The Swedish BioFINDER - Preclinical AD Study

This research study aims to examine biomarkers of Alzheimer's disease 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: Plasma Ab42/Ab40; Diagnostic test: Flutemetamol F18 Injection; Diagnostic test: MRI

• Study Type: Observational
• Enrollment (Estimated): 600

Contacts and Locations

• Study Contact: Name: Oskar Hansson, MD, PhD; Phone Number: +46-40-331000; Email: oskar.hansson@med.lu.se
• Study Contact Backup: Name: Erik Stomrud, MD, PhD; Phone Number: +46-40-331000; Email: erik.stomrud@med.lu.se

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Cognitively unimpaired individuals (50-80 y) Step 1. Cognitively normal individuals will be screened using plasma p-tau217 (Eli Lilly-developed MSD method).

Step 2. CSF AD biomarkers 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 AD biomarkers and 150 with normal AD 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. CSF 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 APOE-E4 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. MMSE ≥26 (aged >65); MMSE ≥27 (aged 50-65)
4. Score of 12 or above on the MoCA telephone
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 AD subgroup (n=450): Amyloid pathology according to CSF AD biomarkers and Aβ-PET scans.

6b. Non-Preclinical AD subgroup (n=150): No sign of preclinical AD using CSF AD biomarkers or Aβ-PET scans.

Exclusion Criteria:

1. Fulfils the criteria for minor or major neurocognitive disorder according to 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: Plasma Ab42/Ab40; Plasma levels of Ab42/Ab40 ratio; Diagnostic test: Flutemetamol F18 Injection; PET imaging of amyloid-β plaques; Diagnostic test: MRI; Different MRI sequences relevant for brain imaging
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: Plasma Ab42/Ab40; Plasma levels of Ab42/Ab40 ratio; Diagnostic test: Flutemetamol F18 Injection; PET imaging of amyloid-β plaques; Diagnostic test: MRI; Different MRI sequences relevant for brain imaging

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 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	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 CSF biomarkers	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 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.

Collaborators and Investigators

• Sponsor: Skane University Hospital
• Collaborators: Lund University

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

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): November 8, 2023
• Last Update Submitted That Met QC Criteria: November 2, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Preclinical Alzheimer, early diagnosis, biomarkers, plasma, CSF, PET
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction; Molecular Mechanisms of Pharmacological Action; Radiopharmaceuticals; Flutemetamol
• 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