On 3rd November, we presented the first analysis of the EPAD data at CTAD (Clinical Trials on Alzheimer’s Disease) in Boston, USA. This analysis was primarily illustrative as did not come from the first data wave officially to be released when we have full baseline data from our first 500 research participants (due early in the New Year).
We sought to understand how many people in the LCS are currently Amyloid Positive (CSF Ab levels <1,000pg/ml) and what key factors might drive this. In the accompanying slides it was shown that about 65/232 (28%) of the entire sample of 229 Research Participants were Amyloid Positive, with a further 25/232 (11%) being in what is described as the ‘grey zone’ just above the threshold for amyloid positivity (CSF Ab levels between 1,000pg/ml and 1,200pg/ml). With the advent and delivery of PrePAD Velocity we expect the number of people who are CDR=0.5 to increase substantially in the months ahead.
Importantly increasing age [OR=1.08 (95%CI=1.01-1.15); p=0.01], carrying an ApoEe4 allele [OR=2.6 (95% CI=1.27-5.48); p=0.001] and having a first degree relative with a diagnosis of Alzheimer’s dementia [OR=3.1 (95% CI=1.29-8.01); p=0.01] were all significantly associated with amyloid positivity. Hippocampal volume and baseline CDR score were not; though there was a trend suggesting that with increasing RBANS total score (indicating better cognitive function) there were reduced odds of being amyloid positive [OR=0.97 (95% CI=0.94-0.99) p=0.09].
If we were to increase the likelihood of someone being recruited from a parent cohort as being amyloid positive and then being eligible for the interventions in the EPAD pipeline the current data show the combination of CDR=0.5 and ApoEe4 carriage would predict almost 75% of amyloid positivity. We acknowledge these are very early data derived from analysing a small data set. In the months to come as more research participants enter the LCS and more data becomes available we should be able to refine the selection algorithm for parent cohorts, which in turn will allow us to identify opportunities to help enhance parent cohorts with new tests that will help with selecting the right research participants into the EPAD LCS.
The main outcome from the analysis and presentation was that we have demonstrated the potential that EPAD LCS will bring to our understanding of Alzheimer’s dementia in the preclinical and prodromal phase. As the cohort grows in size and research participants continue to be followed up we will contribute more and more to the knowledge required to design and deliver the EPAD Proof of Concept trial.
Early next year, with the formal release of the first wave of data, we anticipate several analyses to be presented at AAIC in Chicago and published in peer-reviewed journals. EPAD has now entered the important phase of data analysis and the delivery of new knowledge. This presentation and subsequent academic outputs are only possible and will only be possible due to the dedication over the last 3 years of literally hundreds of researchers, academics, operational staff and industry experts as well as of course the research participants we partner with to generate the data in a structure which allows rapid analyses, presentation and impact.
Well done to the Epadistas!!!
Craig Ritchie, EPAD Project Co-coordinator