PET/MR imaging of LC‐NE function for interrogation of health disparity in preclinical AD

TL;DR

This study uses PET/MRI imaging to show that African Americans have higher but faster-declining brain chemical transporters linked to Alzheimer's disease, suggesting stress may contribute to health disparities.

Contribution

The study demonstrates that LC-NE function is sensitive to both age and stress effects, and validates [11C]MRB-PET as a tool for detecting health disparities in preclinical Alzheimer's.

Findings

African Americans had higher NE transporter availability in youth but faster decline with age.

Older African Americans showed steeper decline in LC transporter availability compared to whites.

Group differences in transporter availability decreased with age due to faster decline in African Americans.

Abstract

Locus Coeruleus (LC) is the earliest location for tauopathy and its decline is highly correlated with AD symptomatology. The LC‐NE system produces functional adaptive changes in response to chronic stress. [11C]MRB‐PET allows in vivo quantification of NE transporter (NET) in humans. Our previous data (ages 25‐55) demonstrated that African Americans (AA) had greater NET availability but with faster decline rate compared to whites (W), suggesting chronic lifetime discrimination/stress may contribute to health disparity. The goal of this study is to use a larger sample size and older cohort (55‐75) to further compare age and race effects on NET.

Subjects underwent a 90‐min dynamic [11C]MRB‐PET via simultaneous PET/MRI. The segmentation of ROIs and LC delineation using TSE‐neuromelanin was established via registration of PET, MRI, and Freesurfer via Firevoxel (https://wp.nyu.edu/Firevoxel), Binding potential (BPND, index of specific binding) using MRTM2 (t*=20 min, k2’=0.022 min‐1) and annual percent change (APC = 100 × (em – 1), m is slope) were calculated.

Participants (38 AA, age: 62.97±4.82; 23 W, age 64.63±5.71) were included in our old cohort. In young cohort, avg BPND values of ROIs (16) from AA (age 34±7) were consistently higher than those from W (Figure 1), while in old cohort, BPND in LC, thalamus, hippocampus, amygdala from AA remains higher, and the group difference was reduced (Figure 2).

In young cohort adults, all ROIs showed larger negative APC in BPND for AA, particularly in AA‐M, e.g., ‐3%/yr in LTH & RAmyg and ‐1%/yr in BS & ROfac; while ‐0.1 & ‐0.12%/yr in BS & ROfac for W. However, in old cohort, only LC and olfactory bulb showed larger negative APC in AA. Figure 3 illustrates that AA had a steeper decline in LC (slope ‐0.026) vs W (‐0.002).

NET availability is higher in young AA and declines faster in old AA. These two competing factors result in a reduced group difference seen in old cohort. We demonstrate that LC‐NE function is sensitive to both age and stress effects and confirm that [11C]MRB‐PET is a promising strategy for early detection of underlying mechanisms for the health disparity in preclinical AD.

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