclear gaze palsy. Both groups showed smaller frontoparietal volumes than controls, with SL-onset CBS having greater volume loss in the left supplementary motor area than classic-onset CBS. All three classic-onset CBS cases with autopsy (100 %) had CBD pathology while 8/21 of SL-onset CBS cases (38 %) had CBD. Pathological lesion burden (including astrocytic plaques) did not differ between classic-onset and SL-onset CBS., Conclusion: Classic-onset and SL-onset CBS appear to be different syndromes, with the former being a more profuse motor syndrome. The more widespread volume loss in SL-onset CBS likely reflects longer disease course., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Keith A. Josephs reports financial support was provided by National Institute on Deafness and Other Communication Disorders. Jennifer L. Whitwell reports financial support was provided by National Institute on Deafness and Other Communication Disorders. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background and Purpose: Primary lateral sclerosis (PLS) is a neurodegenerative disorder that primarily affects the central motor system. In rare cases, clinical features of PLS may overlap with those of progressive supranuclear palsy (PSP). We investigate neuroimaging features that can help distinguish PLS with overlapping features of PSP (PLS-PSP) from PSP., Methods: Six patients with PLS-PSP were enrolled between 2019 and 2023. We compared their clinical and neuroimaging characteristics with 18 PSP-Richardson syndrome (PSP-RS) patients and 20 healthy controls. Magnetic resonance imaging, 18 F-flortaucipir positron emission tomography (PET), quantitative susceptibility mapping, and diffusion tensor imaging tractography (DTI) were performed to evaluate eight brain regions of interest. Area under the receiver operating characteristic curve (AUROC) was calculated., Results: Five of the six PLS-PSP patients (83.3%) were male. Median age at symptom onset was 61.5 (52.5-63) years, and all had mixed features of PLS and PSP. Volumes of the pallidum, caudate, midbrain, and cerebellar dentate were smaller in PSP-RS than PLS-PSP, providing good discrimination (AUROC = 0.75 for all). The susceptibilities in pallidum, midbrain, and cerebellar dentate were greater in PSP-RS compared to PLS-PSP, providing excellent discrimination (AUROC ≥ 0.90 for all). On DTI, fractional anisotropy (FA) in the posterior limb of the internal capsule from the corticospinal tract was lower in PLS-PSP compared to PSP-RS (AUROC = 0.86), but FA in the superior cerebellar peduncle was lower in PSP-RS (AUROC = 0.95). Pallidum flortaucipir PET uptake was greater in PSP-RS compared to PLS-PSP (AUROC = 0.74)., Conclusions: Regional brain volume, tractography, and magnetic susceptibility, but not tau-PET, are useful in distinguishing PLS-PSP from PSP., (© 2024 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Purpose: We describe the communication challenges of four patients with a neurodegenerative disorder consistent with behavioral variant frontotemporal dementia (bvFTD), characterized by early behavioral and personality changes. By describing their clinical profiles, we identify common barriers to functional communication in this population and provide recommendations for how speech-language pathologists (SLPs) might contribute to minimizing them., Method: Four patients with bvFTD were selected from a cohort of patients with progressive communication impairments. Three of them returned for at least one follow-up visit. Case histories are presented along with the results of comprehensive speech and language, neuropsychological, and neurological testing., Results: At the time of initial evaluation, patients were between the ages of 54 and 66 years and had been experiencing symptoms for 1.5-6 years. Consistent with their bvFTD diagnoses, all patients had prominent behavioral and personality changes that impacted communication. Patients 1 and 2 also had mild aphasia at enrollment, primarily characterized by anomia and loss of word meaning. Patients 3 and 4 both had apraxia of speech and moderate-to-severe aphasia at enrollment with prominent anomia and agrammatism. All four patients had impaired executive functioning and relative sparing of visuospatial skills; episodic memory was also impaired for Patients 2 and 4. Even though functional communication was progressively limited for all patients, none of them received regular support from an SLP., Conclusions: This case series adds to a scant, but growing, literature demonstrating that patients with bvFTD have communication impairments. SLPs are uniquely positioned to identify barriers to functional communication and to provide tailored strategy training to the patients and their care partners over the course of their disease. Systematic evaluation of the efficacy of treatment in this population would be valuable., Supplemental Material: https://doi.org/10.23641/asha.25933762.

