The Swedish BioFINDER Study

NCT01208675 | Completed

• 1 other identifier: TiDiS-2010
• Study Type: observational
• Target: 1,150
• Locations: 1 country
• Sites: 2

Brief Summary

The present study aims at combining biochemical methods with various types of imaging techniques to identify the pathophysiology of Alzheimer's disease (AD). The main interest is to find markers associated with the very early steps in the pathology of this disease. The investigators shall thus screen for i) molecules in cerebrospinal fluid (CSF) and plasma specific for AD, and ii) brain imaging markers (e.g. MRI and PET) that correlate to detailed clinical assessments. Biomarkers of interest would then be useful to:

1. 1.Enable accurate detection of the disease early on. Such biomarkers need to specifically reflect the very early pathophysiology of AD and distinguish it from disorders with similar symptomatology, such as other types of dementia and major depression. The sensitivity and specificity of these biomarkers in combination with clinical assessment should be of at least 90%.
2. 2.Enable prediction of the course of events of the disease, such as the disease rate in individual patients. Biomarkers that can predict the pattern of future symptoms will be extremely valuable.
3. 3.Allow monitoring of early effects of new disease-modifying therapies (so-called surrogate biomarkers). Currently clinical therapeutic trials for AD require large patient groups together with long-term treatment. Both size of the groups and treatment time will be reduced with the help of surrogate biomarkers.
4. 4.Study the pathogenesis of the disease. Biomarkers can be used to investigate in detail early alterations in AD patients. For instance, changes in the levels of certain molecules in CSF together with genetic predisposition could then be correlated to clinical signs and changes detectable by brain imaging. This can lead to identification of new therapeutic targets that could easily be monitored in future trials.

Conditions

Mild Cognitive Impairment; Alzheimer's Disease; Dementia With Lewy Bodies; Vascular Dementia

Outcome Measures

Primary Outcomes (1)

• To compare the time to conversion to clinically probable AD in MCI subjects or healthy elderly subjects with normal and abnormal biomarkers (CSF, blood, MRI, PET)

  Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 4-6 years after baseline.

Secondary Outcomes (6)

• Rate of cognitive decline as measured by various cognitive tests, Activities of Daily Living (FAQ) and Global Deterioration Scale.

  Time zero equals the baseline visit. All subjects will subsequently attend follow-up visits every year for approximately 10 years after baseline.

• Group differences for imaging and wet biomarker measurements.

  At baseline, 1 years, 2 years, 3 years, 4 years, 6 years, 8 years and 10 years.

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

  At baseline, 1 years, 2 years, 3 years, 4 years, 6 years, 8 years and 10 years.

• Rates of change on each specified biochemical biomarker

  At baseline, 1 years, 2 years, 3 years, 4 years, 6 years, 8 years and 10 years.

• Correlations between biomarkers and biomarker change

  At baseline, 1 years, 2 years, 3 years, 4 years, 6 years, 8 years and 10 years.

Study Arms (2)

Mild cognitive impairment

550 patients with mild cognitive impairment or subjective cognitive symptoms at baseline.

Healthy elderly subjects

650 elderly subjects, who are cognitively healthy at baseline.

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Community sample

You may qualify if:

• Healthy elderly subjects
• No cognitive symptoms reported by patient and/or informant
• Normal performance on cognitive tests
• General cognition and functional performance preserved such that a diagnosis of MCI or dementia cannot be made by physician at the time of the baseline visit
• Between 60 and 90 years of age
• Fluent in Swedish
• Agrees to at least one lumbar puncture, and neuropsychological testing.
• Mild cognitive impairment
• Cognitive symptoms reported by patient and/or informant
• Between 60 and 80 years of age
• Mini-Mental State Exam score between 24 and 30
• General cognition and functional performance sufficiently preserved such that a diagnosis of dementia cannot be made by physician at the time of the baseline visit
• Fluent in Swedish
• Agrees to at least one lumbar puncture, and neuropsychological testing.

