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

NCT02804789 | Terminated DMC

• 1 other identifier: EPAD-UoE-001
• Study Type: observational
• Target: 2,095
• Locations: 9 countries
• Sites: 30

Brief Summary

Brain changes associated with Alzheimer's disease may precede symptoms of Alzheimer's Dementia by over 20 years. The Investigators hope to be able to identify Alzheimer's disease at its very earliest stages when in theory treatments are most likely to be successful in preventing further spread of the disease in the brain and causing dementia. The aim of EPAD programme is to develop new treatments more quickly to prevent Alzheimer's dementia. A major component of the EPAD programme is the EPAD Longitudinal Cohort Study which can provide subjects for the EPAD trial as well as data to improve understanding of disease before dementia develops. The Investigators will approach a broad range of people over the age of 50 who have previously taken part in various research studies and consented to being recontacted for further research. Participants will be asked questions to assess their memory and other cognitive function. The participants will also undertake a brain scan, provide a sample of spinal fluid, blood, urine and saliva to look at markers in these bodily fluids that may change in Alzheimer's disease. The Investigators will then follow these participants until December 2019 repeating these tests annually. This will be called the EPAD Longitudinal Cohort Study (EPAD LCS). The main reasons for EPAD developing a cohort are to help the Investigators understand more about what happens to people before dementia develops, and to help recruit people more quickly into the EPAD trials of new medications or other interventions expected to prevent dementia. People in the EPAD LCS may be invited to take part in the EPAD Proof of Concept prevention studies to see if interventions can modify the probability of developing dementia or cognitive problems (this will be subject to separate ethics approval and consent). Together EPAD LCS and EPAD PoC make up the full EPAD Programme.

Conditions

Alzheimer's Dementia

Keywords

Prevention

Outcome Measures

Primary Outcomes (1)

• Change in RBANS Composite score over time, units on a scale.

  Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) Composite score combining: List Learning \& Story Memory; Figure Recall; Figure Copy \& Line Orientation; Picture Naming; Semantic Fluency, Digit Span, Coding.

  Measured at Baseline, 6 months, year 1, year 2, year 3.

Secondary Outcomes (5)

• Change in other Secondary Cognitive Tests score: Working Memory, over time, units on a scale.

  Measured at Baseline, 6 months, year 1, year 2, year 3

• Change in other Secondary Cognitive Tests score: Choice Reaction Time and Set Shifting, over time, units on a scale.

  Measured at Baseline, 6 months, year 1, year 2, year 3

• Change in other Secondary Cognitive Tests score: Paired Associate Learning, over time, units on a scale.

  Measured at Baseline, 6 months, year 1, year 2, year 3

• Change in cerebrospinal fluid (CSF) AD biomarkers over time

  Measured at Baseline, year 1, year 2, year 3

• Changes in neuro-imaging assessment of hippocampal and whole brain volume, over time

  Measured at Baseline, year 1, year 2, year 3

Other Outcomes (26)

• Change in exploratory Cognitive Tests score: Allocentric space, over time, units on a scale.

  Measured at Baseline, 6 months, year 1, year 2, year 3

• Change in exploratory Cognitive Tests score: Egocentric space, over time, units on a scale.

  Measured at Baseline, 6 months, year 1, year 2, year 3

• Change in other secondary clinical outcome scale: Everyday functioning, total over time, units on a scale

  Measured at Baseline, 6 months, year 1, year 2, year 3

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Research participants will mainly be recruited from existing Parent Cohorts (PC) across Europe. PCs considered for EPAD are: active cohorts without dementia aged at least 50 years; the PC PI is willing to provide research participants for EPAD trials; with existing consent for re-contact or possibility to obtain consent to re-contact. Potential research participants will be identified based on data in the PC, using a flexible search algorithm adapted to the types of data available in each PC. Recruitment will be complemented with research participants who are recruited from a clinical setting by their referring clinician. In case an individual or their referring clinician contacts a TDC, the referring clinician will check the flexible algorithm to confirm their suitability.

You may qualify if:

• At least 50 Years of Age
• Characterisation of cognitive, biomarker and risk factors (genetic, environmental) status of research participants based on data collected at the EPAD screening/baseline visit, so that decisions on selection/deselection can be made with reference to the dual needs of having sufficient heterogeneity across the entire probability-spectrum population for disease-modelling work, and suitable research participants for the EPAD PoC trial (Balancing Committee decision)
• Able to read and write with a minimum of 7 years of formal education.
• Willing in principle to participate in the EPAD Proof of Concept Trials (with additional consent).
• Have a study partner or can identify someone willing to be a study partner. The primary role of the study partner will be as informant. They will also receive oral and written information about the EPAD LCS, and will sign an Informed Consent Form (ICF).

