The Swedish BioFINDER Sleep Study

BioFINDER-Sleep: Idiopathic REM-sleep Behavior Disorder & Early Parkinson's Disease

BioFINDER-Sleep study was established in 2021 and will include patients with early Parkinson´s disease (PD) and persons with iRBD to provide essential insights into the underlying mechanisms of the progressive neurodegenerative processes in central and peripheral nervous systems. Briefly polysomnography will be used to establish the presence of RBD in both the early PD cohort and in the iRBD cohort. Then, state of the art multimodal imaging techniques will be used, including, magnetic resonance imaging (MRI), positron emission tomography (PET) of the dopamine transporters (DAT-PET) to quantify dopamine terminal loss, and [123I] MIBG scintigraphy of the heart will be performed to quantify the loss noradrenaline terminals to the heart. In addition to this, synuclein seed amplification assays (SSAs) will be applied to cerebrospinal fluid (CSF) and skin samples to establish synuclein pathology status. Further, CSF and blood biomarkers will be developed that can be used to as prognostic markers. These investigations will be done in parallel to clinical assessments of motor and non-motor symptoms as well as assessment of cognitive function in a longitudinal setting.

Study Overview

• Status: Recruiting
• Conditions: Synucleinopathies; Lewy Body Disease; Parkinson´s Disease; Synucleinopathy; REM Sleep Behavior Disorder (iRBD)
• Intervention / Treatment: Diagnostic test: Dopamine transporter PET scan with [18F]FE-PE2I; Diagnostic test: Magnetic resonance imaging (MRI); Diagnostic test: [123I] MIBG scintigraphy of the heart; Diagnostic test: α-synuclein seeding amplification assays; Diagnostic test: Polysomnography; Diagnostic test: Smell test

Detailed Description

General aims:

The setup enables the study to test several hypotheses concerning the relation between neurodegenerative disorders and RBD. Here, the main specific aims are summarized:

1. Patients with early PD will be recruited to estimate the frequency of concomitant RBD in this cohort at the time of diagnosis as well as at follow-up. The longitudinal setup enables the study to test the claim that early PD patients with concomitant RBD represent a more severe subtype of PD and whether this is reflected in blood, CSF or imaging biomarkers that are collected longitudinally.
2. Persons with iRBD represent an important prodromal stage of parkinsonian disorders and are included here to study changes in clinical symptoms, blood and CSF biomarkers, imaging modalities over time to better understand the earliest symptomatic phases of these neurodegenerative disorders.
3. Collected multimodal biomarkers longitudinally enables the study to investigate whether co-pathologies, like presence of Alzheimer's disease pathology, affect the clinical and biomarker trajectories over time in people with prodromal or early PD.
4. Minor motor symptoms are considered a general characteristic of synucleinopathies, even in prodromal stages. However, clinical scales used in regular neurological examination may not be sensitive to subtle worsening of minor motor symptoms. Therefore, a setup will be implemented to characterize motor function in the cohort using GAITRite® and the Mobility Lab®. In addition to this, patients are asked to download an app (Roche-PD app) on their mobile phones where weekly tests of motor function and cognitive function allow for continuous monitoring of progression of symptoms. This setup will allow the study to develop clinically meaningful markers of disease.

Study plan:

Patient population:

The study plan to recruit early PD patients, persons with iRBD as well as healthy controls to participate in the current study. Early PD patients will be recruited from the Memory Clinic at Skåne University Hospital as well as private or public Neurology clinics within Region Skåne. Persons with iRBD will be recruited to participate in the study through advertisements in relevant media and in collaboration with private and public Sleep clinics that perform diagnostic sleep studies. Healthy controls will be recruited through advertisements.

Clinical assessments:

All subjects included in this study will undergo a standardized clinical assessment and fill out questionnaires as instructed by the nurse or doctor associated with the project.

Symptoms of Parkinson´s disease will be evaluated using the MDS-UPDRS as well as assessment of Hoehn & Yahr stages. Subtle motor symptoms will be examined by the use of Purdue PEG board, and alternate tapping test and the 3-m time up and go test. Questionnaires will be used to reveal the presence of non-motor symptoms, including the presence of autonomic dysfunction. Objective measurement of orthostatic hypotension is included in the clinical assessment. Hyposmia or anosmia will be quantified with Sniffin' Sticks test. The clinical assessment will be performed at baseline, and after 18, 36, 54 and 72 months to allow for detection of conversion to an established parkinsonian disorder. All follow-ups include a more in-depth evaluation of motor symptoms by a physical therapist.