You may not qualify if:

• Any significant neurologic disease other than dementia disorders, such as Huntington's disease, normal pressure hydrocephalus, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities.
• Major depression as described in DSM-IV.
• History of schizophrenia or other recurrent psychotic disorder
• History of alcohol or substance abuse or dependence within the past 5 years

Sponsors & Collaborators

• Skane University Hospital: lead
• Lund University: collaborator

Study Sites (2)

Memory Clinic, Hospital of Ängelholm

Ängelholm, Sweden

Location

Memory Clinic, Skåne University Hospital

Malmo, 20502, Sweden

Location

Related Publications (26)

• Hansson O, Janelidze S, Hall S, Magdalinou N, Lees AJ, Andreasson U, Norgren N, Linder J, Forsgren L, Constantinescu R, Zetterberg H, Blennow K; Swedish BioFINDER study. Blood-based NfL: A biomarker for differential diagnosis of parkinsonian disorder. Neurology. 2017 Mar 7;88(10):930-937. doi: 10.1212/WNL.0000000000003680. Epub 2017 Feb 8.

  PMID: 28179466 BACKGROUND

• Janelidze S, Hertze J, Nagga K, Nilsson K, Nilsson C; Swedish BioFINDER Study Group; Wennstrom M, van Westen D, Blennow K, Zetterberg H, Hansson O. Increased blood-brain barrier permeability is associated with dementia and diabetes but not amyloid pathology or APOE genotype. Neurobiol Aging. 2017 Mar;51:104-112. doi: 10.1016/j.neurobiolaging.2016.11.017. Epub 2016 Dec 5.

  PMID: 28061383 BACKGROUND

• Smith R, Scholl M, Honer M, Nilsson CF, Englund E, Hansson O. Tau neuropathology correlates with FDG-PET, but not AV-1451-PET, in progressive supranuclear palsy. Acta Neuropathol. 2017 Jan;133(1):149-151. doi: 10.1007/s00401-016-1650-1. Epub 2016 Nov 29. No abstract available.

  PMID: 27900460 BACKGROUND

• Mattsson N, Zetterberg H, Janelidze S, Insel PS, Andreasson U, Stomrud E, Palmqvist S, Baker D, Tan Hehir CA, Jeromin A, Hanlon D, Song L, Shaw LM, Trojanowski JQ, Weiner MW, Hansson O, Blennow K; ADNI Investigators. Plasma tau in Alzheimer disease. Neurology. 2016 Oct 25;87(17):1827-1835. doi: 10.1212/WNL.0000000000003246. Epub 2016 Sep 30.

  PMID: 27694257 BACKGROUND

• Hahn A, Schain M, Erlandsson M, Sjolin P, James GM, Strandberg OT, Hagerstrom D, Lanzenberger R, Jogi J, Olsson TG, Smith R, Hansson O. Modeling Strategies for Quantification of In Vivo 18F-AV-1451 Binding in Patients with Tau Pathology. J Nucl Med. 2017 Apr;58(4):623-631. doi: 10.2967/jnumed.116.174508. Epub 2016 Oct 20.

  PMID: 27765859 BACKGROUND

• Smith R, Schain M, Nilsson C, Strandberg O, Olsson T, Hagerstrom D, Jogi J, Borroni E, Scholl M, Honer M, Hansson O. Increased basal ganglia binding of 18 F-AV-1451 in patients with progressive supranuclear palsy. Mov Disord. 2017 Jan;32(1):108-114. doi: 10.1002/mds.26813. Epub 2016 Oct 6.

  PMID: 27709757 BACKGROUND

• Smith R, Puschmann A, Scholl M, Ohlsson T, van Swieten J, Honer M, Englund E, Hansson O. 18F-AV-1451 tau PET imaging correlates strongly with tau neuropathology in MAPT mutation carriers. Brain. 2016 Sep;139(Pt 9):2372-9. doi: 10.1093/brain/aww163. Epub 2016 Jun 29.

  PMID: 27357347 BACKGROUND

• Surova Y, Lampinen B, Nilsson M, Latt J, Hall S, Widner H; Swedish BioFINDER study; van Westen D, Hansson O. Alterations of Diffusion Kurtosis and Neurite Density Measures in Deep Grey Matter and White Matter in Parkinson's Disease. PLoS One. 2016 Jun 30;11(6):e0157755. doi: 10.1371/journal.pone.0157755. eCollection 2016.