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., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Progressive apraxia of speech (PAOS) is a 4R tauopathy characterized by difficulties with motor speech planning. Neurodegeneration in PAOS targets the premotor cortex, particularly the supplementary motor area (SMA), with degeneration of white matter (WM) tracts connecting premotor and motor cortices and Broca's area observed on diffusion tensor imaging (DTI). We aimed to assess flortaucipir uptake across speech-language-related WM tracts identified using DTI tractography in PAOS. Twenty-two patients with PAOS and 26 matched healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent MRI and flortaucipir-PET. The patient population included patients with primary progressive apraxia of speech (PPAOS) and non-fluent variant/agrammatic primary progressive aphasia (agPPA). Flortaucipir PET scans and DTI were coregistered using rigid registration with a mutual information cost function in subject space. Alignments between DTI and flortaucipir PET were inspected in all cases. Whole-brain tractography was calculated using deterministic algorithms by a tractography reconstruction tool (DSI-studio) and specific tracts were identified using an automatic fiber tracking atlas-based method. Fractional anisotropy (FA) and flortaucipir standardized uptake value ratios (SUVRs) were averaged across the frontal aslant tract, arcuate fasciculi, inferior frontal-occipital fasciculus, inferior and middle longitudinal fasciculi, as well as the SMA commissural fibers. Reduced FA (p < .0001) and elevated flortaucipir SUVR (p = .0012) were observed in PAOS cases compared to controls across all combined WM tracts. For flortaucipir SUVR, the greatest differentiation of PAOS from controls was achieved with the SMA commissural fibers (area under the receiver operator characteristic curve [AUROC] = 0.83), followed by the left arcuate fasciculus (AUROC = 0.75) and left frontal aslant tract (AUROC = 0.71). Our findings demonstrate that flortaucipir uptake is increased across WM tracts related to speech/language difficulties in PAOS., (© 2024 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Progressive apraxia of speech (PAOS) is a neurodegenerative motor-speech disorder that most commonly arises from a four-repeat tauopathy. Recent studies have established that progressive apraxia of speech is not a homogenous disease but rather there are distinct subtypes: the phonetic subtype is characterized by distorted sound substitutions, the prosodic subtype by slow and segmented speech and the mixed subtype by a combination of both but lack of predominance of either. There is some evidence that cross-sectional patterns of neurodegeneration differ across subtypes, although it is unknown whether longitudinal patterns of neurodegeneration differ. We examined longitudinal patterns of atrophy on MRI, hypometabolism on 18F-fluorodeoxyglucose-PET and tau uptake on flortaucipir-PET in a large cohort of subjects with PAOS that had been followed for many years. Ninety-one subjects with PAOS (51 phonetic, 40 prosodic) were recruited by the Neurodegenerative Research Group. Of these, 54 (27 phonetic, 27 prosodic) returned for annual follow-up, with up to seven longitudinal visits (total visits analysed = 217). Volumes, metabolism and flortaucipir uptake were measured for subcortical and cortical regions, for all scans. Bayesian hierarchical models were used to model longitudinal change across imaging modalities with PAOS subtypes being compared at baseline, 4 years from baseline, and in terms of rates of change. The phonetic group showed smaller volumes and worse metabolism in Broca's area and the striatum at baseline and after 4 years, and faster rates of change in these regions, compared with the prosodic group. There was also evidence of faster spread of hypometabolism and flortaucipir uptake into the temporal and parietal lobes in the phonetic group. In contrast, the prosodic group showed smaller cerebellar dentate, midbrain, substantia nigra and thalamus volumes at baseline and after 4 years, as well as faster rates of atrophy, than the phonetic group. Greater hypometabolism and flortaucipir uptake were also observed in the cerebellar dentate and substantia nigra in the prosodic group. Mixed findings were observed in the supplementary motor area and precentral cortex, with no clear differences observed across phonetic and prosodic groups. These findings support different patterns of disease spread in PAOS subtypes, with corticostriatal patterns in the phonetic subtype and brainstem and thalamic patterns in the prosodic subtype, providing insight into the pathophysiology and heterogeneity of PAOS., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Although much remains unknown about what creates risk for women's intimate partner violence (IPV) victimization across time, trauma exposure and mental health are likely contributors. Specifically, posttraumatic stress (PTS) is a risk factor for IPV victimization, yet we know less about the unique contributions of PTS symptom domains to IPV risk. Identification of PTS symptom domains that confer risk for IPV has the potential to inform novel targets of intervention., Method: This study follows women with children ( N = 118) across 8 years to identify the trauma exposure, mental health, and sociodemographic factors that contribute to IPV victimization risk using longitudinal multilevel modeling., Results: Higher levels of PTS symptoms were associated with initially greater number of IPV victimization acts experienced (i.e., "IPV victimization"). However, across time, women with higher PTS symptoms decreased more quickly in IPV victimization than those with lower PTS symptoms. Higher levels of PTS arousal and reexperiencing were each associated with initially higher levels of IPV victimization. In addition, higher levels of PTS reexperiencing and arousal remained associated with higher levels of IPV victimization across time. Women's age was inversely related to IPV victimization over time only when accounting for the PTS symptom domains., Conclusions: Findings are that collapsing PTS symptoms into an overall construct may be too imprecise to identify key mechanisms for IPV victimization risk. IPV prevention should prioritize addressing reexperiencing and arousal symptoms to curb future IPV victimization. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: Chronic health diseases such as congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM) affect 6 in 10 Americans and contribute to 90% of the $4.1 trillion health care expenditures. The objective of this study was to measure the effect of clinical video telehealth (CVT) on health care utilization and mortality. A retrospective cohort study of Veterans ≥65 years with CHF, COPD, or DM was conducted. Measures: Veterans using CVT were matched 1:3 on demographic characteristics to Veterans who did not use CVT. Outcomes included 1-year incidence of ED visits, inpatient admissions, and mortality, reported as adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: Final analytical cohorts included 22,280 Veterans with CHF, 51,872 Veterans with COPD, and 170,605 Veterans with DM. CVT utilization was associated with increased ED visits for CHF (aOR: 1.24; 95% CI: 1.15-1.34), COPD (aOR: 1.20; 95% CI: 1.14-1.26), and DM (aOR: 1.07; 95% CI: 1.00-1.10). For CHF, there was no difference between CVT utilization and inpatient admissions (aOR: 0.98; 95% CI 0.91-1.05) or mortality (aOR: 1.03; 95% CI: 0.93-1.15). For COPD, CVT was associated with increased inpatient admissions (aOR: 1.08; 95% CI: 1.02-1.13) and mortality (aOR: 1.36; 95% CI: 1.25-1.48). For DM, CVT utilization was associated with lower risk of inpatient admissions (aOR: 0.83; 95% CI: 0.80-0.86) and mortality (aOR: 0.89; 95% CI: 0.84-0.95). Conclusions: CVT use as an alternative care site might serve as an early warning system, such that this mechanism may indicate when an in-person assessment is needed for potential exacerbation of conditions. Although inpatient and mortality varied, ED utilization was higher with CVT. Exploring pathways accessing clinical care through CVT, and how CVT is directly or indirectly associated with immediate and long-term clinical outcomes would be valuable.

Pregnancy is a time of increased vulnerability to psychopathology, yet limited work has investigated the extent to which variation in psychopathology during pregnancy is shared and unshared across syndromes and symptoms. Understanding the structure of psychopathology during pregnancy, including associations with childhood experiences, may elucidate risk and resilience factors that are transdiagnostic and/or specific to particular psychopathology phenotypes. Participants were 292 pregnant individuals assessed using multiple measures of psychopathology. Confirmatory factor analyses found evidence for a structure of psychopathology consistent with the Hierarchical Taxonomy of Psychopathology (HiTOP). A common transdiagnostic factor accounted for most variation in psychopathology, and both adverse and benevolent childhood experiences (ACEs and BCEs) were associated with this transdiagnostic factor. Furthermore, pregnancy-specific anxiety symptoms most closely reflected the dimension of Fear, which may suggest shared variation with manifestations of fear that are not pregnancy-specific. ACEs and BCEs also linked to specific prenatal psychopathology involving thought problems, detachment, and internalizing, externalizing, antagonistic, and antisocial behavior. These findings extend the dimensional and hierarchical HiTOP model to pregnant individuals and show how maternal childhood risk and resilience factors relate to common and specific forms of psychopathology during pregnancy as a period of enhanced vulnerability.

