Explore the vast range of titles available.

Key Points Primary progressive aphasia (PPA) is a clinical syndrome caused by selective neurodegeneration of the language-dominant cerebral hemisphere, thus affecting the language network The language disorder manifest in patients with PPA can take the form of agrammatic, logopenic or semantic aphasia, depending on the anatomical distribution of cortical atrophy PPA can be caused by several types of neuropathology, including Alzheimer disease and frontotemporal lobar degeneration; these diseases tend to be associated with specific variants of PPA Concepts relating to Wernicke's area and anterior temporal lobe function need to be revised on the basis of the relationships identified between the clinical characteristics and neuroanatomy of peak atrophy sites in PPA PPA susceptibility, aetiology and pathogenesis, and the asymmetry of cerebral atrophy in particular, are poorly understood and require further elucidation Effective PPA treatments are urgently needed; development of such treatments should be considered a research area of importance Primary progressive aphasia (PPA) is caused by asymmetric, selective neurodegeneration of cerebral areas involved in language. Agrammatic and semantic PPAs are typically manifestations of frontotemporal lobar degeneration, whereas the logopenic PPA is more often associated with Alzheimer disease pathology. Here, Mesulam et al . review the subclassification, clinical features and neuropathology of PPA, and discuss how increased knowledge of PPA has advanced our understanding of the neural substrates of the language network. Primary progressive aphasia (PPA) is caused by selective neurodegeneration of the language-dominant cerebral hemisphere; a language deficit initially arises as the only consequential impairment and remains predominant throughout most of the course of the disease. Agrammatic, logopenic and semantic subtypes, each reflecting a characteristic pattern of language impairment and corresponding anatomical distribution of cortical atrophy, represent the most frequent presentations of PPA. Such associations between clinical features and the sites of atrophy have provided new insights into the neurology of fluency, grammar, word retrieval, and word comprehension, and have necessitated modification of concepts related to the functions of the anterior temporal lobe and Wernicke's area. The underlying neuropathology of PPA is, most commonly, frontotemporal lobar degeneration in the agrammatic and semantic forms, and Alzheimer disease (AD) pathology in the logopenic form; the AD pathology often displays atypical and asymmetrical anatomical features consistent with the aphasic phenotype. The PPA syndrome reflects complex interactions between disease-specific neuropathological features and patient-specific vulnerability. A better understanding of these interactions might help us to elucidate the biology of the language network and the principles of selective vulnerability in neurodegenerative diseases. We review these aspects of PPA, focusing on advances in our understanding of the clinical features and neuropathology of PPA and what they have taught us about the neural substrates of the language network.

Abstract Four right-handed patients who presented with an isolated impairment of speech or language had transactive response DNA-binding protein of 43 kDa (TDP-43) type B pathology. Comportment and pyramidal motor function were preserved at presentation. Three of the cases developed axial rigidity and oculomotor findings late in their course with no additional pyramidal or lower motor neuron impairments. However, in all 4 cases, postmortem examination disclosed some degree of upper and lower motor neuron disease (MND) pathology in motor cortex, brainstem, and spinal cord. Although TDP-43 type B pathology is commonly associated with MND and behavioral variant frontotemporal dementia, it is less recognized as a pathologic correlate of primary progressive aphasia and/or apraxia of speech as the presenting syndrome. These cases, taken together, contribute to the growing heterogeneity in clinical presentations associated with TDP pathology. Additionally, 2 cases demonstrated left anterior temporal lobe atrophy but without word comprehension impairments, shedding light on the relevance of the left temporal tip for single-word comprehension.

: SuperAgers are adults age 80+ with episodic memory performance that is as good as that of average middle-aged adults. Understanding the biological determinants of SuperAging may have relevance to preventing age-related cognitive decline and dementia. This study aimed to identify associations between genetic variations and the SuperAging phenotype using Whole Exome Sequencing (WES). : Sequence Kernel Association Combined (SKAT-C) test was conducted at the gene level including both rare and common variants in 56 SuperAgers and 22 cognitively-average controls from the Alzheimer's disease Neuroimaging Initiative (ADNI). : The SuperAging phenotype was associated with variants in the Mitogen-Activated Protein Kinase Kinase 3 gene. Three single nucleotide polymorphisms (SNPs) contributed to the significance (rs2363221 [intron 1], rs2230435 [exon 5], rs736103 [intron 7]). : MAP2K3 resides in a biological pathway linked to memory. It is in a signaling cascade associated with beta-amyloid mediated apoptosis and has enriched expression in microglia. This preliminary work suggests MAP2K3 may represent a novel therapeutic target for age-related memory decline and perhaps Alzheimer's disease (AD).

