AMYPAD Prognostic and Natural History Study (PNHS), an open label, prospective, multicentre, cohort study in individuals without dementia to evaluate the additional value of quantitative amyloid imaging in determining Alzheimer*s Disease (AD) dementia risk

The Amyloid Imaging to Prevent Alzheimer*s Disease (AMYPAD) Prognostic and
Natural History Study (PNHS) is planned as an open label, prospective,
multicentre, cohort study linked to the European Prevention of Alzheimer*s
Dementia (EPAD) Longitudinal Cohort Study (LCS). For the purpose of phenotyping
and disease modelling, the EPAD LCS employs the concept of an Alzheimer*s
Disease (AD) risk probability spectrum that comprises three main dimensions -
research participant clinical outcomes (e.g. cognition), disease biomarkers,
and traditional risk factors (genetic and environmental). With the
incorporation of longitudinal change scores as relevant, these dimensions are
used to estimate an individual*s overall predicted probability of AD-related
decline in terms of a variety of outcomes.

AMYPAD PNHS is a natural history study that will evaluate how amyloid imaging
might help improve the understanding of the natural course of AD. The study
will assess amyloid positron emission tomography (PET) imaging as an additional
and potentially relevant AD biomarker to complement the phenotyping and disease
modelling efforts of parent cohorts (PC) such as EPAD LCS. As measured from
[18F]flutemetamol and [18F]florbetaben PET images, brain amyloid load will be
quantified at baseline and mean change in amyloid load over at least 12 months
will be estimated. The ability to accurately estimate in vivo amyloid load
could lead to a better understanding of disease evolution, earlier detection of
the disease, and enable researchers to objectively monitor change in amyloid
load to measure the impact of novel therapies.

The aim of this study is to evaluate the additional value of quantitative
amyloid imaging analysis for modelling and assessing Alzheimer*s Disease (AD)
dementia risk in individuals without dementia, compared to a range of existing
cognitive, imaging, laboratory and genetic biomarkers. Risk modelling will be
performed to determine the optimal combination of quantitative amyloid imaging
and other biomarker measures to determine placement of individuals on an AD
risk probability spectrum.

The AMYPAD PNHS study is an observational study where an invasive measurement
is performed (i.e. amyloid PET scan) in a sub-population of the participants of
different parent cohorts (e.g. EPAD LCS/PreclinAD/EMIF-AD 90+/AMYPAD DPMS etc).

Eligible Parent Cohorts (PCs):

The main PC for AMYPAD PNHS is the EPAD LCS. Additional PCs can be added at the
discretion of the Sponsor, as long as they fulfill the following criteria:

1. The PC recruits or has recruited non-demented participants of at least 50
years of age;
2. Participants in the PC have information available on each of the domains of
the AD risk probability spectrum (clinical outcomes (including but not limited
to cognition), disease biomarkers (including but not limited to CSF or MRI
measures), and traditional risk factors (genetic and environmental));

Participants of AMYPAD PNHS will undergo a baseline amyloid PET scan and around
50% of those will get invited for a second follow-up amyloid PET scan at least
12 months after baseline. In case PCs do not acquire essential variables for
primary analyses, AMYPAD PNHS can request for additional data collection (i.e.
RBANS, MMSE, CDR, 3D T1 MRI, medication and changes to medical history)
following appropriate informed consent.

Risks associated with participation in this study are related to:
- radiation exposure
- idiosyncratic reaction to the radiotracer injection
- placement of the intra-venous catheter
- discomfort during the PET scan
- incidental findings