Improved oocyte competence for embryo development and pregnancy was observed following ovulation of preovulatory follicles with greater physiological maturity, as indicated by estradiol production, prior to the gonadotropin-releasing hormone (GnRH)-induced luteinizing hormone (LH) surge. It was hypothesized that follicular fluid from preovulatory follicles of greater maturity better supports the maturing oocyte's metabolic requirements and improves embryo development. The objective was to determine if differences in preovulatory follicular fluid due to follicle maturity influence oocyte metabolism during in vitro maturation (IVM) and affect embryo development. Bovine preovulatory follicular fluid was collected 18 h after a GnRH-induced LH surge. Serum estradiol concentration at GnRH administration categorized follicles as greater or lesser maturity. Immature bovine oocytes were submitted to 24 h IVM in medium supplemented with 20% follicular fluid from preovulatory follicles of greater or lesser maturity. Embryo development was recorded. Oocyte maturation media and media conditioned by developing embryos were submitted for metabolomics. A randomized block design was utilized to determine differences in embryo development and media metabolites ( P ≤ 0.05). Blastocysts from oocytes matured in greater vs. lesser maturity follicular fluid had a more moderate rate of development ( P = 0.01). At the conclusion of 24 h IVM, abundance of 66 metabolites differed between greater and lesser follicle maturity treatments. Nine metabolites differed in media conditioned by developing embryos. Metabolome results suggest improved amino acid, purine, and glucose metabolism, followed by a more efficient rate of embryo development, in oocytes matured in greater vs lesser maturity follicular fluid., (© The Author(s) 2024. Published by Oxford University Press on behalf of National Academy of Sciences.)

Progressive supranuclear palsy is a neurodegenerative disease characterized by the deposition of four-repeat tau in neuronal and glial lesions in the brainstem, cerebellar, subcortical and cortical brain regions. There are varying clinical presentations of progressive supranuclear palsy with different neuroimaging signatures, presumed to be due to different topographical distributions and burden of tau. The classic Richardson syndrome presentation is considered a subcortical variant, whilst progressive supranuclear palsy with predominant speech and language impairment is considered a cortical variant, although the pathological underpinnings of these variants are unclear. In this case-control study, we aimed to determine whether patterns of regional tau pathology differed between these variants and whether tau burden correlated with neuroimaging. Thirty-three neuropathologically confirmed progressive supranuclear palsy patients with either the Richardson syndrome ( n = 17) or speech/language ( n = 16) variant and ante-mortem magnetic resonance imaging were included. Tau lesion burden was semi-quantitatively graded in cerebellar, brainstem, subcortical and cortical regions and combined to form neuronal and glial tau scores. Regional magnetic resonance imaging volumes were converted to Z -scores using 33 age- and sex-matched controls. Diffusion tensor imaging metrics, including fractional anisotropy and mean diffusivity, were calculated. Tau burden and neuroimaging metrics were compared between groups and correlated using linear regression models. Neuronal and glial tau burden were higher in motor and superior frontal cortices in the speech/language variant. In the subcortical and brainstem regions, only the glial tau burden differed, with a higher burden in globus pallidus, subthalamic nucleus, substantia nigra and red nucleus in Richardson's syndrome. No differences were observed in the cerebellar dentate and striatum. Greater volume loss was observed in the motor cortex in the speech/language variant and in the subthalamic nucleus, red nucleus and midbrain in Richardson's syndrome. Fractional anisotropy was lower in the midbrain and superior cerebellar peduncle in Richardson's syndrome. Mean diffusivity was greater in the superior frontal cortex in the speech/language variant and midbrain in Richardson's syndrome. Neuronal tau burden showed associations with volume loss, lower fractional anisotropy and higher mean diffusivity in the superior frontal cortex, although these findings did not survive correction for multiple comparisons. Results suggest that a shift in the distribution of tau, particularly neuronal tau, within the progressive supranuclear palsy network of regions is driving different clinical presentations in progressive supranuclear palsy. The possibility of different disease epicentres in these clinical variants has potential implications for the use of imaging biomarkers in progressive supranuclear palsy., Competing Interests: F.O., A.F.C., H.M.C., J.R.D., Y.C.S. and M.L.S. have nothing to disclose. J.L.W., K.A.J., C.R.J., F.Ali., H.B., M.M.M., C.G.S., D.W.D. and R.L.U. receive support from the US NIH. K.A.J. is an Associate Editor of Annals of Clinical and Translation Neurology. F.Agosta. is an Associate Editor of NeuroImage: Clinical, has received speaker honoraria from Biogen Idec and Roche and receives or has received research supports from the Italian Ministry of Health, AriSLA (Fondazione Italiana di Ricerca per la SLA), the European Research Council and Foundation Research on Alzheimer Disease. M.F. is Editor-in-Chief of the Journal of Neurology and Associate Editor of Human Brain Mapping, received compensation for consulting services and/or speaking activities from Almiral, Alexion, Bayer, Biogen, Celgene, Eli Lilly, Genzyme, Merck Serono, Novartis, Roche, Sanofi, Takeda and Teva Pharmaceutical Industries and receives research support from Biogen Idec, Merck Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla and ARiSLA (Fondazione Italiana di Ricerca per la SLA)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Purpose: The purpose of this study was to examine whether differences in motor speech features are related to presentations of dysphagia in progressive supranuclear palsy (PSP) given the sparsity of data examining this relationship., Method: Motor speech disorder (MSD) type and severity along with specific swallowing variables were analysed to obtain insights among these relationships in 73 participants with PSP., Result: Results revealed that most participants (93%) had dysarthria, with 19% having co-occurring apraxia of speech (AOS). Greater MSD severity was related to more severe pharyngeal phase impairments (95% CI [-0.917, -0.146], p  = 0.008). While certain motor speech and swallowing scores varied minimally across participants, incremental changes in these functions were more likely to occur when specific MSD features were present. A trend for participants with spastic dysarthria and/or AOS to exhibit more severe dysphagia was observed., Conclusion: This study points to the need for thorough neurological evaluation, with inclusion of speech-language pathology consultation, in the standard of care for PSP. Comprehensive assessment of both motor speech and swallowing functions can inform differential diagnosis and assist patients/families facing decisions regarding modalities for communication and nutrition in the setting of neurodegenerative disease. Additional research may yield greater insights about relevant assessment and intervention considerations in PSP.

