When we talk about Alzheimer’s disease we mean the changes in the brain that may lead to Alzheimer’s dementia. An individual can have signs of Alzheimer’s disease in the brain without having Alzheimer’s dementia. Alzheimer’s disease may develop into Alzheimer’s dementia, but does not always do so. Alzheimer’s dementia refers to the clinical syndrome where memory and thinking are impaired to the extent that day-to-day functioning of the individual is affected.
We have a duty of care to share the results of any investigation if they are known to be abnormal and clinically relevant, although research participants can choose not to be informed if they wish. However, since it is still not yet known if some of the data we are gathering can be used as a predictor of dementia, by definition, we are not sure what represents an abnormal value and what the implications of some of the tests are. Participants will therefore not, as a matter of course, receive this feedback.
If the study team receives any clinically relevant abnormal values (meaning that the results suggest a potential impact on the participant’s wellbeing) or if new information becomes available that means previous test results are then considered clinically relevant, the study team will contact the participant to discuss these with one of the study doctors.
To make sure that our analyses are not affected by either the participant themselves or the researchers’ personal opinions or perceptions, the results of your genetic tests and measurements of brain scans, blood, urine and spinal fluid biomarkers taken during the study will not be known by either the study team or the participant. Other test results will be known straight away, for example cognitive tests. However, as EPAD is a research study, and not clinical therapy, there is very limited feedback that researchers can give the participants about their test results. This does not mean that there is anything to worry about.
Magnetic Resonance Imaging (MRI) is an established, widely accepted medical way to look in detail at the structure of the brain. MRI is painless, but participants will need to lie still in the scanner for up to 80 minutes and some people can find this claustrophobic. The scanner is also quite noisy, although participants will be wearing ear protection.
The brain scan will be conducted annually while participants are enrolled in the EPAD cohort. At their first visit, if participants have had an MRI scan in the previous year of suitable quality for EPAD, they may not need to undergo another as we may be able to use the previous results.
The examination will include measurement of blood pressure, height, weight, hip and waist circumference. The study doctor will also do a full neurological (senses, power, coordination and reflexes) and cardiac examination. Participants will also be asked to provide information about your medical history, including family history of dementia, and their current medication(s).
The physical examination will be conducted annually while participants are enrolled in the EPAD cohort.
The cognitive assessments will be undertaken using a neuropsychological examination assessing reaction time, function, language skills, memory and attention by means of several tests. The study psychologist or research nurse will provide clear instructions on how to complete the assessments. One of the tests needs the involvement of the study partner too.
The cognitive tests will be conducted at the initial study visit, after six months, and then annually, while participants are enrolled in the EPAD cohort.
Spinal fluid is collected with a procedure called a lumbar puncture. The spinal fluid connects with the spaces within and around the brain so is a very good source of information about what is happening in the brain. This is a commonly conducted test in both research and clinical practice in many parts of Europe.
The procedure takes about an hour in total. Participants will normally be lying on their side, with their legs pulled up and their chin tucked in, but the procedure can also be carried out while they are seated and leaning forwards. Under local anaesthetic, approximately 10 ml of spinal fluid is collected. The lumbar puncture usually takes around 30-45 minutes to complete. After the procedure participants are asked to rest for approximately 30 minutes.
The spinal fluid sample will be taken annually while participants are enrolled in the EPAD cohort. At their first visit, if participants have had a lumbar puncture in the previous year they may not need to have another at this visit as we may be able to use the previous results.
The research is being organised in several European countries under the leadership of the University of Edinburgh, Scotland, UK. EPAD is funded by the European Commission and the European Federation of the Pharmaceutical Industry Association (EFPIA) through the Innovative Medicines Initiative Joint Undertaking (IMI JU). Over time, other sources of funding will be sought to maintain and grow the EPAD cohort of participants and EPAD platform as a whole.