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 DesignScale or the Physiotherapy Evidence Database – PsycBITERating 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.

Wearable technologies provide continuous, real-world data on mobility, cognition, and health behaviours, creating new opportunities to support aging individuals, including those with mild cognitive impairment (MCI), Alzheimer's disease, and related dementias (ADRD). Translating insights derived from wearables into meaningful, personalized feedback can foster sustained behaviour change and enhance adherence in clinical trials and observational studies. Through a multidisciplinary lens, this session will illustrate the challenges and opportunities associated with delivering personalized feedback from wearables, specifically focusing on the following topics: 1) co-design of feedback mechanisms from wearables to improve adherence and study retention in dementia and aging research, 2) strategies for integrating multimodal sensor data into personalized interventions that drive meaningful behaviour change, and 3) lessons learned from real-world implementations in clinical trials and longitudinal studies. Lessons drawn from wearable-based clinical trials and observational studies in aging and ADRDs, including the Ontario Neurodegenerative Disease Research Initiative, the Communication Bridge Trials and the SuperAging Research Initiative, illustrate effective co-design processes for delivering personalized feedback to individuals with cognitive impairment. Recent findings from the Health in Aging, Neurodegenerative Diseases, and Dementias in Ontario study demonstrate the types and mechanisms of health behaviour changes resulting from wearable-sensor-derived personalized feedback. These studies highlight how tailored feedback can influence health behaviour changes, retention, and adherence. Challenges faced when generating and delivering personalized feedback include ensuring it remains valuable and understandable for individuals with cognitive difficulties, balancing comprehensive data collection with participant-friendly feedback approaches, and providing sufficient data fidelity for reliable and valid feedback. This session will outline practical strategies for overcoming these challenges, including evidence-based behavioural feedback models, best practices for co-designing interventions with patients, care partners, and clinicians, incorporating outcomes with high interpretability, and transparent analytics pipelines featuring sensor interoperability. By integrating personalized feedback from wearable sensors into dementia and aging research, we can enhance health behaviours, improve participant retention, and maximize the effectiveness of clinical trials and observational studies. This session will offer a scientific and practical framework for utilizing wearable technology to foster engagement, facilitate behaviour change, and enhance health outcomes in older adults and those with ADRD.

Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized by progressive language decline. Access to care for individuals living with PPA is limited by a shortage of evidence-based interventions and qualified clinicians. While technology-supported approaches show promise in improving access to care, there has been no systematic exploration of the factors affecting web application use in this population. This study evaluated the usage and feasibility of an app-based intervention through quantitative application engagement data and qualitative insights from semi-structured post-study interviews. Participants enrolled in Communication Bridge-2 (NCT03371706, n = 95), a 12-month NIH stage 2 randomized controlled trial of speech-language therapy for PPA, were encouraged to complete app-based home practice exercises five days per week for 30 minutes per day. Usage was measured by weekly logins and completed home practice exercises. Feasibility was assessed through semi-structured post-study interviews (PSI; n = 79). Multi-methods analysis incorporated descriptive statistics and thematic coding of qualitative data. On average, participants logged into the app 5.88 times per week (SD=1.29, range 1.29-18.90) to access exercises and educational materials across the ∼12-month duration of the intervention. On average, users completed 13.7 home practice exercises (SD=5.95) across 3.99 days per week (SD=1.19). PSI dyadic reports indicated few technical challenges with the application (n = 76, 85%) with the most common issues including software updates (n = 12) or connectivity problems (n = 10). Most (n = 80, 90%) found the computer-based format helpful, and many (n = 26, 29%) described the app as user-friendly and intuitive after initial training. Participants highlighted the app's role in fostering confidence and motivation for home communication practice. This study demonstrates high usage and feasibility of web applications to support communication and language intervention in PPA. Importantly, all participants logged into the app and completed home practice exercises at least weekly. Most participants experienced minimal technical challenges and found the web-based format easy to use following a brief technology orientation. These findings challenge assumptions about technology use in older adults with cognitive-communication impairments and provide support for web applications as viable tools for supporting evidence-based speech-language home practice exercises and educational videos to individuals with PPA and their communication partners.

