The Swedish BioFINDER - Memory Clinic Study

The diagnosis of diseases causing memory difficulties or dementia is often challenging. Without the use of advanced methods such as cerebrospinal fluid tests, approximately 25-30% do not receive a correct diagnosis today. However, the investigators have recently developed new blood biomarkers with high diagnostic accuracy, and the investigators now want to investigate whether they can eventually replace cerebrospinal fluid tests. This is because blood tests are much more cost-effective and significantly easier for patients compared to cerebrospinal fluid tests.

In this study, 1200 patients undergoing clinical evaluations at the Memory Clinic, Skåne University Hospital in Malmö, are included for blood and cerebrospinal fluid sample collection. The blood samples are sent for analysis using the new blood biomarkers. Subsequently, the results are compared with those from the clinical analysis of cerebrospinal fluid to determine how well they perform in routine clinical practice as an alternative to cerebrospinal fluid tests and whether the blood test improves patient care. This comparison is carried out by the attending physician in three steps:

1. Assessment without access to the results of either the blood test or cerebrospinal fluid test.
2. Assessment with access to only the results of the blood test.
3. Assessment with access to the results of both the blood test and cerebrospinal fluid test.

Aim 1) To prospectively validate plasma AD biomarkers for diagnosis of patients with cognitive symptoms who are evaluated in a specialist memory clinic. 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 2-3 years, focusing on a specialist memory clinic population (n=1200). 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/at study closure). 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., presence of AD brain pathology as determined with cerebrospinal fluid (CSF) Aβ42/Aβ40 [Lumipulse; Fujirebio] and CSF P-tau217 [Eli Lilly]). The investigators will strive to recruit diverse and representative populations of patients with subjective cognitive decline (SCD), mild cognitive impairment (MCI) and mild dementia. 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 p-tau217 and Ab42/Ab40.

Expected outcomes: The investigators will 1) determine the diagnostic accuracy of different plasma AD biomarkers, 2) establish an optimal combination of plasma biomarkers for detection of AD brain pathology and 3) identify the effects of different potential confounding factors (e.g., kidney function) on the performance of different plasma biomarkers, when used prospectively in both real-world specialist and primary care populations.