New Therapeutics in Alzheimer's Disease Longitudinal Cohort study (NTAD): study protocol.

INTRODUCTION: With the pressing need to develop treatments that slow or stop the progression of Alzheimer's disease, new tools are needed to reduce clinical trial duration and validate new targets for human therapeutics. Such tools could be derived from neurophysiological measurements of disease. METHODS AND ANALYSIS: The New Therapeutics in Alzheimer's Disease study (NTAD) aims to identify a biomarker set from magneto/electroencephalography that is sensitive to disease and progression over 1 year. The study will recruit 100 people with amyloid-positive mild cognitive impairment or early-stage Alzheimer's disease and 30 healthy controls aged between 50 and 85 years. Measurements of the clinical, cognitive and imaging data (magnetoencephalography, electroencephalography and MRI) of all participants will be taken at baseline. These measurements will be repeated after approximately 1 year on participants with Alzheimer's disease or mild cognitive impairment, and clinical and cognitive assessment of these participants will be repeated again after approximately 2 years. To assess reliability of magneto/electroencephalographic changes, a subset of 30 participants with mild cognitive impairment or early-stage Alzheimer's disease will also undergo repeat magneto/electroencephalography 2 weeks after baseline. Baseline and longitudinal changes in neurophysiology are the primary analyses of interest. Additional outputs will include atrophy and cognitive change and estimated numbers needed to treat each arm of simulated clinical trials of a future disease-modifying therapy. ETHICS AND DATA STATEMENT: The study has received a favourable opinion from the East of England Cambridge Central Research Ethics Committee (REC reference 18/EE/0042). Results will be disseminated through internal reports, peer-reviewed scientific journals, conference presentations, website publication, submission to regulatory authorities and other publications. Data will be made available via the Dementias Platform UK Data Portal on completion of initial analyses by the NTAD study group.

Differential brain-to-brain entrainment while speaking and listening in native and foreign languages.

The study explores interbrain neural coupling when interlocutors engage in a conversation whether it be in their native or nonnative language. To this end, electroencephalographic hyperscanning was used to study brain-to-brain phase synchronization during a two-person turn-taking verbal exchange with no visual contact, in either a native or a foreign language context. Results show that the coupling strength between brain signals is increased in both, the native language context and the foreign language context, specifically, in the alpha frequency band. A difference in brain-to speech entrainment to native and foreign languages is also shown. These results indicate that between brain similarities in the timing of neural activations and their spatial distributions change depending on the language code used. We argue that factors like linguistic alignment, joint attention and brain-entrainment to speech operate with a language-idiosyncratic neural configuration, modulating the alignment of neural activity between speakers and listeners. Other possible factors leading to the differential interbrain synchronization patterns as well as the potential features of brain-to-brain entrainment as a mechanism are briefly discussed. We concluded that linguistic context should be considered when addressing interpersonal communication. The findings here open doors to quantifying linguistic interactions.