Associations Between Plasma, Imaging, Cerebrospinal Fluid Biomarkers and Naturalistic Driving Behaviors, Cognitive Tests Among Cognitively Normal Persons

Abstract

AbstractBackgroundPrevious work indicates that imaging and cerebrospinal fluid (CSF) amyloid and tau biomarkers are associated with driving behaviors, and that driving behaviors can be used to identify preclinical Alzheimer’s disease (AD). Along with traditional biomarkers, we examined the extent to which newer plasma and CSF biomarker are related to driving and cognitive metrics among cognitively normal older drivers.MethodMean driving and cognitive metrics were computed for all available time points in cognitively normal (Clinical Dementia Rating ® = 0) participants (N=167, mean age=73.3±4.9). Participants had a data logger installed in their personal vehicles and drove at their discretion for at least 6 months (mean follow‐up 2.2y±0.9y, range=0.6y‐4.7y) between 6/2/2015 and 2/29/2020 (pre‐COVID data) and took part in cognitive testing yearly. Participants took part in biomarker testing including, imaging (positron emission tomography [PET] amyloid, PET tau, normalized hippocampal volume [nHV]), CSF (Aβ42, Aβ40, tau, ptau181, neurofilament light chain [NfL]), and/or plasma (Aβ42, Aβ40, Aβ42/Aβ40, NfL) within 2 years of data logger installation. Fisher’s Z transformation was used to examine the correlations between the biomarker variables and the driving and cognitive measures.Results(Figure attached) Individual biomarkers were differentially related to different driving behaviors (e.g., number of trips was associated with PET amyloid [p<0.035], plasma Aβ42 [p<0.012] and Aβ40 [p<0.004], but not the other imaging, CSF, and plasma biomarkers [p>0.275]); and to different cognitive scores (e.g., Montreal Cognitive Assessment [MoCA] total scores were associated with amyloid imaging [p<.026], nHV [p<0.033], and plasma Aβ42/Aβ40 [p<0.035] but to no other biomarkers [p>0.080]). Some biomarkers were associated with driving behaviors but not cognitive scores (e.g., CSF Aβ40, tau, NfL; plasma Aβ42 and Aβ40 considered separately) whereas others were related to cognitive scores but not to any of the individual driving metrics (e.g., CSF Aβ42/Aβ40 ratio).ConclusionsDifferent biomarkers are associated with different aspects of driving and cognitive functioning. These distinct relationships may help in understanding how different biological changes that occur during the preclinical stage of AD impact various sensorimotor and cognitive processes.