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ObjectiveThe efficacy of spoken language comprehension therapies for persons with aphasia remains equivocal. We investigated the efficacy of a self-led therapy app, ‘Listen-In’, and examined the relation between brain structure and therapy response.MethodsA cross-over randomised repeated measures trial with five testing time points (12-week intervals), conducted at the university or participants' homes, captured baseline (T1), therapy (T2-T4) and maintenance (T5) effects. Participants with chronic poststroke aphasia and spoken language comprehension impairments completed consecutive Listen-In and standard care blocks (both 12 weeks with order randomised). Repeated measures analyses of variance compared change in spoken language comprehension on two co-primary outcomes over therapy versus standard care. Three structural MRI scans (T2-T4) for each participant (subgroup, n=25) were analysed using cross-sectional and longitudinal voxel-based morphometry.ResultsThirty-five participants completed, on average, 85 hours (IQR=70–100) of Listen-In (therapy first, n=18). The first study-specific co-primary outcome (Auditory Comprehension Test (ACT)) showed large and significant improvements for trained spoken words over therapy versus standard care (11%, Cohen’s d=1.12). Gains were largely maintained at 12 and 24 weeks. There were no therapy effects on the second standardised co-primary outcome (Comprehensive Aphasia Test: Spoken Words and Sentences). Change on ACT trained words was associated with volume of pretherapy right hemisphere white matter and post-therapy grey matter tissue density changes in bilateral temporal lobes.ConclusionsIndividuals with chronic aphasia can improve their spoken word comprehension many years after stroke. Results contribute to hemispheric debates implicating the right hemisphere in therapy-driven language recovery. Listen-In will soon be available on GooglePlay.Trial registration numberNCT02540889.

BackgroundA mutation in C9orf72 constitute a cross-link between amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). At clinical manifestation, both patient groups may present with either cognitive impairment of predominantly behaviour or language (in FTD) or motor dysfunctions (in ALS).MethodsIn total, 36 non-symptomatic mutation carriers from ALS or FTD families were examined, including 21 subjects with C9orf72 and 15 with SOD1 mutations. Data were compared with 91 age-matched, education-matched and gender-matched healthy subjects (56 were first-degree relatives from ALS or FTD families, 35 with no known family history of ALS/FTD). MRI scanning for diffusion tensor imaging was performed to map fractional anisotropy (FA). Subjects performed an extensive neuropsychological assessment to address verbal fluency, language, executive, memory and visuospatial function. Measurements were repeated after 12 months.ResultsC9orf72 expansion carriers performed significantly worse in verbal fluency and non-verbal memory and presented with distinct alterations in structural white matter integrity indicated by lower FA values in inferior and orbitofrontal cortical areas compared with carriers of SOD1 mutations or healthy subjects. Loss of structural integrity was associated with decreased verbal fluency performance. White matter alterations and cognitive performance showed no changes over 12 months in all subjects.DiscussionReduced verbal fluency performance seems to be a distinct clinical feature of C9orf72 carriers before symptomatic disease onset without evidence for change over time in our cohort. The results support the emerging hypothesis of a general disorder in development in addition to neurodegeneration in C9orf72 carriers.

ObjectiveRecent evidence has fuelled the debate on the role of massed practice in the rehabilitation of chronic post-stroke aphasia. Here, we further determined the optimal daily dosage and total duration of intensive speech-language therapy.MethodsIndividuals with chronic aphasia more than 1 year post-stroke received Intensive Language-Action Therapy in a randomised, parallel-group, blinded-assessment, controlled trial. Participants were randomly assigned to one of two outpatient groups who engaged in either highly-intensive practice (Group I: 4 hours daily) or moderately-intensive practice (Group II: 2 hours daily). Both groups went through an initial waiting period and two successive training intervals. Each phase lasted 2 weeks. Co-primary endpoints were defined after each training interval.ResultsThirty patients—15 per group—completed the study. A primary outcome measure (Aachen Aphasia Test) revealed no gains in language performance after the waiting period, but indicated significant progress after each training interval (gradual 2-week t-score change [CI]: 1.7 [±0.4]; 0.6 [±0.5]), independent of the intensity level applied (4-week change in Group I: 2.4 [±1.2]; in Group II: 2.2 [±0.8]). A secondary outcome measure (Action Communication Test) confirmed these findings in the waiting period and in the first training interval. In the second training interval, however, only patients with moderately-intensive practice continued to make progress (Time-by-Group interaction: P=0.009, η2=0.13).ConclusionsOur results suggest no added value from more than 2 hours of daily speech-language therapy within 4 weeks. Instead, these results demonstrate that even a small 2-week increase in treatment duration contributes substantially to recovery from chronic post-stroke aphasia.

