European Prevention of Alzheimer's Dementia - Longitudinal Cohort Study (EPAD-LCS)

Alzheimer*s disease (AD) is the leading cause of dementia globally affecting
~7M people in Europe. As the population ages, the number of people with
dementia will rise and a concomitant rise in the dependency ratio means that
the economic burden of AD will increase dramatically from an already high
baseline (~ ¤262 billion in 2015). Attempts to impact on disease progression
pharmacologically in symptomatic populations remain ongoing, but recent results
have been disappointing. There is now consensus that the genesis of AD
pathology predates dementia onset by over 20 years, presenting an opportunity
for disease course modification before dementia onset and even prior to the
appearance of clinical symptoms. With numerous biologically active agents in
late phase trials which affect a range of pathological processes in AD (e.g.
anti-oligomerisation, secretase inhibitors, kinase inhibitors and anti-amyloid
monoclonal antibodies), the key challenge is to accurately identify individuals
with high probability of subsequent AD dementia development, who are suitable
for trial inclusion and willing to participate in secondary prevention studies.
Current proposals for defining an individual*s probability for developing AD
dementia based on either biomarkers or clinical symptoms have been focused on
the stage of AD close to dementia onset. Disease models and their phenotypic
expression needed for probability estimation in earlier stages in the disease
process are less well defined but the subject of intense study currently. It is
important to firstly develop accurate disease models for AD in early disease
stages when people do not yet have symptoms, or express only subjective
complaints of cognitive decline, or have only mild cognitive symptoms. These
people need to be followed-up longitudinally, and they could be recruited into
trials designed to reduce early disease burden or decrease the probability of
developing AD dementia.
To date, trials of potentially disease modifying drugs in AD have followed a
pattern of intervention with a single agent in lengthy and costly trials for
people with dementia or other clinically defined states thought proximal in
time to the onset of dementia. Only a few recent studies have applied adaptive
design principles that could avoid exposing very large numbers of research
participants to doses of experimental drugs that could have been identified as
ineffective earlier in the course of the study. As each trial works in
isolation of other trials, there have been a vast number of research
participants exposed to a placebo arm that could, given the right
infrastructure, have been shared between studies. These traditionally designed
trials have not led to any new licensed drugs for either the symptomatic
treatment of dementia or its secondary prevention for over 10 years. Moreover,
the basis for decisions to move into these trials was often on limited Phase 2
data, which did not fully address uncertainty regarding optimal dosing,
research participant selection and choice of outcome for the confirmatory
study.
The European Prevention of Alzheimer*s Dementia (EPAD) is a project to develop
an environment for and then test multiple different interventions for the
secondary prevention of AD dementia.

1. To provide a well-phenotyped population (readiness population) for the EPAD
PoC trial to minimize trial screening failures
2. To provide a well-phenotyped probability-spectrum population for developing
and continuously improving disease models for AD in individuals without
dementia. The probability continuum spectrum will be derived from three
different dimensions: cognition, biomarkers, and traditional risk factors
(genetic and environmental)
3. To use disease models for assessing where and why research participants fall
in the overall probability continuum spectrum, and thereafter select research
participants for the EPAD PoC trial
4. To provide high quality run in, pre-randomisation data for the EPAD PoC
trial to measure the impact of various interventions against

EPAD LCS is a prospective, multicenter, pan-European, cohort study that will
have a well phenotyped probability-spectrum population to address the dual need
to develop accurate longitudinal models for AD covering the entire disease
course, and to create a pool of highly characterized individuals for the EPAD
PoC trial. EPAD LCS participants will be recruited from different types of
existing PCs across Europe (e.g. memory clinic-based, population-based) to
ensure fast recruitment of a probability-spectrum population covering the
entire continuum of probability for AD dementia development.

- We ask a time investment: On estimation 8 hours for the screening/annual
visits and 2,5 hours for the visit after 6 months.
- Venipuncture: Can hurt and there is a small chance of hemorrhaging.
- Lumbar puncture : Discomfort during the procedure and less than 10% of the
people get a light headache afterwards for a few days.
- MRI scan: During the MRI the participant can experience discomfort because of
the loud noise and discomfort lying down. Also the participant can get
frightened when they are suffering from claustrophobia.

The participants will not receive any direct compensation for participating in
the EPAD LCS. They do however give a contribution to science with the goal to
diagnose and treat Alzheimer's disease in an earlier stage.
If the participants would appreciate to receive blood results (e.g. cholesterol
or blood sugar values), we can provide these to them.