Two variants of semantic dementia are recognized based on the laterality of temporal lobe involvement: a left-predominant variant associated with verbal knowledge impairment and a right-predominant variant associated with behavioural changes and non-verbal knowledge loss. This cross-sectional clinicoradiologic study aimed to assess whole hippocampal, subregion, and/or subfield volume loss in semantic dementia versus controls and across its variants. Thirty-five semantic dementia participants and 15 controls from the Neurodegenerative Research Group at Mayo Clinic who had completed 3.0-T volumetric magnetic resonance imaging and 18 F-fluorodeoxyglucose-positron emission tomography were included. Classification as left-predominant ( n = 25) or right-predominant ( n = 10) variant was based on temporal lobe hypometabolism. Volumes of hippocampal subregions (head, body, and tail) and subfields (parasubiculum, presubiculum, subiculum, cornu ammonis 1, cornu ammonis 3, cornu ammonis 4, dentate gyrus, molecular layer, hippocampal-amygdaloid transition area, and fimbria) were obtained using FreeSurfer 7. Subfield volumes were measured separately from head and body subregions. We fit linear mixed-effects models using log-transformed whole hippocampal/subregion/subfield volumes as dependent variables; age, sex, total intracranial volume, hemisphere and a group-by-hemisphere interaction as fixed effects; and subregion/subfield nested within hemisphere as a random effect. Significant results ( P < 0.05) are hereby reported. At the whole hippocampal level, the dominant (predominantly involved) hemisphere of both variants showed 23-27% smaller volumes than controls. The non-dominant (less involved) hemisphere of the right-predominant variant also showed volume loss versus controls and the left-predominant variant. At the subregional level, both variants showed 17-28% smaller dominant hemisphere head, body, and tail than controls, with the right-predominant variant also showing 8-12% smaller non-dominant hemisphere head than controls and left-predominant variant. At the subfield level, the left-predominant variant showed 12-36% smaller volumes across all dominant hemisphere subfields and 14-15% smaller non-dominant hemisphere parasubiculum, presubiculum (head and body), subiculum (head) and hippocampal-amygdaloid transition area than controls. The right-predominant variant showed 16-49% smaller volumes across all dominant hemisphere subfields and 14-22% smaller parasubiculum, presubiculum, subiculum, cornu ammonis 3, hippocampal-amygdaloid transition area (all from the head) and fimbria of non-dominant hemisphere versus controls. Comparison of dominant hemispheres showed 16-29% smaller volumes of the parasubiculum, presubiculum (head) and fimbria in the right-predominant than left-predominant variant; comparison of non-dominant hemispheres showed 12-15% smaller cornu ammonis 3, cornu ammonis 4, dentate gyrus, hippocampal-amygdaloid transition area (all from the head) and cornu ammonis 1, cornu ammonis 3 and cornu ammonis 4 (all from the body) in the right-predominant variant. All hippocampal subregion/subfield volumes are affected in semantic dementia, although some are more affected in both dominant and non-dominant hemispheres of the right-predominant than the left-predominant variant by the time of presentation. Involvement of hippocampal structures is apparently more subregion dependent than subfield dependent, indicating possible superiority of subregion volumes as disease biomarkers., Competing Interests: A.F.C., S.D.W. and N.T.T.P. have nothing to disclose. J.R.D., H.M.C., R.L.U., M.M.M., H.B., V.J.L., C.G.S., J.L.W. and K.A.J. receive research support from the US NIH. K.A.J. is an Associate Editor for the Annals of Clinical and Translational Neurology., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Objectives: 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., Methods: 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., Results: 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., Discussion: 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., Competing Interests: G. Meade receives support from the NIH; J.L. Whitwell receives support from the NIH; D.W. Dickson receives support from the NIH; J.R. Duffy receives support from the NIH; H.M. Clark receives support from the NIH; J.E. Ahlskog reports no disclosures relevant to the manuscript; M.M. Machulda receives support from the NIH; K.A. Josephs receives support from the NIH; R.L. Utianski receives support from the NIH. Go to Neurology.org/NG for full disclosures., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Purpose: 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., Method: 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., Results: 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., Conclusions: 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.

