A FinnGen pilot clinical recall study for Alzheimer’s disease

ABSTRACT 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.