Search

Successful communication in daily life depends on accurate decoding of speech signals that are acoustically degraded by challenging listening conditions. This process presents the brain with a demanding computational task that is vulnerable to neurodegenerative pathologies. However, despite recent intense interest in the link between hearing impairment and dementia, comprehension of acoustically degraded speech in these diseases has been little studied. Here we addressed this issue in a cohort of 19 patients with typical Alzheimer's disease and 30 patients representing the three canonical syndromes of primary progressive aphasia (non-fluent/agrammatic variant primary progressive aphasia; semantic variant primary progressive aphasia; logopenic variant primary progressive aphasia), compared to 25 healthy age-matched controls. As a paradigm for the acoustically degraded speech signals of daily life, we used noise-vocoding: synthetic division of the speech signal into frequency channels constituted from amplitude-modulated white noise, such that fewer channels convey less spectrotemporal detail thereby reducing intelligibility. We investigated the impact of noise-vocoding on recognition of spoken three-digit numbers and used psychometric modelling to ascertain the threshold number of noise-vocoding channels required for 50% intelligibility by each participant. Associations of noise-vocoded speech intelligibility threshold with general demographic, clinical and neuropsychological characteristics and regional grey matter volume (defined by voxel-based morphometry of patients' brain images) were also assessed. Mean noise-vocoded speech intelligibility threshold was significantly higher in all patient groups than healthy controls, and significantly higher in Alzheimer's disease and logopenic variant primary progressive aphasia than semantic variant primary progressive aphasia (all P < 0.05). In a receiver operating characteristic analysis, vocoded intelligibility threshold discriminated Alzheimer's disease, non-fluent variant and logopenic variant primary progressive aphasia patients very well from healthy controls. Further, this central hearing measure correlated with overall disease severity but not with peripheral hearing or clear speech perception. Neuroanatomically, after correcting for multiple voxel-wise comparisons in predefined regions of interest, impaired noise-vocoded speech comprehension across syndromes was significantly associated (P < 0.05) with atrophy of left planum temporale, angular gyrus and anterior cingulate gyrus: a cortical network that has previously been widely implicated in processing degraded speech signals. Our findings suggest that the comprehension of acoustically altered speech captures an auditory brain process relevant to daily hearing and communication in major dementia syndromes, with novel diagnostic and therapeutic implications. [ABSTRACT FROM AUTHOR]

Introduction: Behavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present. Methods: We assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI‐R) in 733 participants from the Genetic FTD Initiative study: 466 mutation carriers (195 C9orf72, 76 MAPT, 195 GRN) and 267 non‐mutation carriers (controls). All mutation carriers were stratified according to their global CDR plus NACC FTLD score into three groups: asymptomatic (CDR = 0), prodromal (CDR = 0.5) and symptomatic (CDR = 1+). Mixed‐effects models adjusted for age, education, sex and family clustering were used to compare between the groups. Neuroanatomical correlates of the individual domains were assessed within each genetic group. Results: CBI‐R total scores were significantly higher in all CDR 1+ mutation carrier groups compared with controls [C9orf72 mean 70.5 (standard deviation 27.8), GRN 56.2 (33.5), MAPT 62.1 (36.9)] as well as their respective CDR 0.5 groups [C9orf72 13.5 (14.4), GRN 13.3 (13.5), MAPT 9.4 (10.4)] and CDR 0 groups [C9orf72 6.0 (7.9), GRN 3.6 (6.0), MAPT 8.5 (13.3)]. The C9orf72 and GRN 0.5 groups scored significantly higher than the controls. The greatest impairment was seen in the Motivation domain for the C9orf72 and GRN symptomatic groups, whilst in the symptomatic MAPTgroup, the highest‐scoring domains were Stereotypic and Motor Behaviours and Memory and Orientation. Neural correlates of each CBI‐R domain largely overlapped across the different mutation carrier groups. Conclusions: The CBI‐R detects early behavioural change in genetic FTD, suggesting that it could be a useful measure within future clinical trials. [ABSTRACT FROM AUTHOR]

Background: Behavioural dysfunction is a key feature of genetic frontotemporal dementia (FTD) but validated clinical scales measuring behaviour are lacking at present. Method: We assessed behaviour using the revised version of the Cambridge Behavioural Inventory (CBI‐R) in 733 participants from the Genetic FTD Initiative study: 466 mutation carriers (195 C9orf72, 76 MAPT, 195 GRN) and 267 non‐mutation carriers (healthy controls). All mutation carriers were stratified according to their CDR® plus NACC FTLD into three groups: asymptomatic (CDR=0), mildly symptomatic (CDR=0.5) and fully symptomatic (CDR=1+). CBI‐R total scores were compared between mutation carrier groups using a mixed effects model that adjusted for age, education, sex and family clustering, with 95% bootstrapped confidence intervals with 2000 repetitions to adjust for non‐normally distributed data. We used the same mixed effects model to run a within‐group analysis between the 10 CBI‐R domains in CDR 1+ groups. Spearman rank correlations were run to assess the relationship of the CDR® plus NACC FTLD SOB and FRS scale with the CBI‐R total in CDR 1+ mutation carrier groups. Result: CBI‐R total scores were significantly higher in all CDR 1+ mutation carrier groups compared to controls (C9orf72 mean 70.5 (standard deviation 27.8), GRN 56.2 (33.5), MAPT 62.1 (36.9)), as well as their respective CDR 0.5 groups (C9orf72 13.5 (14.4), GRN 13.3 (13.5), MAPT 9.4 (10.4)) and CDR 0 groups (C9orf72 6.0 (7.9), GRN 3.6 (6.0), MAPT 8.5 (13.3)). Both C9orf72 and GRN 0.5 groups scored significantly higher than controls and their respective CDR 0 groups. Motivation and Memory were the highest scoring domains in both C9orf72 and GRN CDR 1+ groups, and in the MAPT group it was Stereotypic Behaviour and Memory. There was a positive correlation between the CBI‐R scores and the CDR® plus NACC FTLD SOB scores in all mutation carrier groups (C9orf72: rho= 0.8, p<0.001, GRN: rho= 0.8, p<0.001, MAPT: rho= 0.6, p<0.001), and a negative correlation between CBI‐R scores and FTD Rating Scale (FRS) scores (C9orf72; rho= ‐0.9, p<0.001, GRN; rho= ‐0.9, p<0.001, MAPT; rho= ‐0.9, p<0.001). Conclusion: The CBI‐R detects early behavioural change in genetic FTD, particularly in those with C9orf72 and GRN mutations. [ABSTRACT FROM AUTHOR]