Introduction: Progressive supranuclear palsy (PSP) is an atypical parkinsonism caused by the intracerebral aggregation of the microtubule-associated protein tau (MAPT) which is encoded by MAPT gene. Although PSP is a sporadic disease, MAPT mutations have been reported in rare cases., Methods: Among 190 patients with PSP who were recruited by the Neurodegenerative Research Group at Mayo Clinic during 2009-2023, we identified two patients who fulfilled diagnostic criteria for PSP-Richardson's syndrome (PSP-RS) and harbor novel MAPT mutations. To better investigate the potential effects of these mutations, we compared the clinical, and neuroimaging characteristics of these two patients to 20 randomly selected patients with PSP-RS without a MAPT mutation., Results: MAPT c.1024G > A, p. Glu342Lys, and MAPT c.1217 G > A, p. Arg406Gln mutations were found in 2 men who developed PSP-RS with atypical features at the ages of 60 and 62 years, respectively. Glu342Lys mutation was associated with features resembling alpha-synucleinopathies (autonomic dysfunction, dream enactment behavior), while both mutations were associated with features suggestive of Alzheimer's disease with poorer performance on tests of episodic memory. Comparison of 18 F-flortaucipir uptake between the two MAPT mutation cases with 20 patients without a mutation revealed increased signal on flortaucipir-PET in bilateral medial temporal lobe regions (amygdala, entorhinal cortices, hippocampus, parahippocampus) but not in PSP-related regions (globus pallidum, midbrain, superior frontal cortex and dentate nucleus of the cerebellum)., Conclusion: Glu342Lys and Arg406Gln mutations appear to modify the PSP-RS phenotype by targeting the medial temporal lobe regions resulting in more memory loss and greater flortaucipir uptake., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Two subtypes of progressive apraxia of speech (PAOS) have been recognized: phonetic PAOS (PAOS&#95;ph) where speech output is dominated by distorted sound substitutions and prosodic PAOS (PAOS&#95;pr) which is dominated by segmented speech. We investigate whether these PAOS subtypes have different white matter microstructural abnormalities measured by diffusion tensor tractography. Thirty-three patients with PAOS (21 PAOS&#95;ph and 12 PAOS&#95;pr) and 19 healthy controls were recruited by the Neurodegenerative Research Group (NRG) and underwent diffusion MRI. Using a whole-brain tractography approach, fractional anisotropy (FA) and mean diffusivity (MD) were extracted for cortico-cortical, cortico-subcortical, cortical-projection, and cerebello-cortical white matter tracts. A hierarchical linear model was applied to assess tract-level FA and MD across groups. Both PAOS&#95;ph and PAOS&#95;pr showed degeneration of cortico-cortical, cortico-subcortical, cortical-projection, and cerebello-cortical white matter tracts compared to controls. However, degeneration of the body of corpus callosum, superior thalamic radiation, and superior cerebellar peduncle was greater in PAOS&#95;pr compared to PAOS&#95;ph, and degeneration of the inferior segment of the superior longitudinal fasciculus (SLF) was greater in PAOS&#95;ph compared to PAOS&#95;pr. Worse parkinsonism correlated with greater degeneration of cortico-cortical and cortico-subcortical tracts in PAOS&#95;ph. Apraxia of speech articulatory error score correlated with degeneration of the superior cerebellar peduncle tracts in PAOS&#95;pr. Phonetic and prosodic PAOS involve the compromise of a similar network of tracts, although there are connectivity differences between types. Whereas clinical parameters are the current gold standard to distinguish PAOS subtypes, our results allege the use of DTI-based tractography as a supplementary method to investigate such variants., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest. All procedures performed in this study were approved by and conducted following the ethical standards of the institutional human research ethics committee. In doing so, they were performed according to the standards of the 1964 Helsinki Declaration and its later amendments or comparable standards. Informed consent was obtained from all individual participants included in this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Primary progressive aphasia (PPA) variants present with distinct disruptions in speech-language functions with little known about the interplay between affected and spared regions within the speech-language network and their interaction with other functional networks. The Neurodegenerative Research Group, Mayo Clinic, recruited 123 patients with PPA (55 logopenic (lvPPA), 44 non-fluent (nfvPPA) and 24 semantic (svPPA)) who were matched to 60 healthy controls. We investigated functional connectivity disruptions between regions within the left-speech-language network (Broca, Wernicke, anterior middle temporal gyrus (aMTG), supplementary motor area (SMA), planum temporale (PT) and parietal operculum (PO)), and disruptions to other networks (visual association, dorsal-attention, frontoparietal and default mode networks (DMN)). Within the speech-language network, multivariate linear regression models showed reduced aMTG-Broca connectivity in all variants, with lvPPA and nfvPPA findings remaining significant after Bonferroni correction. Additional loss in Wernicke-Broca connectivity in nfvPPA, Wernicke-PT connectivity in lvPPA and greater aMTG-PT connectivity in svPPA were also noted. Between-network connectivity findings in all variants showed reduced aMTG-DMN and increased aMTG-dorsal-attention connectivity, with additional disruptions between aMTG-visual association in both lvPPA and svPPA, aMTG-frontoparietal in lvPPA, and Wernicke-DMN breakdown in svPPA. These findings suggest that aMTG connectivity breakdown is a shared feature in all PPA variants, with lvPPA showing more extensive connectivity disruptions with other networks., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Singh has no disclosures to report. Drs. Whitwell, Botha, Utianski, Clark, Duffy, Machulda, Schwarz, Lowe and Josephs reported receiving research funding from the NIH. Dr. Graff-Radford reported receiving research support from the NIH and DSMB for StrokeNET. He is an investigator in a trial sponsored by USC and EISAI. Dr. Jack receives no personal compensation from any commercial entity and has no conflicts. He receives research support from NIH, the GHR foundation and the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Progressive apraxia of speech (PAOS) is characterized by difficulties with motor speech programming and planning. PAOS targets gray matter (GM) and white matter (WM) microstructure that can be assessed using diffusion tensor imaging (DTI) and multishell applications, such as neurite orientation dispersion and density imaging (NODDI). In this study, we aimed to apply DTI and NODDI to add further insight into PAOS tissue microstructure., Methods: Twenty-two PAOS patients and 26 age- and sex-matched controls, recruited by the Neurodegenerative Research Group (NRG) at Mayo Clinic, underwent diffusion MRI on 3T MRI. Brain maps of fractional anisotropy (FA) and mean diffusivity (MD) from DTI and intracellular volume fraction (ICVF) and isotropic volume fraction (IsoVF) from NODDI were generated. Global WM and GM, and specific WM tracts were identified using tractography and lobar GM regions., Results: Global WM differences between PAOS and controls were greatest for ICVF, and global GM differences were greatest for MD and IsoVF. Abnormalities in key WM tracts involved in PAOS, including the body of the corpus callosum and frontal aslant tract, were identified with FA, MD, and ICVF, with excellent differentiation of PAOS from controls (area under the receiver operating characteristic curves >.90). MD and ICVF identified abnormalities in arcuate fasciculus, thalamic radiations, and corticostriatal tracts. Significant correlations were identified between an index of articulatory errors and DTI and NODDI metrics from the arcuate fasciculus, frontal aslant tract, and inferior longitudinal fasciculus., Conclusions: DTI and NODDI represent different aspects of brain tissue microstructure, increasing the number of potential biomarkers for PAOS., (© 2024 The Authors. Brain and Behavior published by Wiley Periodicals LLC.)

