NCT03174938

Brief Summary

The Swedish BioFINDER 2 study is a new study that will launch in 2017 and extends the previous cohorts of BioFINDER 1 study (www.biofinder.se). BioFINDER 1 is used e.g. to characterize the role of beta-amyloid pathology in early diagnosis of Alzheimer's disease (AD) using amyloid-PET (18F-Flutemetamol) and Aβ analysis in cerebrospinal fluid samples. The BioFINDER 1 study has resulted in more than 40 publications during the last three years, many in high impact journals, and some the of the results have already had important implications for the diagnostic work-up patients with AD in the clinical routine practice. The original BioFINDER 1 cohort started to include participants in 2008. Since then there has been a rapid development of biochemical and neuroimaging technologies which enable novel ways to the study biological processes involved in Alzheimer's disease in living people. There has also been a growing interest in the earliest stages of AD and other neurodegenerative diseases. With the advent of new tau-PET tracers there is now an opportunity to elucidate the role of tau pathology in the pathogenesis of AD and other tauopathies. The Swedish BioFINDER 2 study has been designed to complement the BioFINDER 1 study and to e.g. address issues regarding the role of tau pathology in different dementias and in preclinical stages of different dementia diseases. Further, the clinical assessments and MRI methods have been further optimized compared to BioFINDER 1. Detailed assessments of motor aspects and dual task performance, which is part of a sub-study named Motor-ACT: "Motor aspects and activities in relation to cognitive decline and brain pathologies, has been added to further optimize assessment of motor function.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,505

participants targeted

Target at P75+ for not_applicable

Timeline
33mo left

Started May 2017

Longer than P75 for not_applicable

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress77%
May 2017Dec 2028

Study Start

First participant enrolled

May 15, 2017

Completed
13 days until next milestone

First Submitted

Initial submission to the registry

May 28, 2017

Completed
8 days until next milestone

First Posted

Study publicly available on registry

June 5, 2017

Completed
11.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2028

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

April 27, 2025

Status Verified

April 1, 2025

Enrollment Period

11.6 years

First QC Date

May 28, 2017

Last Update Submit

April 23, 2025

Conditions

Keywords

Early diagnosis, biomarker, PET, MRI, β-amyloid, tau, CSF, cognitive test

Outcome Measures

Primary Outcomes (2)

  • Clinical diagnosis

    Clinical diagnosis according to consensus group decision blinded to the diagnostic test

    Clinical diagnosis at last 1 day visit

  • Clinical Dementia Rating-Sum of Boxes (CDR-SB)

    Change in CDR-SB

    Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline.

Secondary Outcomes (4)

  • Rate of cognitive decline as measured by MMSE.

    Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline.

  • Rate of cognitive decline as measured in ADL-function.

    Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline.

  • Rate of volume change of structural MRI measures and amyloid PET

    Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline.

  • Rates of change on cerebrospinal fluid AD biomarkers

    Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 2-8 years after baseline.

Study Arms (5)

COHORT A: Cognitively healthy younger individuals (40-65 y)

OTHER

We will recruit 300 cognitively healthy individuals from the Malmö Offspring study, which is an epidemiological study. The participants will be stratified according to a) family history of dementia in first degree relatives (with onset before 80 years of age) and b) APOE 4 genotype; i.e. 25% will have no family history and no APOE4 allele, 25% will have a family history and no APOE 4 allele, 25% will have no family history and at least one APOE 4 allele, 25% will have a family history and at least one APOE 4 allele. FOLLOW-UP FOR 8 YEARS Every 2 years new clinical, cognitive, neurological, and psychiatric assessments will be performed as well as CSF/blood sampling. MRI, Tau PET and Amyloid PET will be done every 4 years in all cases, and Tau PET and MRI every two years if the subject is amyloid positive at baseline. An auxiliary cohort (termed "Cohort A2") of 40 healthy individuals aged 20-40 years of age will also be included.