  PMID: 27362763 BACKGROUND

• Pannee J, Portelius E, Minthon L, Gobom J, Andreasson U, Zetterberg H, Hansson O, Blennow K. Reference measurement procedure for CSF amyloid beta (Abeta)1-42 and the CSF Abeta1-42 /Abeta1-40 ratio - a cross-validation study against amyloid PET. J Neurochem. 2016 Nov;139(4):651-658. doi: 10.1111/jnc.13838. Epub 2016 Sep 30.

  PMID: 27579672 BACKGROUND

• Janelidze S, Stomrud E, Palmqvist S, Zetterberg H, van Westen D, Jeromin A, Song L, Hanlon D, Tan Hehir CA, Baker D, Blennow K, Hansson O. Plasma beta-amyloid in Alzheimer's disease and vascular disease. Sci Rep. 2016 May 31;6:26801. doi: 10.1038/srep26801.

  PMID: 27241045 BACKGROUND

• van Westen D, Lindqvist D, Blennow K, Minthon L, Nagga K, Stomrud E, Zetterberg H, Hansson O. Cerebral white matter lesions - associations with Abeta isoforms and amyloid PET. Sci Rep. 2016 Feb 9;6:20709. doi: 10.1038/srep20709.

  PMID: 26856756 BACKGROUND

• Smith R, Wibom M, Olsson T, Hagerstrom D, Jogi J, Rabinovici GD, Hansson O. Posterior Accumulation of Tau and Concordant Hypometabolism in an Early-Onset Alzheimer's Disease Patient with Presenilin-1 Mutation. J Alzheimers Dis. 2016;51(2):339-43. doi: 10.3233/JAD-151004.

  PMID: 26836192 BACKGROUND

• Hall S, Surova Y, Ohrfelt A; Swedish BioFINDER Study; Blennow K, Zetterberg H, Hansson O. Longitudinal Measurements of Cerebrospinal Fluid Biomarkers in Parkinson's Disease. Mov Disord. 2016 Jun;31(6):898-905. doi: 10.1002/mds.26578. Epub 2016 Feb 16.

  PMID: 26878815 BACKGROUND

• Voevodskaya O, Sundgren PC, Strandberg O, Zetterberg H, Minthon L, Blennow K, Wahlund LO, Westman E, Hansson O; Swedish BioFINDER study group. Myo-inositol changes precede amyloid pathology and relate to APOE genotype in Alzheimer disease. Neurology. 2016 May 10;86(19):1754-61. doi: 10.1212/WNL.0000000000002672. Epub 2016 Apr 15.

  PMID: 27164711 BACKGROUND

• Janelidze S, Zetterberg H, Mattsson N, Palmqvist S, Vanderstichele H, Lindberg O, van Westen D, Stomrud E, Minthon L, Blennow K; Swedish BioFINDER study group; Hansson O. CSF Abeta42/Abeta40 and Abeta42/Abeta38 ratios: better diagnostic markers of Alzheimer disease. Ann Clin Transl Neurol. 2016 Jan 1;3(3):154-65. doi: 10.1002/acn3.274. eCollection 2016 Mar.

  PMID: 27042676 BACKGROUND

• Palmqvist S, Zetterberg H, Mattsson N, Johansson P; Alzheimer's Disease Neuroimaging Initiative; Minthon L, Blennow K, Olsson M, Hansson O; Swedish BioFINDER Study Group. Detailed comparison of amyloid PET and CSF biomarkers for identifying early Alzheimer disease. Neurology. 2015 Oct 6;85(14):1240-9. doi: 10.1212/WNL.0000000000001991. Epub 2015 Sep 9.

  PMID: 26354982 BACKGROUND

• Lindqvist D, Prokopenko I, Londos E, Middleton L, Hansson O. Associations between TOMM40 Poly-T Repeat Variants and Dementia in Cases with Parkinsonism. J Parkinsons Dis. 2016;6(1):99-108. doi: 10.3233/JPD-150693.

  PMID: 26756745 BACKGROUND

• Gustavsson AM, Stomrud E, Abul-Kasim K, Minthon L, Nilsson PM, Hansson O, Nagga K. Cerebral Microbleeds and White Matter Hyperintensities in Cognitively Healthy Elderly: A Cross-Sectional Cohort Study Evaluating the Effect of Arterial Stiffness. Cerebrovasc Dis Extra. 2015 May 20;5(2):41-51. doi: 10.1159/000377710. eCollection 2015 May-Aug.

