The Swedish BioFINDER - Preclinical AD Study

Study Overview
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Brief Summary
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This research study aims to examine biomarkers of Alzheimer's disease (AD) 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.

Official Title
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The Swedish BioFINDER - Preclinical AD Study

Conditions
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Alzheimer Disease, Mild Cognitive Impairment, Mild Dementia

Intervention / Treatment
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* Diagnostic Test: Plasma tau
* Diagnostic Test: Plasma Ab42/Ab40
* Diagnostic Test: Flutemetamol F18 Injection
* Diagnostic Test: [18F]-RO6958948 Injection
* Diagnostic Test: Magnetic resonance imaging (MRI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 50-80 Individuals aged 50-60 require at least one of the following risk factors for AD: Known APOE-E4 carrier Known 1st degree family history of dementia or severe memory loss with onset prior to 75. Known amyloid brain pathology by either CSF or PET scan. Mini-Mental State Examination (MMSE) ≥26 (aged >65); MMSE ≥27 (aged 50-65). Score of 12 or above on the Montreal Cognitive Assessment (MoCA) telephone version. 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: Fulfils the criteria for minor or major neurocognitive disorder according to The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). 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. Major depression, bipolar disorder, or recurrent psychotic disorders within the past year. History of alcohol and/or substance abuse or dependence within the past year. Significant unstable systemic illness or organ failure, such as terminal cancer, that makes it difficult to participate in the study. Refusing or unable to complete baseline cognitive and biomarker assessments (i.e., cognitive testing, blood draw, MRI and PET).

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cognitively unimpaired individuals with preclinical Alzheimer's disease<br>75% of the recruited population will be cognitively unimpaired individuals with preclinical Alzheimer's disease. | Diagnostic Test: Plasma tau<br>* Plasma levels of different p-tau and np-tau species<br>Diagnostic Test: Plasma Ab42/Ab40<br>* Plasma levels of Ab42/Ab40 ratio<br>Diagnostic Test: Flutemetamol F18 Injection<br>* Positron emission tomography (PET) imaging of amyloid-β plaques<br>Diagnostic Test: [18F]-RO6958948 Injection<br>* PET imaging of Tau aggregates<br>Diagnostic Test: Magnetic resonance imaging (MRI)<br>* Different MRI sequences relevant for brain imaging<br>|
| Cognitively unimpaired individuals without preclinical Alzheimer's disease.<br>25% of the recruited population will be cognitively unimpaired individuals without preclinical Alzheimer's disease. | Diagnostic Test: Plasma tau<br>* Plasma levels of different p-tau and np-tau species<br>Diagnostic Test: Plasma Ab42/Ab40<br>* Plasma levels of Ab42/Ab40 ratio<br>Diagnostic Test: Flutemetamol F18 Injection<br>* Positron emission tomography (PET) imaging of amyloid-β plaques<br>Diagnostic Test: [18F]-RO6958948 Injection<br>* PET imaging of Tau aggregates<br>Diagnostic Test: Magnetic resonance imaging (MRI)<br>* Different MRI sequences relevant for brain imaging<br>|

What is the study measuring?
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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 The Preclinical Alzheimer Cognitive Composite (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 - digital assessment | 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 | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Preclinical Alzheimer, early diagnosis, biomarkers, plasma, CSF, PET