Background Evidence on preventing Alzheimer’s disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose evidence-based suggestions on AD prevention. Methods Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency and imprecision. Levels of evidence and classes of suggestions were summarised. Results A total of 44 676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). Interpretation Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique inducing prolonged brain excitability changes and promoting cerebral plasticity, is a promising option for neurorehabilitation. Here, we review progress in research on tDCS and language functions and on the potential role of tDCS in the treatment of post-stroke aphasia. Currently available data suggest that tDCS over language-related brain areas can modulate linguistic abilities in healthy individuals and can improve language performance in patients with aphasia. Whether the results obtained in experimental conditions are functionally important for the quality of life of patients and their caregivers remains unclear. Despite the fact that important variables are yet to be determined, tDCS combined with rehabilitation techniques seems a promising therapeutic option for aphasia.

Introduction Existing literature suggests that the presence or absence of apraxia and associated parietal deficits may be clinically relevant in differential diagnosis of dementia syndromes. Aim This study investigated the profile of these features in Alzheimer's disease (AD) and frontotemporal dementia (FTD) spectrum disorders, at first presentation. Methods Retrospective case note analysis was undertaken in 111 patients who presented to the Oxford Cognitive Disorders Clinic, Oxford, UK, including 29 amnestic AD, 12 posterior cortical atrophy (PCA), 12 logopenic primary progressive aphasia (lvPPA), 20 behavioural variant FTD (bvFTD), 7 non-fluent variant PPA (nfvPPA), 6 semantic variant PPA (svPPA) and 25 patients with subjective cognitive impairment (SCI). The clinical features of interest were: limb apraxia, apraxia of speech (AOS), and left parietal symptoms of dyslexia, dysgraphia, and dyscalculia. Results The prevalence of limb apraxia was highest in PCA, amnestic AD, lvPPA and nfvPPA. AOS was only observed in nfvPPA. Associated parietal features were more prevalent in AD spectrum than FTD spectrum disorders. Group comparisons between key differential diagnostic challenges showed that lvPPA and nfvPPA could be significantly differentiated on the presence of left parietal features and AOS, and amnestic AD could be differentiated from bvFTD, svPPA and SCI by limb apraxia. Regression analysis showed that limb apraxia could successfully differentiate between AD and FTLD spectrum disorders with 83% accuracy. Discussion Disease-specific profiles of limb apraxia and associated deficits can be observed. FTD and AD spectrum disorders can be difficult to differentiate due to overlapping cognitive symptoms, and measures of apraxia, in particular, appear to be a promising discriminator.

Background Reward has been shown to affect attention in healthy individuals, but there have been no studies addressing whether reward influences attentional impairments in patients with focal brain damage. Methods Using two novel variants of a widely-used clinical cancellation task, we assessed whether reward modulated impaired attention in 10 individuals with left neglect secondary to right hemisphere stroke. Results Reward exposure significantly reduced neglect, as measured by total targets found, left-sided targets found and centre of cancellation, across the patient group. Lesion analysis showed that lack of response to reward was associated with damage to the ipsilateral striatum. Conclusions This is the first experimental evidence that reward can modulate attentional impairments following brain damage. These results have significant implications for the development of behavioural and pharmacological therapies for patients with attentional disorders.