Biomarkers of Cognitive Decline Among Normal Individuals: The Biocard Cohort

Johns Hopkins University, Baltimore MD

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Abstract

PROJECT SUMMARY/ABSTRACT This is an Administrative Supplement for the grant entitled ‘Biomarkers of Cognitive Decline Among Normal Individuals: The BIOCARD Cohort’. The BIOCARD study is a longitudinal study begun in 1995 to examine the preclinical phase of Alzheimer’s disease (AD). All participants were cognitively normal at enrollment (n=349), and primarily middle age (mean age = 56.7 yrs.). The study was initially conducted at the NIH. In 2009, investigators at Johns Hopkins University (JHU) were funded to re-enroll the cohort and continue follow-up. Approximately 93% of the original cohort was re-enrolled at JHU and the duration of follow-up for many of the participants is now 30 years. Enrollment of an additional group of cognitively unimpaired individuals was initiated in 2020, with the goal of increasing the at-risk participants in the study. The total sample size is currently 466. The participants have been characterized longitudinally with comprehensive clinical and cognitive assessments and a wide range of AD biomarkers. Initially, the study procedures included cerebrospinal fluid (CSF) collection, blood draws and magnetic resonance imaging (MRI). As technology evolved over time, amyloid and tau positron emission tomography (PET) scans have been added to the biomarker procedures. A key strength of the study is the substantial number of individuals who have progressed from normal cognition to MCI (n=108). This makes it possible to examine the full ‘preclinical window’, including the years preceding amyloid positivity, as well as the years preceding tau positivity, and the subsequent onset of the symptomatic phase of AD. Thus, the study can address several overarching goals, including: (1) To examine proteomic changes measured in CSF and blood that precede amyloid positivity; (2) To examine novel spatially-specific MRI and Tau PET changes that precede tau positivity; (3) To examine the association between modifiable lifestyle factors and longitudinal proteomic and imaging measures with rate of decline in cognition; and (4) To examine the association of non-AD biomarkers and rate of decline in cognition among those who are AD biomarker positive, as well as those who are AD biomarker negative. It is essential to maintain this unique cohort to not only accomplish these goals, but to also provide a rich resource of cognitive, clinical and biomarker data for the field.