You may not qualify if:

• Individuals who fulfill diagnostic criteria for any type of dementia.
• Clinical Dementia Rating \>=1
• Known carriers of a Presenilin (PSEN) 1, PSEN 2 or Amyloid Precursor Protein (APP) mutation associated with Autosomal Dominant Alzheimer's dementia or any other neurodegenerative disease.
• Presence of any neurological, psychiatric or medical conditions associated with a long-term risk of significant cognitive impairment or dementia including but not limited to pre- manifest Huntington's disease, multiple sclerosis, Parkinson's disease, Down syndrome, active alcohol/drug abuse; or major psychiatric disorders including current major depressive disorder, schizophrenia, schizoaffective or bipolar disorder.
• Cancer or history of cancer in the last 5 years (excluding cutaneous basal or squamous cell cancer resolved by excision).
• Any current medical conditions that are clinically significant and might make participation in an investigational trial unsafe, e.g., uncontrolled or unstable disease of any major organ system; history within the last 6 months of any acute illness of a major organ system requiring emergency care or hospitalization, including revascularization procedures; severe renal or hepatic failure; unstable or poorly controlled DM, hypertension, or heart failure; malignant neoplasms within the last 3 years (expect for basal or squamous cell carcinoma in situ of the skin, or localized prostate cancer in male participants); any clinically relevant abnormalities in blood parameters included in local TDC routine assessments; severe loss of vision, hearing or communicative ability; or any conditions preventing co-operation or completion of the required assessments in the trial, as judged by the investigator.
• Contraindications for MRI/Positron emission tomography (PET) Scan.
• Contraindications for Lumbar Puncture.
• Any evidence of intracranial pathology which, in the opinion of the Investigator, may affect cognition including but not limited to brain tumours (benign or malignant), aneurysm or arteriovenous malformations, territorial stroke (excluding smaller watershed strokes), recent haemorrhage (parenchymal or subdural), or obstructive hydrocephalus. Research participants with a MRI scan demonstrating markers of small vessel disease (e.g. white matter changes or lacunar infarcts) judged to be clinically insignificant, or microbleeds are allowed.
• Diminished decision-making capacity/ not capable of consenting at Visit 1 or Visit 2. If at a subsequent annual EPAD LCS visit health professionals suspect diminished consent capacity according to local TDC routine procedures, a formal assessment of the research participant's capacity to consent will be conducted. The participant will be offered the opportunity to continue in the EPAD LCS under suitable local regulations regarding capacitous participants who have consented to enter a longitudinal study who subsequently loose capacity. Capacity will be assessed at each study visit using the correct legal framework.

Sponsors & Collaborators

• University of Edinburgh: lead
• Innovative Medicines Initiative: collaborator

Study Sites (30)

Cliniques Universitaires Saint-Luc ASBL, Neurology Department

Brussels, 1200, Belgium

Location

UZ Leuven, Campus Gasthuisberg

Leuven, 3000, Belgium

Location

CMRR du CHRU de Lille Hôpital Roger Salengro

Lille, 59037 CEDEX, France

Location

CHU Gui de Chauliac Département de Neurologie

Montpellier, 34295 CEDEX 5, France

Location

Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal

Paris, 75475 CEDEX 10, France

Location

Hôpital Universitaire de la Pitié Salpêtrière

Paris, 75651 CEDEX 13, France

Location

CMRR- Hôpital Laënnec Nord - CIC Neurologie / CHU de Nantes

Saint-Herblain, 44800, France

Location

Toulouse University Hospital / Gérontopôle-Research Clinical Center

Toulouse, 31059 Cedex 9, France

Location

National and Kapodistran, University of Athens, 1st Department of Neurology, Aeginition Hospital