PET imaging:

[18F]FE-PE2I is a highly selective imaging ligand for the assessment of dopamine transporters and provide an indirect measure of surviving dopaminergic neurons. Briefly, 185 MBq [18F]FE-PE2I will be injected intravenously and a static PET scan of 30 min will be performed on GE Discovery MI PET-CT cameras, starting 15 min post injection. [18F]FE-PE2I will be repeated at follow-up at 3 and 6 years after baseline.

MIBG scintigraphy:

Early and late images of the thorax will be collected for 15 minutes, 15 and 210 minutes after the administration of 110 MBq [123I] MIBG, respectively. Images will be collected on a SPECT-gamma camera to estimate the mean heart-uptake/mean mediastinum-uptake ratios and to estimate washout rates as the differences of mean uptake in early and late images. A low dose SPECT/CT is performed after the late images. [123I] MIBG scintigraphy will be repeated at follow-up at 3 and 6 years after baseline.

Magnetic resonance imaging; 3 Tesla Magnetic resonance imaging (MRI) scans will be done in all study cohorts on a 3T Siemens MAGNETOM Prisma scanner. A wide variety of MRI techniques will be used to study regional brain volume (three-dimensional magnetization-prepared rapid acquisition with gradient echo (3D MPRAGE)), metabolism (MR spectroscopy (MRS)), structural and functional connectivity of different brain regions (diffusion tensor imaging (DTI) and functional MRI (fMRI)), regional blood flow (arterial spin labeling (ASL)), iron deposition (susceptibility-weighted imaging (SWI)) and the presence of small vessel disease (MPRAGE, SWI and fluid-attenuated inversion recovery (FLAIR)) as well as neuromelanin sensitive sequences that can be used as an indirect measure of dopaminergic and noradrenergic terminals. The protocol will take approximately 60 min to perform. No contrast-enhancing agent will be used. MRI will be repeated at follow-up at 3 and 6 years after baseline.

Polysomnography The examination will take place during a separate study visit that includes a stay overnight at the hospital. A complete setup of the polysomnography will be performed according to the requirements of American Academy of Sleep Medicine to detect REM-sleep without atonia and compliant with the recommendations by the International REM Sleep Behavior Disorder Disorder Study Group (IRBDSG).

Digital assessments of motor and cognitive performance. In a subset of study participants motor and cognitive function will be assessed using an application on a smartphone (Roche PD App). The assessments will include active tasks as well as passive tasks to evaluate both motor and cognitive performance.

Cerebrospinal fluid and plasma sampling Lumbar CSF samples will be collected in all cohorts according to a standardized protocol in line with clinical standards. In short, lumbar puncture will be done between 9-12 am. 25 ml of CSF will be collected in Low Binding polypropylene tubes, which are stored on ice for 5-20 min until the CSF samples will be centrifuged (2000g, +4°C, 10 min). Thereafter, the CSF will be aliquoted in ca 1 ml portions into Low Binding polypropylene tubes followed by storage at -80°C until batch analyses.

Plasma collection will be done at the same visit as the lumbar puncture. Approximately 60ml blood will be drawn into tubes containing either EDTA (5 x 6 ml tubes) or Lithium heparin (3 x 3 ml tubes) as anticoagulant. After centrifugation (2000g, +4°C, 10 min), plasma samples will be aliquoted into polypropylene tubes and stored at -80°C pending biochemical analyses. Further, EDTA-blood (2 x 6 ml) will also be obtained for genetic DNA analyses and PAX tubes (2 x 2,5 ml) will be frozen without any centrifugation or aliquoting for future RNA analyses.

Fluid sampling will be repeated at follow-up at 3 and 6 years after baseline.

Skin biopsy In the current study, skin biopsies are taken using a 3 mm punch biopsy methodology. A total of four biopsies will be collected from the paravertebral areas on both sides at the level of C7-C8 and an area on one of the legs, 10 cm proximal to the knee. Skin biopsy will be repeated at follow-up at 3 and 6 years after baseline, with the possibility of additional two biopsy collections if needed.

Detailed motor assessments (physical therapist) The assessments mainly address level of physical activity, activity avoidance, gait- and balance problems (including falls and fear of falling) as well as dual task performance, i.e. combining a motor and a cognitive task. The data collection consists of self-administered questionnaires, interview administered questions, clinical assessments as well using objective measures (i.e. using an electronic walkway or using six wearable sensors while conducting some of the tests). Detailed motor assessment by physical therapist will be repeated at follow-up at 3 and 6 years after baseline.

