Quantitative R1 in the locus coeruleus in Alzheimer’s disease dementia

Abstract

AbstractBackgroundPrior studies employing neuromelanin‐sensitive MRI have linked neurodegeneration in the locus coeruleus (LC) to Alzheimer’s disease (AD) pathology. MPnRAGE (Keckskemeti et al., 2016), a novel MRI technique developed at UW‐Madison, generates multiple inversion recovery contrasts and quantitative T1 relaxometry. Quantitative R1 (= 1/T1), the longitudinal relaxation rate, is sensitive to brain myelin, lipid, and iron content according to post‐mortem studies. As prior studies suggest altered quantitative R1 (QR1) among individuals with AD pathology, this imaging marker may be sensitive to AD‐associated pathology in the LC, one of the first regions in the brain to show signs of AD pathology (Braak et al., 2011). Here we performed preliminary assessments to test for differences in QR1 among individuals with and without clinical mild cognitive impairment (MCI‐AD), or AD dementia. We hypothesized that R1 would be lower among individuals with AD and MCI compared to unimpaired controls.MethodParticipants were enrolled in the Alzheimer’s Disease Connectome Project (ADCP) at UW‐Madison. 103 older adults diagnosed as cognitively unimpaired (N=53), MCI‐AD, and AD‐Dementia (Table 1) underwent MPnRAGE at a 1mm3 resolution. MPnRAGE‐derived QR1 maps were registered to MNI space using SPM12. LC masks (from Betts et al., 2017) were transformed to subject space to extract mean R1 in the bilateral LC using the Marsbar toolbox. Multiple linear regression was run within Rstudio to investigate the relationships between age, R1, and diagnosis. The main effects of interest included age and diagnosis, as well as their interaction. Sex was included as a covariate.ResultNo significant associations were found between QR1 and age, diagnostic status, and their interaction. The main effect of age on R1 trended toward significance (p=0.059). Age trends are shown in Figure 1. Sex was not a significant covariate.ConclusionWhile QR1 was not significantly associated with age or clinical diagnosis within the LC, further research will evaluate the extent to which QR1 is altered among other regions affected by AD pathology. Further, R1 could be tested between groups stratified by AD biomarker status. Finally, the LC is a small structure, thus future work could also test R1 estimated at higher resolution.