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

Lanskey, J. H.; Kocagoncu, E.; Quinn, A. J.; Cheng, Y.-J.; Karadag, M.; Pitt, J.; Isaac, J.; Lowe, S.; Perkinton, M.; Raymont, V.; Singh, K. D.; Woolrich, M.; Nobre, A. C.; Henson, R. N.; Rowe, J. B.

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/electro-encephalographic that is sensitive to disease and progression over one 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. Repeat measurements of the clinical, cognitive and imaging data (magnetoencephalography, electroencephalography and magnetic resonance imaging) of participants with Alzheimer's disease or mild cognitive impairment will be taken at baseline and at one year. To assess reliability of magneto/electro-encephalographic changes, a subset of 30 participants with mild cognitive impairment or early-stage Alzheimer's disease will undergo repeat magneto/electro-encephalographic two weeks after baseline. Clinical and cognitive assessment will be repeated at 2 years. Linear mixed models of baseline and longitudinal change in neurophysiology are the primary analyses of interest, supported by Bayesian inference. Additional outputs will include relative effect sizes for physiological markers, atrophy and cognitive change and the respective numbers needed to treat each arm of simulated clinical trials of a future disease modifying therapy. Ethics and dissemination 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.