Athens, 11528, Greece

Location

Univerita di Perugia, Centro Disturbi della Memoria, Clinica Neurologica

Perugia, Loc. S Andrea Delle Fratte, 06132, Italy

Location

IRCCS San Giovanni di Dio - Fatebenefratelli

Brescia, 25125, Italy

Location

VUmc Alzheimer Center and Alzheimer Research Center

Amsterdam, North Holland, 1081GM, Netherlands

Location

Unidade Deterioro Cognitivo, Servicio de Neurologia, Hospital Universitario

Santander, Cantabria, 39008, Spain

Location

BarcelonaBeta Brain Research Centre

Barcelona, 08005, Spain

Location

Fundacion ACE, Institut Catala de Neurocienies Aplicades

Barcelona, 08028, Spain

Location

Fundacion CITA-alzheimer Fundazioa, Center for Research and Advanced Therapies

San Sebastián, 20009, Spain

Location

Neuropsychiatric Research Unit, Sahlgrenska University Hoospital

Gothenburg, Västra Götaland County, SE-431 41, Sweden

Location

Karolinska Institutet

Stockholm, SE-141 86, Sweden

Location

Hôpitaux Universitaires de Genève - HUG

Geneva, CH-1227, Switzerland

Location

Centre Leenaards de la memoire- CHUV, Department of Neurosciences cliniques

Lausanne, 1011, Switzerland

Location

Monklands University Hospital

Cumbernauld, Lanarkshire, G67 3BE, United Kingdom

Location

University of Edinburgh, Centre for Dementia Prevention

Edinburgh, Midlothian, EH16 4UX, United Kingdom

Location

NHS Grampian

Aberdeen, AB25 2ZH, United Kingdom

Location

North Bristol NHS Trust

Bristol, BS10 5NB, United Kingdom

Location

University of Cambridge; Department of Clinical Neurosciences

Cambridge, CB2 0SZ, United Kingdom

Location

NHS Tayside

Dundee, DD1 9SY, United Kingdom

Location

Glasgow Clinical Research Facility; NHS Greater Glasgow and Clyde

Glasgow, G51 4TF, United Kingdom

Location

West London Mental Health NHS Trust

London, TW7 6FY, United Kingdom

Location

Greater Manchester Clinical Research Network

Manchester, M13 9WL, United Kingdom

Location

University of Oxford, Department of Psychiatry

Oxford, OX3 7JX, United Kingdom

Location

Related Publications (3)

• Osset-Malla M, Martinez-Velasco A, Sanchez-Benavides G, Buongiorno M, de la Sierra A, Shekari M, Minguillon C, Kollmorgen G, Quijano-Rubio C, Zetterberg H, Blennow K, Garcia DV, Suarez-Calvet M, Gispert JD, Grau-Rivera O; ALFA Study. Blood pressure and Alzheimer's disease biomarkers in cognitively unimpaired adults: a multicenter study. J Prev Alzheimers Dis. 2025 Dec;12(10):100304. doi: 10.1016/j.tjpad.2025.100304. Epub 2025 Aug 11.

  PMID: 40796457 DERIVED

• Vermunt L, Muniz-Terrera G, Ter Meulen L, Veal C, Blennow K, Campbell A, Carrie I, Delrieu J, Fauria K, Huesa Rodriguez G, Ingala S, Jenkins N, Molinuevo JL, Ousset PJ, Porteous D, Prins ND, Solomon A, Tom BD, Zetterberg H, Zwan M, Ritchie CW, Scheltens P, Luscan G, Brookes AJ, Visser PJ; IMI-EPAD collaborators. Prescreening for European Prevention of Alzheimer Dementia (EPAD) trial-ready cohort: impact of AD risk factors and recruitment settings. Alzheimers Res Ther. 2020 Jan 6;12(1):8. doi: 10.1186/s13195-019-0576-y.

  PMID: 31907067 DERIVED

• Solomon A, Kivipelto M, Molinuevo JL, Tom B, Ritchie CW; EPAD Consortium. European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS): study protocol. BMJ Open. 2019 Feb 19;8(12):e021017. doi: 10.1136/bmjopen-2017-021017.

  PMID: 30782589 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* Urine * Saliva * CSF * Blood (Serum, Plasma, Whole Blood, RNA, DNA)

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Study Officials

• Craig Ritchie

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 44 Months
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 9, 2016
• First Posted: June 17, 2016
• Study Start: May 1, 2016
• Primary Completion: March 13, 2020
• Study Completion: March 13, 2020
• Last Updated: March 31, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: Post December 2019
• Access Criteria: To be determined by the EPAD Research Access Committee

Locations

BE (2); FR (6); ES (4); NL (1); GB (10); SE (2); IT (2); CH (2); GR (1)