Protocol for the Tallaght University Hospital Institute for Memory and Cognition-Biobank for Research in Ageing and Neurodegeneration

Introduction Alzheimer’s disease and other dementias affect >50 million individuals globally and are characterised by broad clinical and biological heterogeneity. Cohort and biobank studies have played a critical role in advancing the understanding of disease pathophysiology and in identifying novel diagnostic and treatment approaches. However, further discovery and validation cohorts are required to clarify the real-world utility of new biomarkers, facilitate research into the development of novel therapies and advance our understanding of the clinical heterogeneity and pathobiology of neurodegenerative diseases. Methods and analysis The Tallaght University Hospital Institute for Memory and Cognition Biobank for Research in Ageing and Neurodegeneration (TIMC-BRAiN) will recruit 1000 individuals over 5 years. Participants, who are undergoing diagnostic workup in the TIMC Memory Assessment and Support Service (TIMC-MASS), will opt to donate clinical data and biological samples to a biobank. All participants will complete a detailed clinical, neuropsychological and dementia severity assessment (including Addenbrooke’s Cognitive Assessment, Repeatable Battery for Assessment of Neuropsychological Status, Clinical Dementia Rating Scale). Participants undergoing venepuncture/lumbar puncture as part of the clinical workup will be offered the opportunity to donate additional blood (serum/plasma/whole blood) and cerebrospinal fluid samples for longitudinal storage in the TIMC-BRAiN biobank. Participants are followed at 18-month intervals for repeat clinical and cognitive assessments. Anonymised clinical data and biological samples will be stored securely in a central repository and used to facilitate future studies concerned with advancing the diagnosis and treatment of neurodegenerative diseases. Ethics and dissemination Ethical approval has been granted by the St. James’s Hospital/Tallaght University Hospital Joint Research Ethics Committee (Project ID: 2159), which operates in compliance with the European Communities (Clinical Trials on Medicinal Products for Human Use) Regulations 2004 and ICH Good Clinical Practice Guidelines. Findings using TIMC-BRAiN will be published in a timely and open-access fashion.


PART 1 -THE STUDY
Why is this study being done?
Our research aims to learn more about why people develop memory problems (such as cognitive impairment and dementia).We aim to understand how and why certain people develop these conditions.This includes analysis of clinical information, blood samples as well as lifestyle factors and family history.Additionally, we are trying to develop new tests and methods of diagnosing these conditions.This type of research requires many people to donate samples and data.This study (TIMC-BRAiN) speeds up research by allowing the research team have samples and data ready to use when needed.The aim of this is to improve the diagnosis, management and treatment of memory problems (cognitive impairment and dementia).
Your clinical data and biological samples will be stored until researchers need them in order to answer important questions.Your data and samples may thus be included in many different research studies and for this reason your data and samples may be stored indefinitely (forever).This biobank may share your non-identifiable data with other researchers working around the world.However, no potentially identifiable data will be shared outside of Tallaght University Hospital.

What happens if I take part ?
If you would like to take part, please read this leaflet and sign the consent form at the end.You will be given a copy of this leaflet to keep.A member of the research team will discuss this with you in more detail.If you are happy to take part, the biobank will collect and store • Clinical information from your medical records, including medication history and medication usage in addition to test results from your cognitive assessment (memory tests) • Blood samples: if you are having a routine blood test, the research doctor may take extra samples of blood to give to the biobank This is a small sampleabout 3 tablespoons of blood • Cerebrospinal fluid samples: if you are having a lumbar puncture as part of your memory assessment and diagnosis, the research team may ask to take an extra sample to store in the biobank.This will only take place if you are having a lumbar puncture performed as part of your clinical assessment.There are no lumbar punctures being carried out solely for research purposes.
• Genetic (DNA) Samples: DNA samples will be extracted from blood and samples for research.DNA is the molecule that provides instructions for how cells in our body work.By looking at DNA from people with and without vasculitis we may see differences that are important for diagnosis, treatment or understanding the condition.