Background: The high prevalence of chronic diseases, including congestive heart failure (CHF), chronic obstructive pulmonary disease (COPD), and diabetes mellitus (DM), accounts for a large burden of cost and poor health outcomes in US hospitals, and home telehealth (HT) monitoring has been proposed to improve outcomes., Objective: To measure the association between HT initiation and 12-month inpatient hospitalizations, emergency department (ED) visits, and mortality in veterans with CHF, COPD, or DM., Design: Comparative effectiveness matched cohort study., Patients: Veterans aged 65 years and older treated for CHF, COPD, or DM., Main Measures: We matched veterans initiating HT with veterans with similar demographics who did not use HT (1:3). Our outcome measures included a 12-month risk of inpatient hospitalization, ED visits, and all-cause mortality., Key Results: A total of 139,790 veterans with CHF, 65,966 with COPD, and 192,633 with DM were included in this study. In the year after HT initiation, the risk of hospitalization was not different in those with CHF (adjusted odds ratio [aOR] 1.01, 95% confidence interval [95%CI] 0.98-1.05) or DM (aOR 1.00, 95%CI 0.97-1.03), but it was higher in those with COPD (aOR 1.15, 95%CI 1.09-1.21). The risk of ED visits was higher among HT users with CHF (aOR 1.09, 95%CI 1.05-1.13), COPD (1.24, 95%CI 1.18-1.31), and DM (aOR 1.03, 95%CI 1.00-1.06). All-cause 12-month mortality was lower in those initiating HT monitoring with CHF (aOR 0.70, 95%CI 0.67-0.73) and DM (aOR 0.79, 95%CI 0.75-0.83), but higher in COPD (aOR 1.08, 95%CI 1.00-1.16)., Conclusions: The initiation of HT was associated with increased ED visits, no change in hospitalizations, and lower all-cause mortality in patients with CHF or DM, while those with COPD had both higher healthcare utilization and all-cause mortality., (© 2023. The Author(s), under exclusive licence to Society of General Internal Medicine.)

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., (© 2023. The Author(s).)

Most recent studies of progressive apraxia of speech (PAOS) have focused on patients with phonetic or prosodic predominant PAOS to understand the implications of the presenting clinical phenotype. Patients without a clearly predominating speech quality, or mixed AOS, have been excluded. Given the implications for disease progression, it is important to understand these patients early in the disease course to inform appropriate education and prognostication. The aim of this study was to describe a cohort of ten patients with initially mixed PAOS and how their clinical course evolves. Four patients were rated prosodic predominant later on (mild AOS at first visit); five were later designated phonetic (four with more than mild AOS at first visit); one was judged mixed at all visits. The study suggests patients without a clear predominance of speech featuresshould still be included in PAOS studies and thought of on the continuum of the disease spectrum., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Prior studies have shown that communication-related participation restrictions in patients with degenerative disease do not always match clinician judgment or objective indices of symptom severity. Although there is a growing body of literature documenting that discrepancies between patients with dementia and their care partners' perception of participation restrictions exist, it is not known how care partner perceptions of communication participation restrictions specifically match or diverge from the patients' experiences, which may inform the use of care partner proxy in the context of degenerative diseases., Method: Thirty-eight patients with progressive neurologic conditions (progressive supranuclear palsy, corticobasal syndrome, and primary progressive aphasia or apraxia of speech) and, in most instances, focal cognitive-communication disorders were included. The patients and their accompanying care partners independently completed the Communicative Participation Item Bank, short form, a 10-question survey about communication participation restrictions in different contexts. Care partners were instructed to complete the form with their perception of the patient's experience. The difference between patient and care partner total scores were calculated and analyzed relative to clinical and demographic variables of interest., Results: Care partner ratings modestly tracked with patient experience and objective indices of symptom severity but did not exactly match patient ratings. The presence of aphasia increased, but did not fully account for, the likelihood of a discrepancy between care partner and patient ratings., Conclusion: Although careful consideration should be given prior to using care-partner report as a proxy for patient experience, it is worthwhile to include care partner ratings as a means of supporting conversations about differing perceptions, guiding joint intervention planning, and monitoring care-partner perceptions of change along with the implementation of supported conversation strategies.

Purpose: The purpose of this study was to describe, compare, and understand speech modulation capabilities of patients with varying motor speech disorders (MSDs) in a paradigm in which patients made highly cued attempts to speak faster or slower., Method: Twenty-nine patients, 12 with apraxia of speech (AOS; four phonetic and eight prosodic subtype), eight with dysarthria (six hypokinetic and two spastic subtype), and nine patients without any neurogenic MSD completed a standard motor speech evaluation where they were asked to repeat words and sentences, which served as their "natural" speaking rate. They were then asked to repeat lower complexity (counting 1-5; repeating "cat" and "catnip" 3 times each) and higher complexity stimuli (repeating "catastrophe" and "stethoscope" 3 times each and "My physician wrote out a prescription" once) as fast/slow as possible. Word durations and interword intervals were measured. Linear mixed-effects models were used to assess differences related to MSD subtype and stimuli complexity on bidirectional rate modulation capacity as indexed by word duration and interword interval. Articulatory accuracy was also judged and compared., Results: Patients with prosodic AOS demonstrated a reduced ability to go faster; while they performed similarly to patients with spastic dysarthria when counting, patients with spastic dysarthria were able to increase rate similar to controls during sentence repetition; patients with prosodic AOS could not and made increased articulatory errors attempting to increase rate. AOS patients made more articulatory errors relative to other groups, regardless of condition; however, their percentage of errors reduced with an intentionally slowed speaking rate., Conclusions: The findings suggest comparative rate modulation abilities in conjunction with their impact on articulatory accuracy may support differential diagnosis between healthy and abnormal speech and among subtypes of MSDs (i.e., type of dysarthria or AOS). Findings need to be validated in a larger, more representative cohort encompassing several types of MSDs., Supplemental Material: https://doi.org/10.23641/asha.22044632.

