The Swedish BioFINDER 2 Study (BioFINDER2)
Dementia, Alzheimer Disease, Parkinson Disease
About this trial
This is an interventional diagnostic trial for Dementia focused on measuring Early diagnosis, biomarker, PET, MRI, β-amyloid, tau, CSF, cognitive test
Eligibility Criteria
COHORT A: Cognitively healthy younger individuals (40-65 years of age) INCLUSION CRITERIA
- 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.
EXCLUSION CRITERIA
- 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.
COHORT B: Cognitively healthy elderly individuals (66-100 years of age) INCLUSION CRITERIA
- 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.
EXCLUSION CRITERIA
- 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.
COHORT C: Subjective cognitive decline and mild cognitive impairment INCLUSION CRITERIA
- 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.
- MMSE score of 24 - 30 points.
- Do not fulfill the criteria for any dementia (major neurocognitive disorder) according to DSM-V.
- The medical doctor (after clinical assessments, cognitive testing, CSF analyses and structural brain imaging) believes the cognitive complaints are caused by an incipient neurocognitive disorder of any sort. This is defined as any case fulfilling the criteria above (i.e. both SCD and MCI) with an abnormal CSF Aβ42/40 ratio, which is strongly associated with brain Aβ pathology and prodromal Alzheimer's disease. Further, cases with MCI (=minor neurocognitive impairment) due to either Parkinson's disease, Lewy body disease, vascular neurocognitive disorder or frontotemporal dementia (please see Appendix below for clinical criteria and references) can also be included.
- 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.
EXCLUSION CRITERIA
- 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.
- Refusing lumbar puncture, MRI or PET.
COHORT D: Dementia due to Alzheimer's disease INCLUSION CRITERIA
- 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 or psychomotor complaints.
- MMSE score of 12-26 points.
- Fulfill the criteria for dementia (major neurocognitive disorder) due to Alzheimer's disease (DSM-V).
- Speaks and understands Swedish to the extent that an interpreter was not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- 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.
- Refusing lumbar puncture, MRI or PET.
COHORT E: Other dementias INCLUSION CRITERIA
- Age 40-100 years.
- Fulfill the criteria for dementia (major neurocognitive disorder) due to FTD, PDD, DLB or subcortical VaD alternatively the criteria for PD, PSP, MSA or CBS.
- Speaks and understands Swedish to the extent that an interpreter was not necessary for the patient to fully understand the study information and cognitive tests.
EXCLUSION CRITERIA
- 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.
- Refusing lumbar puncture, MRI or PET.
Sites / Locations
- Memory Clinic, Skåne University HospitalRecruiting
- Memory Clinic, Hospital of Ängelholm
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Other
Other
Other
Other
Other
COHORT A: Cognitively healthy younger individuals (40-65 y)
COHORT B: Cognitively healthy elderly individuals (66-100 y)
COHORT C: SCD and MCI
COHORT D: Dementia due to Alzheimer's disease
COHORT E: Other dementias
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.
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.
550 patients with either subjective cognitive decline or mild cognitive impairment 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, all cases with evidence of brain amyloid pathology (i.e. an abnormal CSF Aβ42/40 ratio) will be included. FOLLOW-UP FOR 6 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 every 2 years. Amyloid PET will be performed at baseline and after 4 years. 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.
300 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 50 cases aged 40-65 years of age, 200 cases aged 66-79 years of age and 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 (depends on further funding) and MRI will be done at baseline and after 2 years. No Amyloid PET in this group.
Patients with primary neurodegenerative disorders other than Alzheimer's disease will be recruited: 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). 50 cases with subcortical Vascular dementia (VaD). 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.