Alzheimer’s disease is a progressive degenerative disease that results in a loss of brain cells. It is the most common form of dementia, affecting 60-80 % of people with dementia above 65 years of age. The most common symptoms of Alzheimer’s dementia are memory impairment, confusion, disorientation in time and place, difficulties with communication and everyday tasks.
In people with Alzheimer’s disease, the brain undergoes changes, including the accumulation of proteins called ‘ß-amyloid’ and Tau in the brain. The accumulation of ß-amyloid and Tau can start more than a decade before clinical symptoms of dementia occur. Although there is no preventive or curative treatment for Alzheimer’s disease yet, researchers are investigating possible interventions to delay the onset of disease. These interventions would then be used by healthy persons during the long ‘preclinical’ period, that is: before any symptoms of Alzheimer’s disease occur.
During the last few years, new conceptual approaches and criteria to describe Alzheimer’s disease have been developed referring to the spectrum of Alzheimer’s disease in three stages: (1) preclinical Alzheimer’s disease, (2) mild cognitive impairment (MCI) due to Alzheimer’s disease, and (3) dementia due to Alzheimer’s disease.
One pathological hallmark of Alzheimer’s disease is the accumulation of ß-amyloid, called ‘amyloid plaques’, in the brain, caused by the overproduction of ß-amyloid and/or the failure of clearance mechanisms. In a healthy brain, the peptide ß-amyloid is broken down and eliminated. In people who develop Alzheimer’s disease, ß-amyloid accumulates between brain cells, interfering with their normal functioning and their connections to other brain cells. Thus, this peptide represents an important therapeutic target for Alzheimer’s disease: if ß-amyloid can again be broken down.
Watch the EPAD amyloid video to know more about ß-amyloid:
Positron Emission Tomography (PET) is a type of neuroimaging, which allows for the visualisation of the amyloid plaques in the brain. It uses small amounts of radioactive materials called tracers. These tracers are ‘attached’ to particular compounds of interest in the brain and injected into the body. A scanner detects signals from the tracer to see how much of the compound of interest is in the brain.
PET tracers have recently been approved for marketing, which allows for wider use of PET imaging to detect ß-amyloid accumulation in the brain. AMYPAD will use two ß-amyloid PET tracers, which are called florbetaben and flutemetamol. As commercial products, they are called NEURACEQTM and VIZAMYLTM.
The Amyloid imaging to prevent Alzheimer’s disease (AMYPAD) project aims to determine the clinical utility of ß-amyloid PET imaging for the understanding, diagnosis and management of Alzheimer’s disease. Moreover, in combination with the European Prevention of Alzheimer’s disease (EPAD) study, the project aims at unraveling the natural history of the disease in the preclinical or presymptomatic stage to assess the predictive value of ß-amyloid PET and ensure correct enrollment of patients into targeted treatment trials.
The first signs of Alzheimer’s disease (i.e. the accumulation of ß-amyloid) can be found in the brain decades before the first symptoms appear. However, ß-amyloid deposition is considered to be a necessary, but not sufficient, step on the path towards the development of Alzheimer’s dementia. The role of ß-amyloid in diagnosing Alzheimer’s disease in its early stages has not yet been fully clarified. AMYPAD will assess whether depiction of brain ß-amyloid can improve the prediction or early diagnosis of Alzheimer’s disease. A good way to assess brain ß-amyloid is PET imaging.
The AMYPAD diagnostic study will select and follow up a clinical population suspected of possible Alzheimer’s disease, focusing on those with subjective cognitive decline and mild cognitive impairment (MCI), to determine the usefulness of ß-amyloid imaging as a diagnostic marker for Alzheimer’s disease.
Researchers believe that intervention at the earliest possible stage of the disease may be an effective way to prevent or reduce the development of Alzheimer’s dementia from the asymptomatic stage or the stage of subjective cognitive decline or mild cognitive impairment (MCI).
For this purpose, the AMYPAD prognostic study will analyse ß-amyloid PET scans from a large population of healthy research participants and research participants who are at the earliest stages of Alzheimer’s disease, to understand the window of opportunity for secondary prevention through ß-amyloid imaging.
AMYPAD will work closely with the EPAD project (www.ep-ad.org), which is working to increase the understanding of the early stages of Alzheimer’s disease and creating a platform to test treatments designed to prevent dementia. The AMYPAD Prognostic and Natural History Study (PNHS) is planned as a sub-study of the EPAD Longitudinal Cohort Study (LCS). AMYPAD PNHS will evaluate how amyloid imaging might help improve the understanding of the natural course of Alzheimer’s disease. In this study, participants enrolled in the EPAD LCS will undergo PET amyloid imaging. Information about LCS participants’ PET amyloid status will be used in the EPAD LCS for disease modeling.
The AMYPAD PNHS study will help improve the understanding of disease pathophysiology. Also it will gather information about research participants, notably about the presence of biomarkers for Alzheimer’s disease, which can be used to select research participants for clinical trials. Also, it makes the inclusion of research participants in clinical trials more efficient: participants from EPAD who are invited to participate in Proof-of-Concept (PoC) trials will have the advantage of being already well-characterized both by the assessments made in EPAD LCS and in AMYPAD PNHS. This prevents the undue inclusion in Alzheimer’s dementia prevention trials of people who are unlikely to develop Alzheimer’s dementia.
At the moment, it is not possible to register on an individual basis for participation in the AMYPAD studies. In fact, potential AMYPAD participants will be recruited from existing population studies and memory clinic cohorts only.
In the case of the AMYPAD Diagnostic study, a patient with cognitive complaints must have visited a memory clinic with a participating physician. He or she can then be invited to take part in the research. If you are curious whether a memory clinic close to you is participating in AMYPAD, you can find the current list of memory clinics and research hospitals here.
For the AMYPAD Prognostic study, only participants involved in the EPAD Longitudinal Cohort Study (LCS) and other non-EPAD cohorts (e.g. EMIF-AD, ALFA+, and others) can be invited for inclusion. For the EPAD LCS, these come from ongoing cohort studies in Europe (defined as Parent Cohorts). All Parent Cohorts that join the EPAD Program will be listed on a ‘virtual’ EPAD Register. Selected Research Participants will move from the Parent Cohort (on the EPAD Register) to the EPAD Cohort and eventually can be invited to the AMYPAD Prognostic study.