• Study Type: Observational
• Enrollment (Estimated): 650

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: Adjmal Nahimi, MD, PhD; Phone Number: +46 40 33 10 00; Email: adjmal.nahimi@med.lu.se

Study Locations

• Sweden
  • Malmo, Sweden, 392 33
    • Recruiting
    • Skåne University Hospital
    • Contact: Erik Stomrud, MD, PhD; Phone Number: +46 40 33 10 00; Email: erik.stomrud@med.lu.se
    • Contact: Adjmal Nahimi, MD, PhD; Phone Number: +46 40 33 10 00; Email: adjmal.nahimi@med.lu.se

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Individuals with iRBD: Community-based, not restricted to geographical location. But fluency in Swedish and availability to attend repeated visits over the course of 72 months at the site in Malmö, Sweden, is required.

Early Parkinson's disease: Patient from the Neurologic clinic at Skåne University Hospital, Sweden. Also patients from other neurological clinics in the county of Skåne, Sweden.

Healthy controls: Community-based in the surroundings of Skåne University Hospital, Sweden.

Description

Inclusion Criteria:

Idiopathic RBD:

• Polysomnography verified RBD according to AASM criteria.
• Does not fulfill diagnostic criteria for idiopathic Parkinson´s disease.
• Age range 50-100. Women who are <55 years of age will be required to take a pregnancy test before participation in the PET and scintigraphy part of the study if not post-menopausal.
• Ability to give informed consent.
• 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.

Early Parkinson´s disease:

• Fulfills the diagnostic criteria for idiopathic Parkinson´s disease.
• The PD patients will be de novo (yet without any PD treatment) or with treatment for a maximum of 3 years.
• Age range 50-100. Women who are <55 years of age will be required to take a pregnancy test before participation in the PET and scintigraphy part of the study if not post-menopausal.
• Ability to give informed consent.
• Speaks Swedish fluently as stated above. Healthy Controls
• Age range 50-100. Women who are <55 years of age will be required to take a pregnancy test before participation in the PET and scintigraphy part of the study if not post-menopausal.
• No diagnosis of PD or another significant neurological disorder.
• No diagnosis of RBD.
• Ability to give informed consent.
• Speaks Swedish fluently as stated above.

Exclusion Criteria:

For all groups:

• Past history of severe or repeated concussive head injury or stroke or any significant systemic disease or unstable medical condition.
• History of severe and unstable depression, schizophrenia, schizoaffective disorder or bipolar disorder.
• Significant white matter microvascular disease.
• Contraindication to MRI and PET.

Exclusion criteria specific for early Parkinson´s disease:

• Normal dopamine transporter ([18F]FE-PE2I) scan.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Idiopathic REM-sleep Behavior Disorder (iRBD); 200 individuals with iRBD will be recruited through advertisement or due to being under clinical investigation for the condition at any clinic in the county of Skåne, Sweden.	Diagnostic test: Dopamine transporter PET scan with [18F]FE-PE2I; Positron emission tomography (PET) imaging of dopamine transporters (DAT-PET) to quantify dopamine terminal loss.; Diagnostic test: Magnetic resonance imaging (MRI); Different MRI sequences relevant for brain imaging and with focus on dopamine associated structures of the brain.; Diagnostic test: [123I] MIBG scintigraphy of the heart; MIBG scintigraphy to quantify the loss noradrenaline terminals to the heart.; Diagnostic test: α-synuclein seeding amplification assays; synuclein seed amplification assays (SSAs) will be applied to cerebrospinal fluid (CSF) and skin samples to establish synuclein pathology status; Other Names: αSyn-SAA; Diagnostic test: Polysomnography; Polysomnography to establish presence of REM-sleep behavior disorder; Diagnostic test: Smell test; Sniffin' Sticks test to quantify hyposmia or anosmia.; Other Names: Sniffin' Sticks test
Early Parkinson´s disease; 200 patients with early Parkinson's disease will be recruited from the Neurology clinic at Skåne University Hospital and in addition other Neurology clinics in the county of Skåne, Sweden.	Diagnostic test: Dopamine transporter PET scan with [18F]FE-PE2I; Positron emission tomography (PET) imaging of dopamine transporters (DAT-PET) to quantify dopamine terminal loss.; Diagnostic test: Magnetic resonance imaging (MRI); Different MRI sequences relevant for brain imaging and with focus on dopamine associated structures of the brain.; Diagnostic test: [123I] MIBG scintigraphy of the heart; MIBG scintigraphy to quantify the loss noradrenaline terminals to the heart.; Diagnostic test: α-synuclein seeding amplification assays; synuclein seed amplification assays (SSAs) will be applied to cerebrospinal fluid (CSF) and skin samples to establish synuclein pathology status; Other Names: αSyn-SAA; Diagnostic test: Polysomnography; Polysomnography to establish presence of REM-sleep behavior disorder; Diagnostic test: Smell test; Sniffin' Sticks test to quantify hyposmia or anosmia.; Other Names: Sniffin' Sticks test
Healthy controls; 250 healthy controls will be recruited through advertisement and by personal invitation by mail.	Diagnostic test: Dopamine transporter PET scan with [18F]FE-PE2I; Positron emission tomography (PET) imaging of dopamine transporters (DAT-PET) to quantify dopamine terminal loss.; Diagnostic test: Magnetic resonance imaging (MRI); Different MRI sequences relevant for brain imaging and with focus on dopamine associated structures of the brain.; Diagnostic test: [123I] MIBG scintigraphy of the heart; MIBG scintigraphy to quantify the loss noradrenaline terminals to the heart.; Diagnostic test: α-synuclein seeding amplification assays; synuclein seed amplification assays (SSAs) will be applied to cerebrospinal fluid (CSF) and skin samples to establish synuclein pathology status; Other Names: αSyn-SAA; Diagnostic test: Polysomnography; Polysomnography to establish presence of REM-sleep behavior disorder; Diagnostic test: Smell test; Sniffin' Sticks test to quantify hyposmia or anosmia.; Other Names: Sniffin' Sticks test