Primary progressive aphasia (PPA) is a currently incurable language-based neurodegenerative dementia syndrome, which negatively impacts communication and quality of life. The Communication Bridge-2 (CB2) trial was the first international telemedicine speech-language (RCT) to show efficacy for persons with PPA. Despite the promising results of the CB2 trial, translating these findings into routine clinical practice poses an urgent and significant challenge. Primary, secondary, and stakeholder data were used to assess readiness for pragmatic randomized controlled trials and implementation. CB2 was an internationally enrolling, single enrollment site, Phase 2, Stage 2, parallel-group, active control, behavioral RCT delivered via video-chat to individuals with PPA and their communication partners. Participation was ∼12 months. A custom web application supported CB2 delivery. Post-study interviews (PSI) conducted with the dyad and a research clinician blinded to intervention arm captured participant experiences and informed Readiness Assessment for Pragmatic Trials (RAPT) ratings. Outcomes were compared between arms qualitatively and using the cumulative logit link in which groups were compared using proportional odds at each evaluation. Ninety-five PPA participant dyads (mean enrollment age of PPA participants: 67.1 years, 48% female) were randomized (n = 4 countries). Dropout was <10%. PSI assessed the dyad-perceived impact of the intervention on everyday life and provided data regarding the feasibility and acceptability of the intervention, aligned with the RAPT model. Reports were positive for both arms; however, responses favored the Experimental arm for positive changes in communication in daily activities (Odds Ratio (OR):2.9, p = 0.073), positive changes in emotional wellbeing (OR:1.4, p = 0.47), overall helpfulness of the speech therapy intervention (OR:4.4, p = 0.083), and reached between group significance in meeting overall expectations of the intervention (OR:5.4, p = 0.005). Participants in both groups showed high usage and feasibility in using the home exercise app. Improving outcomes for PPA, Alzheimer's disease, and Related Dementias (ADRD) requires ensuring that evidence-based interventions are accessible, scalable, and integrated into real-world settings. Evidence from CB2 and stakeholder feedback indicates the intervention is on a strong path towards implementation. These data provide a model for developing future ADRD non-pharmacologic interventions.

Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized by progressive language decline. Access to care for individuals living with PPA is limited by a shortage of evidence-based interventions and qualified clinicians. While technology-supported approaches show promise in improving access to care, there has been no systematic exploration of the factors affecting web application use in this population. This study evaluated the usage and feasibility of an app-based intervention through quantitative application engagement data and qualitative insights from semi-structured post-study interviews. Participants enrolled in Communication Bridge-2 (NCT03371706, N = 95), a 12-month NIH stage 2 randomized controlled trial of speech-language therapy for PPA, were encouraged to complete app-based home practice exercises five days per week for 30 minutes per day. Usage was measured by weekly logins and completed home practice exercises. Feasibility was assessed through semi-structured post-study interviews (PSI; N = 79). Multi-methods analysis incorporated descriptive statistics and thematic coding of qualitative data. On average, participants logged into the app 5.88 times per week (SD=1.29, range 1.29-18.90) to access exercises and educational materials across the ∼12-month duration of the intervention. On average, users completed 13.7 home practice exercises (SD=5.95) across 3.99 days per week (SD=1.19). PSI dyadic reports indicated few technical challenges with the application (n = 76, 85%) with the most common issues including software updates (n = 12) or connectivity problems (n = 10). Most (n = 80, 90%) found the computer-based format helpful, and many (n = 26, 29%) described the app as user-friendly and intuitive after initial training. Participants highlighted the app's role in fostering confidence and motivation for home communication practice. This study demonstrates high usage and feasibility of web applications to support communication and language intervention in PPA. Importantly, all participants logged into the app and completed home practice exercises at least weekly. Most participants experienced minimal technical challenges and found the web-based format easy to use following a brief technology orientation. These findings challenge assumptions about technology use in older adults with cognitive-communication impairments and provide support for web applications as viable tools for supporting evidence-based speech-language home practice exercises and educational videos to individuals with PPA and their communication partners.