Diagnostic Test: Flutemetamol F18 InjectionDiagnostic Test: [18F]-RO6958948Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and PtauDiagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau

COHORT B: Cognitively healthy elderly individuals (66-100 y)

OTHER

We will recruit 300 cognitively healthy individuals from the Malmö/Lund region, where we will aim to include as many individuals as possible that did participate in the Malmö Diet and Cancer study during the early 1990's. The participants will be stratified according to a) family history of dementia in first degree relatives (with onset before 80 years of age) and b) APOE 4 genotype; i.e. 25% will have no family history and no APOE 4 allele, 25% will have a family history and no APOE 4 allele, 25% will have no family history and at least one APOE 4 allele, 25% will have a family history and at least one APOE 4 allele. FOLLOW-UP FOR 8 YEARS Every 2 years new clinical, cognitive, neurological, and psychiatric assessments will be performed as well as CSF/blood sampling. MRI, Tau PET and Amyloid PET will be done every 4 years in all cases, and Tau PET and MRI every two years if the subject is amyloid positive at baseline. Motor assessments (Motor-ACT) are performed at baseline and afte

Diagnostic Test: Flutemetamol F18 InjectionDiagnostic Test: [18F]-RO6958948Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and PtauDiagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau

COHORT C: SCD and MCI

OTHER

\>750 patients with either subjective cognitive decline (SCD) or mild cognitive impairment (MCI) will be recruited in a consecutive fashion from the Skåne University Hospital and Ängelholm Hospital. We will only include cases where the medical doctor believes that the cognitive symptoms are caused by an incipient neurocognitive disorder. For example, cases with evidence of brain amyloid pathology (i.e. an abnormal CSF Aβ42/40 ratio). FOLLOW-UP FOR 6 YEARS Every 12 months new clinical, cognitive, neurological, and psychiatric assessments will be performed. CSF/blood sampling, Tau PET, Amyloid PET and MRI will be done every 2 years. Motor assessment (Motor-ACT) at year 1, year 3 and year 5. A auxiliary cohort ("Cohort C2") \>150 cases with SCD/MCI where the doctor does not suspect incipient neurocognitive disorder, will undergo the same baseline investigations, but they will be followed up clinically only after 2, 4 and 8 y. In total, 1000 patients with SCD or MCI will be included.

Diagnostic Test: Flutemetamol F18 InjectionDiagnostic Test: [18F]-RO6958948Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and PtauDiagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau

COHORT D: Dementia due to Alzheimer's disease

OTHER

400 patients with mild to moderate dementia due to Alzheimer's disease (AD) will be recruited from the Skåne University Hospital and Ängelholm Hospital in southern Sweden. We will include at least 50 cases aged 40-65 years of age, at least 200 cases aged 66-79 years of age and at least 50 cases aged 80-100 years of age. FOLLOW-UP FOR 2 YEARS Every 12 months new clinical, cognitive, neurological, and psychiatric assessments will be performed. CSF/blood sampling, Tau PET and MRI will be done at baseline and after 2 years. Amyloid PET is performed at baseline for a subset of this group.

Diagnostic Test: [18F]-RO6958948Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and PtauDiagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau

COHORT E: Other dementias

OTHER

Patients with primary neurodegenerative disorders other than Alzheimer's disease will be recruited: 1. 160 cases with Frontotemporal dementia (FTD)-related disorders, including behavioral variant of FTD (bvFTD), Progressive nonfluent aphasia (PNFA), semantic dementia (SD), Progressive supranuclear palsy (PSP), Corticobasal degeneration (CBD). 2. 50 cases with subcortical Vascular dementia (VaD). 3. 200 cases with either Parkinson's disease (PD), Parkinson's disease with dementia (PDD), Dementia with Lewy Bodies (DLB), Multiple system atrophy (MSA). FOLLOW-UP FOR 2 YEARS Every 12 months new clinical, cognitive, neurological, and psychiatric assessments will be performed. CSF/blood sampling, Tau PET (depends on further funding) and MRI will be done at baseline and after 2 years. No Amyloid PET in this group. Motor assessments (Motor-ACT) are performed at baseline and a 2-year follow-up since 7th Oct 2019.

Diagnostic Test: [18F]-RO6958948Diagnostic Test: Elecsys (Roche) Abeta42, Ttau and PtauDiagnostic Test: Lumipulse (Fujirebio) Abeta42, Ttau and Ptau

Interventions

PET imaging of Abeta amyloid

Also known as: Vizamyl
COHORT A: Cognitively healthy younger individuals (40-65 y)COHORT B: Cognitively healthy elderly individuals (66-100 y)COHORT C: SCD and MCI
[18F]-RO6958948DIAGNOSTIC_TEST

PET imaging of Tau aggregates

COHORT A: Cognitively healthy younger individuals (40-65 y)COHORT B: Cognitively healthy elderly individuals (66-100 y)COHORT C: SCD and MCICOHORT D: Dementia due to Alzheimer's diseaseCOHORT E: Other dementias

Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid

COHORT A: Cognitively healthy younger individuals (40-65 y)COHORT B: Cognitively healthy elderly individuals (66-100 y)COHORT C: SCD and MCICOHORT D: Dementia due to Alzheimer's diseaseCOHORT E: Other dementias

Measurement of Abeta42, Ttau and Ptau in the cerebrospinal fluid

COHORT A: Cognitively healthy younger individuals (40-65 y)COHORT B: Cognitively healthy elderly individuals (66-100 y)COHORT C: SCD and MCICOHORT D: Dementia due to Alzheimer's diseaseCOHORT E: Other dementias

Eligibility Criteria

Age20 Years - 100 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 40-65 years
  • Absence of cognitive symptoms as assessed by a physician with special interest in cognitive disorders.
  • MMSE score 27-30 at screening visit.
  • Do not fulfill the criteria for MCI or any dementia according to DSM-V.
  • Speaks and understands Swedish to the extent that an interpreter is not necessary for the patient to fully understand the study information and cognitive tests.

You may not qualify if:

  • Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
  • Current significant alcohol or substance misuse.
  • Significant neurological or psychiatric illness.
  • Refusing lumbar puncture, MRI or PET.
  • Age 66-100 years
  • Absence of cognitive symptoms as assessed by a physician with special interest in cognitive disorders.
  • MMSE score 26-30 at screening visit.
  • Do not fulfill the criteria for MCI or any dementia according to DSM-V.
  • Speaks and understands Swedish to the extent that an interpreter is not necessary for the patient to fully understand the study information and cognitive tests.
  • Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study.
  • Current significant alcohol or substance misuse.
  • Significant neurological or psychiatric illness.
  • Refusing lumbar puncture, MRI or PET.
  • Age 40-100 years.
  • Referred to the memory clinics due to cognitive symptoms experienced by the patient and/or informant. These symptoms do not have to be memory complaints, but could also be executive, visuospatial, language, praxis, psychomotor or social cognitive complaints.
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Memory Clinic, Hospital of Ängelholm

Ängelholm, SE-262 81, Sweden

RECRUITING

Memory Clinic, Skåne University Hospital

Malmo, SE-20502, Sweden

RECRUITING

Related Publications (1)

  • Cullen N, Janelidze S, Palmqvist S, Stomrud E, Mattsson-Carlgren N, Hansson O; Alzheimer's Disease Neuroimaging Initiative. Association of CSF Abeta38 Levels With Risk of Alzheimer Disease-Related Decline. Neurology. 2022 Mar 1;98(9):e958-e967. doi: 10.1212/WNL.0000000000013228. Epub 2021 Dec 22.

MeSH Terms

Conditions

DementiaAlzheimer DiseaseParkinson DiseaseLewy Body DiseaseProgressive supranuclear palsy atypicalFrontotemporal DementiaPrimary Progressive Nonfluent AphasiaSupranuclear Palsy, ProgressiveCorticobasal DegenerationMultiple System AtrophyCognitive DysfunctionDiseasePick Disease of the Brain

Condition Hierarchy (Ancestors)

Brain DiseasesCentral Nervous System DiseasesNervous System DiseasesNeurocognitive DisordersMental DisordersTauopathiesNeurodegenerative DiseasesParkinsonian DisordersBasal Ganglia DiseasesMovement DisordersSynucleinopathiesFrontotemporal Lobar DegenerationTDP-43 ProteinopathiesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesAphasia, Primary ProgressiveAphasiaSpeech DisordersLanguage DisordersCommunication DisordersNeurobehavioral ManifestationsNeurologic ManifestationsSigns and SymptomsPathological Conditions, Signs and SymptomsOphthalmoplegiaOcular Motility DisordersCranial Nerve DiseasesParalysisEye DiseasesPrimary DysautonomiasAutonomic Nervous System DiseasesCognition DisordersPathologic Processes

Study Officials

  • Oskar Hansson, MD, Professor

    Skåne University Hospital, and Lund University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Oskar Hansson, MD, Professor

CONTACT

Erik Stomrud, MD, PhD

CONTACT

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
DIAGNOSTIC
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
M.D., PhD

Study Record Dates

First Submitted

May 28, 2017

First Posted

June 5, 2017

Study Start

May 15, 2017

Primary Completion (Estimated)

December 31, 2028

Study Completion (Estimated)

December 31, 2028

Last Updated

April 27, 2025

Record last verified: 2025-04

Locations