Professor Nick Fox
Institute of Neurology, University College London
Improving prevention trials in Alzheimers disease through imaging
There is increasing interest in secondary prevention therapeutic trials
in Alzheimers disease (AD). These studies will enrol asymptomatic
individuals at high risk of AD by virtue of their family history, genetic
status or evidence of cerebral amyloid deposition and incorporate
imaging and fluid biomarkers. They urgently need more evidence to
support the most effective use of these markers.
We will analyse imaging and other data from the Dominantly Inherited
Alzheimers Network (DIAN) study and use these findings to provide
an evidence-base to inform prevention trials. DIAN participants are
studied longitudinally with serial clinical, neuro-psychometric, and
CSF-based measures as well as comprehensive imaging including
amyloid PET and MR (structural, diffusion and functional) imaging.
DIAN has recruited individuals for over six years from 13 centres and
will make available multiple time point assessments from ~200
We will optimise the pre-processing and analysis methods for the
imaging modalities including intra-subject and inter-modality
registration; we will assess the use of these derived measures for
inclusion and end-point purposes; we will compute means and
variances for rates of change for each of the different outcomes; we
will assess composite end-points; we will model different trial design
scenarios using these and other inclusion/outcome approaches.
We will determine sample sizes required to provide appropriate
statistical power for a range of potential trial scenarios and determine
the impact of different inclusion criteria, trial enrichment, follow-up
duration, and the benefits of using run-in designs. Ultimately we aim
to enhance and guide future prevention trials.