The BioFINDER-Primary Care study (NCT06120361; also known as the Alzheimer’s disease detection study “ADetect”) enrolls study participants with cognitive symptoms at more than 20 different primary care centers in southern Sweden in order to improve the diagnostic accuracy of AD and cognitive impairment in primary care settings. Hopefully this will ensure better care and treatment as well as facilitate correct referrals to specialized memory clinics. The investigators strive to recruit diverse and representative populations of patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and mild dementia.
General aims:
- Improve the detection of mild cognitive impairment (MCI) and dementia in primary care. Early detection of cognitive impairment can lead to improved care, optimized treatments, and highlight issues regarding decision making, incorrect utilizations of healthcare resources and driving ability. Despite this, primary care still uses the same tools as 30-40 years ago, which have a low sensitivity for MCI. In this project, the investigators will identify the optimal cognitive screening tests by doing head-to-head comparisons of novel and traditional cognitive tests including computerized tests and smartphone apps that can run daily tests of memory and executive function.
- Develop and evaluate cognitive tests, blood-based biomarkers and brain imaging methods that are suitable for accurate and early diagnosis of Alzheimer’s disease (AD) in primary care. AD is the most common dementia (causing about 70% of all dementia cases) and there are currently 4 registered symptomatic treatments that improve cognition, activities of daily function and may delay the time to nursing homes. Detection of AD is therefore essential in order to start the treatment. Further, promising trials suggest that disease-modifying AD treatments might be available in the future targeting Aβ (the cause and hallmark pathology of AD). In this scenario, it essential that AD is identified at an early stage before neurodegeneration is wide-spread. To tackle this, the investigators will develop and validate methods that can accurately detect people with early AD in a primary care setting, including i) cognitive screening tests (e.g. computerized tests and smartphone apps); ii) novel blood-based biomarkers (e.g. mass spectrometry based plasma p-tau217 and Ab42/40 measures as well as the combination of these two biomarkers in C2N Diagnostics’ PrecivityAD2 test), and iii) widely available brain imaging methods (including a comparison between computed tomography scan [CT] and Magnetic resonance imaging scan [MRI]). The ultimate goal is to develop brief and cost-effective diagnostic algorithms. The investigators will both validate a previous algorithm that the investigators have published as well as test new ones, including the PrecivityAD2 test result known as the Amyloid Probability Score 2 (APS2, ranging from 0-100 for the likelihood of brain amyloid plaques).
- To prospectively validate plasma AD biomarkers for diagnosis of patients with cognitive symptoms who are evaluated in primary care. The investigators here intend to study the clinical robustness and accuracy of plasma AD biomarkers in real-world settings by using high-performing plasma assays over a 2-3 year time period. In this study, plasma samples are collected as part of clinical praxis and analyzed on a bi-weekly basis throughout the study period (and not in single batches). The investigators will (1) use pre-defined cut offs for each biomarker (similar to real world clinical practice), and (2) use an accurate reference standard (i.e., cerebrospinal fluid (CSF)/Positron emission tomography (PET) AD biomarkers). The effects of potential confounders (such as kidney function) on diagnostic accuracy will also be studied. The investigators will only use really top-performing plasma assays for each biomarker including for p-tau217 and Ab42/Ab40.
- Determine whether blood AD biomarkers improve patient management in primary care. As often noted by regulatory authorities, it is important to know if novel diagnostic methods improve the actual management of patients in real world settings. Consequently, the investigators study whether the most promising plasma biomarkers for symptomatic AD (including the APS2) will improve AD diagnosis beyond what is currently done as part of clinical practice. The physician will document the most likely diagnosis (and the certainty of the diagnosis) after having performed an interview with the patient and informant, as well as evaluated the patient’s cognitive test results, routine blood tests and structural brain imaging. The physician will then re-evaluate the diagnosis (and certainty of diagnosis) after having obtained the APS2, plasma p-tau217 and Ab42/Ab40 results, and the pre- and post-test diagnosis will be compared to the reference standard (i.e. presence of AD brain pathology as determined with biomarkers). Change in treatment and care of the patient after evaluating blood-based biomarkers will also be recorded similar to how amyloid-PET was evaluated in the IDEAS study.