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Longitudinal Changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Will be evaluated at each follow-up visit every 18 months. The MDS-UPDRS is a clinical rating tool used to assess both motor and non-motor symptoms of Parkinson's disease, as well as their effect on activities of daily living. It is divided into 4 subparts and cotains questions and clinical evaluations. Part 1 and 2 each contain 13 questions. Each question is scored from 0 to 4, where higher scores indicate more severe symptoms. The maximum score for each of these parts is 52. Part 3 is a clinical examination of motor symptoms. It includes 33 items, also scored from 0 to 4. The maximum score for this section is 132. Part 4 assesses motor complications and contains 6 items, scored from 0 to 4. The maximum score for this part is 24"	From baseline to the end of follow-up 72 months later
Longitudinal Changes in Mini-Mental State Examination (MMSE)	Will be evaluated at each follow-up visit every 18 months. MMSE screens for cognitive impairment and score from 0-30 points where higher points indicate better cognitive function.	From baseline to the end of follow-up 72 months later
Time to phenoconversion from iRBD to manifest parkinsonian disorders	Time to phenoconversion from diagnosis of iRBD to manifestation of a parkinsonian disorders according to clinical diagnostic criteria as evaluated at consensus group decision at the last visit.	From baseline to the end of follow-up 72 months later

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation of changes in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) to imaging and fluid biomarkers	Will be evaluated at each follow-up visit every 18 months. The MDS-UPDRS is a clinical rating tool used to assess both motor and non-motor symptoms of Parkinson's disease, as well as their effect on activities of daily living. It is divided into 4 subparts and cotains questions and clinical evaluations. Part 1 and 2 each contain 13 questions. Each question is scored from 0 to 4, where higher scores indicate more severe symptoms. The maximum score for each of these parts is 52. Part 3 is a clinical examination of motor symptoms. It includes 33 items, also scored from 0 to 4. The maximum score for this section is 132. Part 4 assesses motor complications and contains 6 items, scored from 0 to 4. The maximum score for this part is 24"	From baseline to the end of follow-up 72 months later
Correlation of changes in Mini-Mental State Examination (MMSE) to imaging and fluid biomarkers	Will be evaluated at each follow-up visit every 18 months. MMSE screens for cognitive impairment and score from 0-30 points where higher points indicate better cognitive function.	From baseline to the end of follow-up 72 months later.
Correlation between objective testing of motor function by clinician and digital biomarkers of motor function		From baseline to the end of follow-up 72 months later

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): October 1, 2021
• Primary Completion (Estimated): June 1, 2033
• Study Completion (Estimated): June 1, 2033

Study Registration Dates

• First Submitted: April 1, 2026
• First Submitted That Met QC Criteria: April 9, 2026
• First Posted (Actual): April 16, 2026

Study Record Updates

• Last Update Posted (Actual): April 16, 2026
• Last Update Submitted That Met QC Criteria: April 9, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: MRI; PET; Polysomnography; α-synuclein; Plasma; CSF; Early diagnosis; MIBG; UPDRS; cognitive test; DAT PET; Smell test; synuclein seed amplification assays; Motoric test
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Metabolic Diseases; Neurocognitive Disorders; Dementia; Neurodegenerative Diseases; Sleep Wake Disorders; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Proteostasis Deficiencies; Parasomnias; REM Sleep Parasomnias; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Synucleinopathies; Disease; Parkinson Disease; Lewy Body Disease; REM Sleep Behavior Disorder; Parkinson Disease 4, Autosomal Dominant Lewy Body; Diagnostic Techniques and Procedures; Diagnosis; Tomography; Diagnostic Imaging; Monitoring, Physiologic; Magnetic Resonance Imaging; Polysomnography
• Other Study ID Numbers: BioFINDER-sleep

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No