What will happen to my clinical data and biological samples ?
All samples and data will be given a random study number in TUH by your study physician in a process called pseudo-anonymisation or "coding".This is intended to mask your identity.All biological samples will be stored in the Meath Foundation laboratory in Tallaght University Hospital using this code.Additionally, your clinical data will be stored on secure databases using this code.Only the study investigators have access to this code and this code will not be shared outside of the study team.
Samples will be stored in a freezer and will remain frozen for decades and potentially indefinitely (forever) so that we can identify future diagnostics and treatment for cognitive impairment and dementia.Samples are being kept indefinitely as scientific research rapidly changes and advances all the time, and we do not yet know what kinds of research questions will arise in the future.The only individuals with direct access to your samples are the investigators of the TIMC-BRAiN study.
Data and samples may be shared with other collaborators.If this is the case, a "Materials Transfer Agreement" will be drawn up by the TIMC-BRAiN study co-ordinators and the collaborating institutions/research groups.This may include samples and data being transferred outside of the European Economic Area (EEA).These samples and data will have all identifying features removed.

What are the benefits to me ?
Research can lead to better diagnostic tests, treatments and quality of life for people with cognitive

What are the risks of participation ? Will I be informed of my results ?
As with any medical records, there is a theoretical risk of accidental disclosure of healthcare data.
However, this is very unlikely as every effort will be made to protect your privacy (see below Section B and Section C).A blood sample may cause bruising or slight discomfort.The additional sample taken at time of diagnostic lumbar puncture poses minimal extra risk (you may be very slightly more likely to experience a post lumbar-puncture headache, however this additional risk is very minimal).
There are additional risks involved in genetic testing.Our genetic testing is entirely focused on the study of the genetics of cognitive impairment and dementia.Therefore it is possible BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Open doi: 10.1136/bmjopen-2023-077772 :e077772.13 2023; BMJ Open , et al.Dyer AH that even if you take part in the study.Even if we do not discover a genetic cause for your condition now, one may still be discovered in the future.It is common that we discover no genetic association for cognitive impairment or dementia or that it takes many years in order to do so.No results will be communicated as a result of genetic testing in this study as this is entirely a research study aimed at discovering genes for cognitive impairment and dementia.Thus, we are not testing for any other genetic mutations of potential clinical significance.

Do I have to take part ?
No, you do not have to take part.Your decision is completely voluntary and will not affect your medical care now or in the future.

What happens if I change my mind ?
You can change your mind at any time.If you contact the study team at any time to inform us that you no longer wish to participate, your samples will be removed from the biobank and destroyed.
Additionally, the clinical data contributed as part of the biobanked will be removed from the biobank database.From that point on, none of your further samples of information will be used as part of the biobank.However, it may not be possible to destroy samples and healthcare data that have already been used for research as this could influence the results of the research.

What happens the results from research ?
Research is usually published in scientific and medical journals or presented at conferences so that other doctors and researchers can learn.You will not be identified in any of these publications or

How is my data stored and shared ?
When you are enrolled in the study, you will be assigned an anonymous study number.The "key" will be stored in TUH on a locked database only accessible to the study investigators.Clinical data and clinical results will be stored on a secure database maintained on servers in Tallaght University Hospital.This will be stored using the REDCap system (Research Electronic Data Capture) which is used globally for the storage of sensitive research data.This will only be accessible by study investigators.
Your clinical data may be shared as: Identifiable Data: the study investigators at the Tallaght Institute of Memory and Cognition may know your identity in order to follow your care and treatment.Only the above named investigators will have access to your identifiable data (ii) Non-identifiable data: researchers working as part of collaborations or research studies outside of the study team (either in Trinity College Dublin, academic partners of TUH, or as part of other researchers) receive "non-identifiable data".This means that information that may identify you has been removed and replaced with a unique code which is used instead of your hospital number, date of birth, address.These researchers work in universities or hospital.Data sharing will only take place as outlined above and your data will not be shared with any external companies or for-profit organisations.