Logopenic variant primary progressive aphasia (lvPPA) is the least well defined of the major primary progressive aphasia (PPA) syndromes. We assessed phoneme discrimination in patients with PPA (semantic, nonfluent/agrammatic, and logopenic variants) and typical Alzheimer's disease, relative to healthy age‐matched participants. The lvPPA group performed significantly worse than all other groups apart from tAD, after adjusting for auditory verbal working memory. In the combined PPA cohort, voxel‐based morphometry correlated phonemic discrimination score with grey matter in left angular gyrus. Our findings suggest that impaired phonemic discrimination may help differentiate lvPPA from other PPA subtypes, with important diagnostic and management implications. [ABSTRACT FROM AUTHOR]

Background: Accurately interpreting a speaker's nonverbal emotional vocal signals (their prosody) is often essential for successful communication. In the noisy conditions of daily life, this presents the brain with a difficult computational challenge that may be vulnerable to neurodegenerative pathologies. However, processing of acoustically degraded prosody has not been studied in these diseases. Method: Here we addressed this issue in patients representing all major syndromes of primary progressive aphasia (N = 33) and Alzheimer's disease (N = 18) versus healthy age‐matched controls (N = 24). As a model paradigm for the degraded 'noisy' speech signals of everyday life, we used noise‐vocoding: digital division of the speech signal into a variable number of frequency channels constituted from amplitude‐modulated white noise, such that fewer channels convey less spectrotemporal detail and reduce intelligibility. We assessed the impact of noise‐vocoding on recognition of three canonical prosodic emotions (anger, surprise, sadness) at three noise‐vocoding levels. Correlations were also conducted with perception of degraded emotional prosody and measures of social cognition. Result: Compared with health controls, all patient groups were impaired in the identification of 'clear' emotional prosody. This impairment in all groups was sustained when the emotional prosody stimuli were vocoded, with differences seen between 18 and six channels, and 12 and six channels. Cost analyses conducted showed a significantly larger cost of noise‐vocoding in lvPPA than in healthy controls. Accurate identification of degraded emotional prosody in patients was significantly correlated with measures of social cognition. Conclusion: Our findings open a window on a dimension of real‐world emotional communication that has often been relatively overlooked in dementia, and suggest a novel candidate paradigm for investigating and quantifying this systematically. [ABSTRACT FROM AUTHOR]

BackgroundDespite ongoing prevention efforts, HIV and other sexually transmitted infections (HIV/STIs) and drug use remain public health concerns. Urban adolescents, many of whom are underserved and racial minorities, are disproportionately affected. Recent changes in policy, including the Affordable Care Act, and advances in technology provide HIV/STI and drug abuse prevention scientists with unique opportunities to deliver mobile health (mHealth) preventive interventions in primary care. ObjectivesThe purpose of this community-engaged study was to develop an mHealth version of the Storytelling for Empowerment preventive intervention for primary care (hereinafter referred to as “S4E”). MethodsA total of 29 adolescents were recruited from a youth-centered primary care clinic in Southeast, Michigan, to participate in qualitative interviews. Participants were predominantly African American (n=19, 65.5%) and female (n=21, 72.4%) with a mean age of 16.23 (SD 2.09). The principles of community-based participatory research (CBPR), in conjunction with agile software development and the recommended core prevention principles of the National Institute on Drug Abuse (NIDA) were employed during S4E development. CBPR principles are aimed at improving the effectiveness of research by addressing locally relevant health problems, working with community strengths, and translating basic science into applied research. Complementing this approach, the NIDA prevention principles are derived from decades of drug abuse prevention research aimed at increasing the effectiveness and uptake of programs, through the development of culturally specific interventions and ensuring the structure, content, and delivery of the intervention fit the needs of the community. Data were analyzed using thematic analysis. ResultsA total of 5 themes emerged from the data: (1) acceptability of the mHealth app to adolescents in primary care, (2) inclusion of a risk assessment to improve clinician-adolescent HIV/STI and drug use communication, (3) incorporation of culturally specific HIV/STI and drug use content, (4) incorporation of interactive aspects in the app to engage youth, and (5) perspectives on the appearance of the app. ConclusionsThere is a dearth of mHealth HIV/STI and drug abuse preventive interventions for primary care. Incorporating the principles of CBPR in conjunction with agile software development and NIDA-recommended core prevention principles may be helpful in developing culturally specific mHealth interventions. An important next step in this program of research is to examine the feasibility, acceptability, and efficacy of S4E on adolescent sexual risk and drug use behaviors, and HIV/STI testing. Implications for prevention research and primary care practice are discussed in the context of the Affordable Care Act and technological advances.