Correlates of neuroimaging biomarkers in a middle‐age racially diverse cohort: Updates from the association between cardiovascular risk and preclinical Alzheimer’s Disease pathology (ASCEND) study

Abstract Background Black individuals (BIs) are at an increased risk of Alzheimer’s disease (AD) than white individuals (WIs), which is partially explained by increased prevalence of vascular risk, in conjunction with structural inequities including healthcare. Studies suggest that neuroimaging and CSF AD biomarkers may differ across race. We previously identified disparate relationships between brain activity within the frontal and parietal lobes and CSF AD biomarkers. We include analysis of structural and functional neuroimaging in a racially diverse, middle‐aged cohort with an AD family history. We aimed to identify relevant neuroimaging correlates of vascular health and AD, and how relationships may vary according to race. Methods We analyzed data from 76 individuals (29 BIs, 47 WIs). Neuroimaging measures included functional connectivity from functional resting state magnetic resonance imaging (rs‐fMRI) between fronto‐striatal regions (putamen, middle frontal gyrus, superior frontal gyrus), regions of the default mode network (hippocampus, parrahippocampal gyrus (PHG), ventromedial prefrontal cortex, inferior parietal lobule, temporal pole), structural neuroimaging (hippocampal volumes), and regional white matter hyperintensity volumes (frontal, temporal, parietal, occipital, cerebellar volumes). AD biomarkers included CSF phospho‐tau, total tau, & AB42. We included a race X CSF biomarker interaction term in our linear models. Results We identified a race X tau and race X AB42 interaction term for connectivity measures between the middle frontal and superior frontal gyri and the putamen such that as biomarker burden increased, connectivity between these regions decreased within BIs. PHG to temporal pole connectivity also exhibited these same relationships to CSF tau and AB42. Hippocampal volumes did not exhibit relationships to AD biomarkers. We identified a significant race X CSF Ab42 interaction term such that increased AD CSF biomarker burden was related to increased WMH volume in the temporal and parietal lobe. Conclusion We extend previous work in rs‐fMRI of AD to a middle‐aged cohort, supporting neuroimaging and CSF biomarker relationships may differ by race. Front‐striatal connectivity may be a clinically relevant biomarker in mid‐life studies of AD, sensitive to CSF AD biomarker levels. Results support previous consensus that functional and WM measures are more sensitive to early AD pathology and extends this knowledge to BIs.