  PMID: 26120319 BACKGROUND

• Hall S, Surova Y, Ohrfelt A, Zetterberg H, Lindqvist D, Hansson O. CSF biomarkers and clinical progression of Parkinson disease. Neurology. 2015 Jan 6;84(1):57-63. doi: 10.1212/WNL.0000000000001098. Epub 2014 Nov 19.

  PMID: 25411441 BACKGROUND

• Palmqvist S, Zetterberg H, Blennow K, Vestberg S, Andreasson U, Brooks DJ, Owenius R, Hagerstrom D, Wollmer P, Minthon L, Hansson O. Accuracy of brain amyloid detection in clinical practice using cerebrospinal fluid beta-amyloid 42: a cross-validation study against amyloid positron emission tomography. JAMA Neurol. 2014 Oct;71(10):1282-9. doi: 10.1001/jamaneurol.2014.1358.

  PMID: 25155658 BACKGROUND

• Lautner R, Palmqvist S, Mattsson N, Andreasson U, Wallin A, Palsson E, Jakobsson J, Herukka SK, Owenius R, Olsson B, Hampel H, Rujescu D, Ewers M, Landen M, Minthon L, Blennow K, Zetterberg H, Hansson O; Alzheimer's Disease Neuroimaging Initiative. Apolipoprotein E genotype and the diagnostic accuracy of cerebrospinal fluid biomarkers for Alzheimer disease. JAMA Psychiatry. 2014 Oct;71(10):1183-91. doi: 10.1001/jamapsychiatry.2014.1060.

  PMID: 25162367 BACKGROUND

• Silajdzic E, Constantinescu R, Holmberg B, Bjorkqvist M, Hansson O. Flt3 ligand does not differentiate between Parkinsonian disorders. Mov Disord. 2014 Sep;29(10):1319-22. doi: 10.1002/mds.25948. Epub 2014 Jul 16.

  PMID: 25044107 BACKGROUND

• Lindqvist D, Hall S, Surova Y, Nielsen HM, Janelidze S, Brundin L, Hansson O. Cerebrospinal fluid inflammatory markers in Parkinson's disease--associations with depression, fatigue, and cognitive impairment. Brain Behav Immun. 2013 Oct;33:183-9. doi: 10.1016/j.bbi.2013.07.007. Epub 2013 Jul 31.

  PMID: 23911592 BACKGROUND

• Surova Y, Szczepankiewicz F, Latt J, Nilsson M, Eriksson B, Leemans A, Hansson O, van Westen D, Nilsson C. Assessment of global and regional diffusion changes along white matter tracts in parkinsonian disorders by MR tractography. PLoS One. 2013 Jun 13;8(6):e66022. doi: 10.1371/journal.pone.0066022. Print 2013.

  PMID: 23785466 BACKGROUND

• Cullen NC, Leuzy A, Palmqvist S, Janelidze S, Stomrud E, Pesini P, Sarasa L, Allue JA, Proctor NK, Zetterberg H, Dage JL, Blennow K, Mattsson-Carlgren N, Hansson O. Individualized prognosis of cognitive decline and dementia in mild cognitive impairment based on plasma biomarker combinations. Nat Aging. 2021 Jan;1(1):114-123. doi: 10.1038/s43587-020-00003-5. Epub 2020 Nov 30.

  PMID: 37117993 DERIVED

• Johansson M, Stomrud E, Johansson PM, Svenningsson A, Palmqvist S, Janelidze S, van Westen D, Mattsson-Carlgren N, Hansson O. Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer's Disease Pathology and Cognitive Decline. Biol Psychiatry. 2022 Jul 1;92(1):34-43. doi: 10.1016/j.biopsych.2022.01.012. Epub 2022 Jan 31.

  PMID: 35346458 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Cerebrospinal fluid, plasma, DNA, mRNA

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease; Lewy Body Disease; Dementia, Vascular

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Cerebrovascular Disorders; Intracranial Arteriosclerosis; Intracranial Arterial Diseases; Leukoencephalopathies; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Oskar Hansson, MD, PhD

  Lund University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., PhD

Study Record Dates

• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: April 27, 2025

Record last verified: 2025-04

Locations

SE (2)