Adaptation to intimate partner violence (IPV) exposure involves alterations in transdiagnostic processes including effortful control (EC), and yet little attention has been given to the ways such processes interact with family-level factors, such as caregivers' psychopathology. This study used latent change score modeling to compare trajectories of EC and caregivers' depressive (CD) symptoms between children and adolescents ( N = 365) ages 7-17 who had witnessed IPV (IPV+; 45.3%) and those who had not (IPV-) across 3 years. Findings suggested that IPV exposure moderated relationships between EC and CD. CD was higher and EC was lower for IPV+ relative to IPV- participants, although there was significant variation around mean-level CD and EC in both groups. CD and EC were only linked for IPV+ participants, where higher baseline CD was associated with lower EC that lagged behind IPV- participants' EC across the 3 years of the study. Rates of change for CD significantly varied for the IPV+ group only, indicating that individual difference factors interacted with IPV exposure to influence changes in CD. These findings inform literature on transdiagnostic adaptation processes and point to the potential utility of interventions to reduce IPV and CD in supporting EC in children and adolescents across contexts.

Purpose: To describe qualitative and quantitative longitudinal changes in dopamine transporter uptake (DaT) scan findings in progressive apraxia of speech (PAOS) patients., Methods: DaTQUANT software was used to quantify uptake in the left and right caudate and putamen in DaT scans of 39 patients with PAOS, 19 with repeat scans. Clinical radiologic impressions were used as the gold standard for evaluating whether quantitative measures (z-score of left and right putamen and caudate uptake) aligned with gestalt impressions of DaT abnormalities and clinical impairments, cross-sectionally. Measures at first and last available DaT were used to evaluate change over time and the influence of qualitative abnormality at first visit on change over time., Results: Cross-sectionally, 16/39 patients had abnormal DaT scans on visual read, with differences in all quantitative DaT measures between those with (ab)normal scans, but without differences in any clinical measures (apraxia of speech, aphasia, or parkinsonism). Three patients that had normal DaT scans at baseline were read as abnormal at subsequent visits, with coinciding change in quantitative measures. At the group level, across the 19 patients with repeat imaging, no statistical change in left or right caudate or putamen scores was observed despite progression of clinical indices. Abnormality at first visit did not statistically influence the rate of change over time, although trends were observed., Conclusions: Approximately 40-50% of patients with PAOS have or will develop DaT scans that may be visually read as abnormal. Quantitative measures of DaT match visual reads cross-sectionally, but may not map to clinical progression, including of parkinsonism, observed in these patients., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Author(s).)

Introduction: Preovulatory follicle response to the luteinizing hormone (LH) surge leads to metabolic, molecular, and functional changes in the oocyte and somatic follicular cells from the onset of estrus to ovulation. Follicular fluid contains metabolites, miRNAs, proteins, and hormones that are byproducts of follicular metabolism and support cellular processes of oocyte, cumulus, and granulosa constituents. Numerous studies have highlighted the importance of follicular fluid composition to support fertility, but critical gaps exist toward understanding dynamic modifications in the follicular fluid metabolome from estrous onset to ovulation. The hypothesis was that abundance of follicular fluid metabolites is dependent on follicle progression post LH surge and variability in follicular fluid metabolome profiles indicate key processes required for preparation of the follicle and oocyte for optimal fertility. The objective was to generate preovulatory follicular fluid metabolome profiles and discern differences in the metabolome of preovulatory follicular fluid samples collected at onset of estrus, 11 h post estrous onset, and 18 h post estrous onset. Methods: Estrus was synchronized in non-lactating Jersey cows (n=40) and follicular fluid was collected immediately after the first observed standing mount (hr 0) or at approximately h 11 or 18 after the first standing mount. Ultra-High-Performance Liquid Chromatography-High Resolution Mass Spectrometry was performed on preovulatory follicular fluid samples ( n = 9 collected at hr 0, 9 at h 11, and 10 at h 18) and a multiple linear model was performed to determine if time post estrous onset impacted metabolite abundance. Results: Metabolites influenced by time post estrous onset were tested for enrichment in KEGG pathways. Ninety metabolites were identified in follicular fluid samples. Twenty metabolites differed in abundance among timepoints post estrous onset ( p ≤ 0.05). Pathways corresponding to amino acid and energy metabolism were enriched with metabolites impacted by time post estrous onset (FDR ≤ 0.10). Discussion: Results from the current study indicate early response to the LH surge to increase bioavailability of amino acids and metabolites used by the cumulus and granulosa cells for energy production and shuttled into the oocyte to support meiotic maturation. Such metabolites may later be used by the ovulatory follicle for protein production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hessock, Edwards, Schrick, Payton, Campagna, Pollock, Clark, Stokes, Klabnik, Hill, Roberts, Hinson and Moorey.)

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.

Childhood exposure to intimate partner violence (IPV) can have lasting effects on well-being. Children also display resilience following IPV exposure. Yet, little research has prospectively followed changes in both maladaptive and adaptive outcomes in children who experience IPV in early life. The goal of the current study was to investigate how child factors (irritability), trauma history (severity of IPV exposure), maternal factors (mental health, parenting), and early intervention relate to trajectories of behavior problems (internalizing and externalizing problems) and resilience (prosocial behavior, emotion regulation), over 8 years. One hundred twenty mother-child dyads participated in a community-based randomized controlled trial of an intervention for IPV-exposed children and their mothers. Families completed follow-up assessments 6-8 months ( N = 71) and 6-8 years ( N = 68) later. Although intention-to-treat analyses did not reveal significant intervention effects, per-protocol analyses suggested that participants receiving an effective dose (eight sessions) of the treatment had fewer internalizing problems over time. Child irritability and maternal parenting were associated with both behavior problems and resilience. Maternal mental health was uniquely associated with child behavior problems, whereas maternal positive parenting was uniquely associated with child resilience. Results support the need for a dyadic perspective on child adjustment following IPV exposure.

