Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer’s disease (AD). This study describes a process for clinical recall studies from FinnGen. We demonstrate the feasibility to systematically ascertain customized clinical data from FinnGen participants with ICD10 diagnosis of AD or mild cognitive disorder (MCD) in a single-center cross-sectional study testing blood-based biomarkers and cognitive functioning in-person, computer-based and remote. As a result, 19% (27/140) of a pre-specified FinnGen subcohort were successfully recalled and completed the study. Hospital records largely validated registry entries. For 8/12 MCD patients, other reasons than AD were identified as underlying diagnosis. Cognitive measures correlated across platforms, with highest consistencies for dementia screening (r = 0.818) and semantic fluency (r = 0.764), respectively, for in-person versus telephone-administered tests. Glial fibrillary acidic protein (GFAP) (p < 0.002) and phosphorylated-tau 181 (pTau-181) (p < 0.020) most reliably differentiated AD from MCD participants. We conclude that informative, customized clinical recall studies from FinnGen are feasible.
Global emphasis on enhancing prevention and treatment strategies necessitates increased understanding of biological mechanisms of psychopathology. Plasma proteomics is a powerful tool that has been applied in the context of specific mental disorders for biomarker identification. The p-factor, also known as the "general psychopathology factor", is a concept in psychopathology suggesting that there is a common underlying factor that contributes to the development of various forms of mental disorders. It has been proposed that the p-factor can be used to understand the overall mental health status of an individual. Here we aimed to discover plasma proteins associated with the p-factor in 775 young adults in the FinnTwin12 cohort. Using liquid chromatography-tandem mass spectrometry, 14 proteins with a significant connection with the p-factor were identified, 9 of which were linked to epidermal growth factor receptor (EGFR) signalling. This exploratory study provides new insight into biological alterations associated with mental health status in young adults.
Background: Successful development of novel therapies requires that clinical trials are conducted in patient cohorts with the highest benefit-to-risk ratio. Population-based biobanks with comprehensive health and genetic data from large numbers of individuals hold promise to facilitate identification of trial participants, particularly when interventions need to start while symptoms are still mild, such as for Alzheimer's disease (AD). However, few studies have yet tested whether recalling biobank participants into clinical follow-up studies is feasible. Objective: To establish a process for clinical recall studies from FinnGen and demonstrate the feasibility to systematically ascertain customized clinical data from FinnGen participants with ICD10 diagnosis of AD or mild cognitive disorder (MCD). Methods: Single-center cross-sectional study testing blood-based biomarkers and cognitive functioning in-person, computer-based and remote. Results: 19% (27/140) of a pre-specified FinnGen subcohort were successfully recalled and completed the study. Hospital records largely validated registry entries. For 8/12 MCD patients, other reasons than AD were identified as underlying diagnosis. Cognitive measures correlated across platforms, with highest consistencies for dementia screening (r=0.818) and semantic fluency (r=0.764), respectively, for in-person versus telephone-administered tests. GFAP (p<0.002) and pTau-181 (p<0.020) most reliably differentiated AD from MCD participants. Conclusions: Informative, customized clinical recall studies from FinnGen are feasible.
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