The Swedish BioFINDER - Preclinical AD Study

This research study aims to examine biomarkers of Alzheimer's disease (AD) as early as possible which could potentially be a screening tool for the general population. This observational study will take place at the Skåne University Hospital in Sweden. The study will enroll up to 600 cognitively healthy subjects aged 50 to 80 years with 3/4 having preclinical Alzheimer's disease. Recruitment and enrollment will be ongoing for 2-3 years, and subject participation will be lasting approximately 4 years. Disclosure of AD risk assessments will be an optional procedure.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Mild Cognitive Impairment; Mild Dementia
• Intervention / Treatment: Diagnostic test: [18F]-RO6958948 Injection; Diagnostic test: Plasma tau; Diagnostic test: Flutemetamol F18 Injection; Diagnostic test: Magnetic resonance imaging (MRI); Diagnostic test: Plasma β-Amyloid 42/40 (Aβ42/Aβ40)

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: Erik Stomrud, MD, PhD; Phone Number: +46 40 33 10 00; Email: erik.stomrud@med.lu.se
• Study Contact Backup: Name: Niklas Mattsson-Carlgren, MD, PhD; Phone Number: +46 40 33 10 00; Email: niklas.mattsson-carlgren@med.lu.se

Study Locations

• Sweden
  • Malmo, Sweden
    • Recruiting
    • Skåne University Hospital
    • Contact: Erik Stomrud, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Cognitively unimpaired individuals (50-80 years old) Step 1. Cognitively normal individuals will be screened using plasma p-tau217 (Eli Lilly-developed Meso Scale Discovery method).

Step 2. Cerebrospinal fluid Alzheimer's disease biomarkers analysis will be done in a subpopulation including all plasma p-tau217 positive individuals and randomly selected individuals with normal p-tau217 (matching 9:1).

Step 3. Amyloid PET imaging.

450 individuals with positive Alzheimer's disease biomarkers and 150 with normal Alzheimer's disease biomarkers will be enrolled into longitudinal study.

FOLLOW-UP FOR 4 YEARS: Cognitive testing and blood draws will be conducted at baseline and 12, 24, 36 and 48 months. cerebrospinal fluid collection, MRI, amyloid PET and tau PET will be conducted at baseline, and 24 and 48 months.

Description

Inclusion Criteria:

1. Age 50-80

2. Individuals aged 50-60 require at least one of the following risk factors for AD:

   1. Known apolipoprotein E (APOE) -ε4 carrier
   2. Known 1st degree family history of dementia or severe memory loss with onset prior to 75.
   3. Known amyloid brain pathology by either CSF or PET scan.
3. Mini-Mental State Examination (MMSE) ≥26 (aged >65); MMSE ≥27 (aged 50-65).
4. Score of 12 or above on the Montreal Cognitive Assessment (MoCA) telephone version.
5. Speaks and understands Swedish to the extent that an interpreter is not necessary to fully understand the study information and cognitive tests.

6a. Preclinical Alzheimer's disease subgroup (n=450): Amyloid pathology according to cerebrospinal fluid Alzheimer's disease and amyloid PET scans.

6b. Non-Preclinical Alzheimer's disease subgroup (n=150): No sign of preclinical Alzheimer's disease using cerebrospinal fluid Alzheimer's disease biomarkers or Aβ-PET scans.

Exclusion Criteria:

1. Fulfils the criteria for minor or major neurocognitive disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
2. History of significant brain injury or other known neurologic disease or insult, resulting in lasting cognitive sequelae that would confound the assessment and staging of potential neurodegenerative disease.
3. Major depression, bipolar disorder, or recurrent psychotic disorders within the past year.
4. History of alcohol and/or substance abuse or dependence within the past year.
5. Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
6. Refusing or unable to complete baseline cognitive and biomarker assessments (i.e., cognitive testing, blood draw, MRI and PET).

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cognitively unimpaired individuals with preclinical Alzheimer's disease; 75% of the recruited population will be cognitively unimpaired individuals with preclinical Alzheimer's disease.	Diagnostic test: [18F]-RO6958948 Injection; PET imaging of Tau aggregates; Diagnostic test: Plasma tau; Plasma levels of different p-tau and np-tau species; Diagnostic test: Flutemetamol F18 Injection; Positron emission tomography (PET) imaging of amyloid-β plaques; Diagnostic test: Magnetic resonance imaging (MRI); Different MRI sequences relevant for brain imaging; Diagnostic test: Plasma β-Amyloid 42/40 (Aβ42/Aβ40); Plasma levels of Aβ42/Aβ40 ratio
Cognitively unimpaired individuals without preclinical Alzheimer's disease.; 25% of the recruited population will be cognitively unimpaired individuals without preclinical Alzheimer's disease.	Diagnostic test: [18F]-RO6958948 Injection; PET imaging of Tau aggregates; Diagnostic test: Plasma tau; Plasma levels of different p-tau and np-tau species; Diagnostic test: Flutemetamol F18 Injection; Positron emission tomography (PET) imaging of amyloid-β plaques; Diagnostic test: Magnetic resonance imaging (MRI); Different MRI sequences relevant for brain imaging; Diagnostic test: Plasma β-Amyloid 42/40 (Aβ42/Aβ40); Plasma levels of Aβ42/Aβ40 ratio

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive function	Rate of cognitive decline as measured by traditional cognitive and behavioral assessments including The Preclinical Alzheimer Cognitive Composite (PACC)	Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.
Change in cognitive function - digital assessment	Rate of cognitive decline as measured by digital cognitive assessments	Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of change in plasma biomarkers	Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for 4 years after baseline.
Rate of change in amyloid PET	Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every two years for 4 years after baseline.
Rate of change in tau PET	Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every two years for 4 years after baseline.
Rate of change in cerebrospinal fluid biomarkers	Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every two years for 4 years after baseline.

Collaborators and Investigators

• Sponsor: Skane University Hospital
• Collaborators: Lund University
• Investigators: Principal Investigator: Erik Stomrud, MD, PhD, Skane University Hospital and Lund University

Publications and helpful links

Helpful Links

• The official webpage of the Swedish BioFINDER study

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: November 2, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Actual): November 8, 2023

Study Record Updates

• Last Update Posted (Actual): April 6, 2026
• Last Update Submitted That Met QC Criteria: April 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Preclinical Alzheimer, early diagnosis, biomarkers, plasma, CSF, PET
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Dementia; Tauopathies; Neurodegenerative Diseases; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Alzheimer Disease; Disease; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Magnetic Resonance Imaging
• Other Study ID Numbers: SAIS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Time Frame: Within one year after study completion
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No