Introduction: In the context of Alzheimer's disease phenotypes, patients may present with symptoms and signs that do not exclusively fit into one of the existing phenotypic categories, which often delays timely diagnosis and initiation of services to optimize patient awareness and coping., Case Report: A 74-year-old woman presented with the complaint of progressive word-finding difficulty, raising our suspicion for primary progressive aphasia. Clinical evaluations, however, also revealed emerging cortical visual deficits consistent with posterior cortical atrophy. During evaluation 1 year later, Gerstmann syndrome was evident. Her in vivo neuroimaging was positive for beta-amyloid and tau biomarkers of Alzheimer's disease pathology., Conclusion: In addition to contributing to the literature on the heterogeneity of the clinical manifestations of Alzheimer's disease, this report highlights that a breakdown in the visual-lexical interface can account for anomia in posterior cortical atrophy at least in some cases. Other relevant clinical insights pertinent to this case are discussed., Competing Interests: V.J.L. consults for Bayer Schering Pharma, Piramal Life Sciences, Life Molecular Imaging, Eisai Inc., AVID Radiopharmaceuticals, and Merck Research and receives research support from GE Healthcare, Siemens Molecular Imaging, AVID Radiopharmaceuticals and the NIH (NIA, NCI). The remaining authors declare no conflict of interest for this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Aims: We aimed to summarise the existing literature on insulin dose titration in gestation diabetes., Methods: Databases: Medline, EMBASE, CENTRAL and CINAHL were systematically searched for trials and observational studies comparing insulin titration strategies in gestational diabetes., Results: No trials comparing insulin dose titration strategies were identified. Only one small (n = 111) observational study was included. In this study, patient-led daily basal insulin titration was associated with higher insulin doses, tighter glycaemic control, and lower birthweight, vs weekly clinician-led titration., Conclusions: There is a paucity of evidence to support optimal insulin titration in gestational diabetes. Randomized trials are required., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The purpose of this study was to examine the interrater reliability and validity of the Apraxia of Speech Rating Scale (ASRS-3.5) as an index of the presence and severity of apraxia of speech (AOS) and the prominence of several of its important features., Method: Interrater reliability was assessed for 27 participants. Validity was examined in a cohort of 308 participants (120 with and 188 without progressive AOS) through item analysis; item-Total score correlations; correlations among ASRS Total score and component subscores and independent clinical ratings of AOS, dysarthria and aphasia severity, intelligibility, and articulatory errors, as well as years postonset and age; and regression models assessing item and Total score prediction of AOS presence., Results: Interrater reliability was good or excellent for most items and excellent for the Total score. Item and Total score analyses revealed good separation of participants with versus without AOS. Inter-item and item-Total score correlations were generally moderately high as were correlations between the ASRS Total score and independent ratings of AOS severity, intelligibility, and articulatory errors. The Total score was not meaningfully correlated with ratings of aphasia and dysarthria severity, years postonset, or age. Total scores below 7 and above 10 revealed excellent diagnostic sensitivity and specificity for AOS. The presence of eight or more abnormal features was also highly predictive of AOS presence., Conclusions: The ASRS-3.5 is a reliable and valid scale for identifying the presence and severity of AOS and its predominant features. It has excellent sensitivity to AOS presence and excellent specificity relative to aphasia and dysarthria in patients with neurodegenerative disease., Supplemental Material: https://doi.org/10.23641/asha.21817584.

Introduction: Progressive supranuclear palsy (PSP) is associated with several clinical variants defined based on ocular motor dysfunction, postural instability, akinesia, and cognitive dysfunction, although little is known about how these features progress over time. We aimed to assess the evolution of these core clinical features across variants and assess baseline clinical and neuroimaging predictors of progression., Methods: Ninety-three PSP patients were recruited by the Neurodegenerative Research Group, Mayo Clinic, and underwent two visits 1-year apart, with baseline MRI and [ 18 F]flortaucipir PET. We compared baseline and annualized rates of clinical change on the PSP Rating Scale (total, ocular motor, gait/midline scores) and Montreal Cognitive Assessment, across PSP-Richardson's, PSP-Cortical and PSP-Subcortical variants and assessed relationships between rates of change and baseline regional imaging., Results: Ocular motor scores differed across groups at baseline and follow-up, with lowest scores observed in PSP-subcortical, but no differences were observed in rate of change across groups. PSP Rating Scale total and gait/midline scores differed across groups at follow-up and in rates of change, with PSP-subcortical showing the least impairment and slowest progression. Greatest cognitive impairment was observed in PSP-Cortical. Sample size estimates for treatment trials differed across PSP variants. Greater baseline flortaucipir uptake, but not volume, of midbrain and motor cortex correlated with faster rates of clinical decline., Conclusion: The PSP Rating Scale and its subscores might be useful markers for the prognostic stratification of PSP variants. Flortaucipir imaging at baseline may help predict rate of decline., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Purpose: Progressive apraxia of speech (PAOS) is a neurodegenerative disorder affecting the planning or programming of speech. Little is known about its magnetic susceptibility profiles indicative of biological processes such as iron deposition and demyelination. This study aims to clarify (1) the pattern of susceptibility in PAOS patients, (2) the susceptibility differences between the phonetic (characterized by predominance of distorted sound substitutions and additions) and prosodic (characterized by predominance of slow speech rate and segmentation) subtypes of PAOS, and (3) the relationships between susceptibility and symptom severity., Methods: Twenty patients with PAOS (nine phonetic and eleven prosodic subtypes) were prospectively recruited and underwent a 3 Tesla MRI scan. They also underwent detailed speech, language, and neurological evaluations. Quantitative susceptibility maps (QSM) were reconstructed from multi-echo gradient echo MRI images. Region of interest analysis was conducted to estimate susceptibility coefficients in several subcortical and frontal regions. We compared susceptibility values between PAOS and an age-matched control group and performed a correlation analysis between susceptibilities and an apraxia of speech rating scale (ASRS) phonetic and prosodic feature ratings., Results: The magnetic susceptibility of PAOS was statistically greater than that of controls in subcortical regions (left putamen, left red nucleus, and right dentate nucleus) (p < 0.01, also survived FDR correction) and in the left white-matter precentral gyrus (p < 0.05, but not survived FDR correction). The prosodic patients showed greater susceptibilities than controls in these subcortical and precentral regions. The susceptibility in the left red nucleus and in the left precentral gyrus correlated with the prosodic sub-score of the ASRS., Conclusion: Magnetic susceptibility in PAOS patients was greater than controls mainly in the subcortical regions. While larger samples are needed before QSM is considered ready for clinical differential diagnosis, the present study contributes to our understanding of magnetic susceptibility changes and the pathophysiology of PAOS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)