Primary Progressive Aphasia (PPA) is a clinical dementia syndrome characterized by progressive language decline. Access to care for individuals living with PPA is limited by a shortage of evidence-based interventions and qualified clinicians. While technology-supported approaches show promise in improving access to care, there has been no systematic exploration of the factors affecting web application use in this population. This study evaluated the usage and feasibility of an app-based intervention through quantitative application engagement data and qualitative insights from semi-structured post-study interviews. Participants enrolled in Communication Bridge-2 (NCT03371706, n = 95), a 12-month NIH stage 2 randomized controlled trial of speech-language therapy for PPA, were encouraged to complete app-based home practice exercises five days per week for 30 minutes per day. Usage was measured by weekly logins and completed home practice exercises. Feasibility was assessed through semi-structured post-study interviews (PSI; n = 79). Multi-methods analysis incorporated descriptive statistics and thematic coding of qualitative data. On average, participants logged into the app 5.88 times per week (SD=1.29, range 1.29-18.90) to access exercises and educational materials across the ∼12-month duration of the intervention. On average, users completed 13.7 home practice exercises (SD=5.95) across 3.99 days per week (SD=1.19). PSI dyadic reports indicated few technical challenges with the application (n = 76, 85%) with the most common issues including software updates (n = 12) or connectivity problems (n = 10). Most (n = 80, 90%) found the computer-based format helpful, and many (n = 26, 29%) described the app as user-friendly and intuitive after initial training. Participants highlighted the app's role in fostering confidence and motivation for home communication practice. This study demonstrates high usage and feasibility of web applications to support communication and language intervention in PPA. Importantly, all participants logged into the app and completed home practice exercises at least weekly. Most participants experienced minimal technical challenges and found the web-based format easy to use following a brief technology orientation. These findings challenge assumptions about technology use in older adults with cognitive-communication impairments and provide support for web applications as viable tools for supporting evidence-based speech-language home practice exercises and educational videos to individuals with PPA and their communication partners.

SuperAgers-individuals aged 80 and older who perform episodic memory tasks at least as well as those 20 to 30 years younger-provide valuable insights into cognitive resilience and resistance to neurodegeneration. The SuperAging Research Initiative (SRI), led by researchers at the University of Chicago, aims to advance research on SuperAgers, particularly emphasizing increasing Black representation in aging studies. In 2022, the SRI established its first Canadian site at Western University in partnership with the University of Waterloo and Sunnybrook Research Institute, capitalizing on the province's historical significance in Black migration to Canada alongside Western's leadership in aging research. This presentation will outline a strategic university-community partnership for recruiting and retaining SRI participants in Canada. In 2023, we commenced recruiting and enrolling a targeted sample of 100 Canadian SuperAgers and controls. Western University is the lead enrollment site. In collaboration with community partners, Western Media/Communications teams, the SRI sites, and SuperAging participants, we developed a multifaceted community-engaged research (CER) strategy and branding campaign tailored to the Canadian consortium. We facilitated 16 media appearances and organized five community events. We trained SRI participant volunteers to serve as ambassadors, engaging with organizations, hosting information sessions, and co-designing marketing materials. Through this campaign, thirteen new strategic partnerships emerged with faith communities, political and community leaders, social clubs, historical societies, medical practices, libraries, and community centers. CER efforts attracted interest from 121 age-eligible individuals, with 55 completing at least one baseline visit, exceeding our 50% enrollment target, with 0% attrition of eligible participants at two-year follow-up. Half of the study enrollments are directly attributed to SRI ambassador activities. Highlighting the persistence required to establish community partnerships, the first Black participant enrolled twenty months after site approvals. These findings underscore the effectiveness of a multifaceted strategy for recruiting healthy octogenarians and nonagenarians. They also emphasize the importance of involving community partners and peer ambassadors in recruitment and retention efforts. Importantly, our experiences highlight the time and significant resources necessary to cultivate and maintain partnerships and community trust for the successful engagement of individuals 80 and older in research, particularly those from diverse communities.