Evaluation of locus coeruleus changes during aging by post‐mortem brain MRI contrast

Abstract

AbstractBackgroundNeuropathological studies have pointed to the importance of neurodegeneration in the locus coeruleus (LC) as a possible early biomarker of Alzheimer’s Disease (AD). The aim of this study is to explore a non‐invasive MRI technique to evaluate normal and pathological changes in the LC during aging.MethodsSubjects were recruited from our Capital’s Death Verification Service. After obtaining written consent from family members, 24 individuals (55‐94 yrs) were submitted for post‐mortem brain in situ MRI with a 7T scanner. Post‐mortem interval ranged from 7 to 20 hours and body temperature varied from 14.8°C to 26°C. MRI protocol included acquisition of multi‐echo gradient‐echo axial images with 2 mm thickness and 0.4 mm in‐plane resolution. LC signal intensity was evaluated from a single gradient‐echo image presenting the brightest signal for the LC. In the same slice normalized values for the left and right LC were quantified (LNV and RNV) by selecting a ROI on the brightest spot of the LC (one‐pixel sized) and dividing it by the signal intensity measured in the left and right pons, respectively (ROI of approx. 50mm2) (Figure1). Subject’s Clinical Dementia Rating (CDR) was obtained by interviewing a close family member. A two‐tailed paired t‐test was performed between the RNV and the LNV, and dependence with age was analyzed by Pearson correlation.ResultsCDR was 0 (n = 17); 0,5 (n = 2); 1 (n = 1), 2 (n = 1), and 3 (n = 3). LNV was higher than RNV (t(23) = 3.9; p< 0.001 (Figure2). The mean of LNV and RNV (MNV) was higher in individuals with CDR = 0 than in subjects with CDR >0, but subjects with CDR>0 were also significantly elder, and there was a significant effect of age on the MNV (r = ‐ 0,49, p = 0,015), Figure 3.ConclusionMRI LC contrast was able to depict LC changes as a function of age, whereby subjects with symptons seemed to present lower LC intensity. The left LC was consistently brighter than the right LC endorsing results observed in other studies (Betts et al.2019 https://doi.org/10.1016/j.dadm.2019.02.001). Future histopathological analysis will help to elucidate the origin for this signal difference.