What are my rights ?
TIMC-BRAiN has data protection measures in place and is committed to ensuring that your rights under GDPR (General Data Protection Regulation) are protected.The Department of Age-Related Healthcare is the data controller for this study.We also ask for your consent as a data protection safeguard, in accordance with the Irish Health Research Research Regulations 2018.
• Under the European General Data Protection Regulation (GDPR), the lawful basis for processing your data in this study is for scientific research (Article 9(2) (j)) in the public interest (Article 6(1)(e)).
• Under GDPR, you can exercise the following rights in relation to your personal data, unless the request would make it impossible or very difficult to conduct the research:

CONSENT FORM
To be completed by the participant: I have read and understood the information leaflet for the study.The information has been fully explained to me and I have been able to ask questions, all of which have been answered to my satisfaction YES NO I have had the opportunity to discuss the study, ask questions about the study and I have received satisfactory answers to all my questions.
YES NO I understand that my participation is voluntary, and I can withdraw my biological material and data at any time without giving a reason.I understand that opting out will not affect my future medical care.

YES NO
I understand that sections of my medical notes may be looked at by study investigators at Tallaght Hospital.I give permission for these individuals to access my records.All information will be kept private and confidential.

YES NO
I agree for the entry of my clinical data into the registry.I give explicit informed consent for my data to be processed as part of this research study.I understand that my data will be securely coded and stored indefinitely.

YES NO
I agree to provide blood and (if applicable) cerebrospinal fluid samples for this study as described in the information leaflet.I understand that my samples will be securely coded and stored indefinitely.The risk of taking samples has been explained.

YES NO
I consent for my biological coded samples (including DNA) to be shared with authorised third parties including national and international institutions and academic institutions.I understand that this requires a legal materials transfer agreement between researchers at TUH and these institutions.

YES NO
I agree to be contacted by researchers as part of this study YES NO I consent to undergo venepuncture for the purposes of this study YES NO I consent to participation in this research study having been fully informed of the risks, benefits and purpose of the study YES NO I consent to be contacted with regard to the possible use of my data and/or biological material for future research studies (with consent) YES NO I understand that processing of my personal data, including transfer of data outside the EU, will be protected in accordance with the General Data Protection Regulation YES NO I understand that results from the analysis of my samples will not be given to me.I understand that there are no direct benefits to me and I will not benefit financially in any way.

YES NO
Participant's Name (Block Capitals): Participant's Signature: Date: BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) To be completed by the RESEARCHER: I have fully explained the purpose and nature (including benefits and risks) of this study to the participant in a way that he/she could understand.I have invited him/her to ask questions on any aspect of the study.

YES NO
I confirm that I have given a copy of the information leaflet and consent form to the participant and family member/carer. YES impairment and dementia.The treatments that we have now developed are as a result of past research studies and biobanks.The TIMC biobank collects samples and healthcare data for future research and therefore we cannot predict at this time what research questions will arise in the future and what discoveries these will lead to.It takes many years to do research, so this research may not directly benefit you personally.However, by participating you are contributing to improving the diagnosis, treatment and management of individuals living with cognitive impairment and dementia long into the future.
presentations.The research from TIMC-BRAiN will go on to inform the diagnosis, investigation and treatment of cognitive impairment and dementia into the future.PART 2 -BIOBANK MANAGEMENT How does the TIMC-BRAiN Biobank protect my privacy ?TIMC-BRAiN has very strict governance procedures in place.Only the TIMC-BRAiN team have access to clinical data and biological samples.Only research studies that have been approved by the SJH/TUH JREC Ethics Committee will use clinical data and biological samples.Prof Kennelly and the study team must sign legal agreements before clinical data and biological samples can be shared.This ensures that your samples are only used as agreed.All members of the research team will undergo General Data Protection Regulation (GDPR) training and are bound by hospital confidentiality rules.TIMC-BRAiN ensures that your data is stored in a de-identified "coded" manner on secure servers and only accessible by members of the study team.BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)

oo
The right to access to your data and receive a copy of it o The right to restrict or object to processing of your data o The right to object to any further processing of the information we hold about you (except where it is de-identified) o The right to have inaccurate information about you corrected or deleted BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) The right to receive your data in a portable format and to have it transferred to another data controller o The right to request deletion of your data • You can exercise these rights be contacting your study doctor/study investigator • Under GDPR, if you are not satisfied with how your data is being used, you have the right to lodge a complaint with the Data Protection Commissioner of Ireland or the study Data Protection Officer (dpo@tuh.ie)BMJPublishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance NOBMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)