AbstractBackgroundPost‐mortem observations of Alzheimer’s disease (AD) brain suggest that developmental patterns of myelin and AD pathology are inversely related (Braak and Braak, 1996). Myelin injury and repair processes have also been implicated in the amyloid cascade hypothesis (Bartzokis, 2004; Depp et al., 2021). While diffusion‐weighted imaging has been widely applied to examine white matter abnormalities in AD, there remains a dearth of high resolution and high contrast imaging methods that allow for accurate and precise measurement of brain myelin in vivo. Here, we leveraged a novel imaging sequence—MPnRAGE (Kecskemeti et al., 2016; 2018)—to derive R1 maps, a myelin sensitive metric, and assessed the potential of R1 to identify myelin abnormalities in relation to cognitive impairment in AD.Method791 cognitively unimpaired older adults, 30 with dementia, and 43 with MCI enrolled in the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center clinical core study underwent T1‐weighted (T1w) MPnRAGE with motion‐correction. T1w images and R1 maps were reconstructed at 1mm isotropic resolution. Preprocessing steps are outlined in Figure 1. As the T1w image and R1 map are inherently coregistered, no additional preprocessing was applied to the R1 map.ResultA whole‐brain vertex‐wise cortical R1 map for a single participant and bilaterally averaged group mean parcellations for both cortical and WM R1 can be seen in Figure 2. Notably, densely‐myelinated regions are typically spared in AD, while thinly‐myelinated regions are vulnerable to AD pathology. In the cortex, sensory/motor regions exhibited the highest R1 (indicative of greater myelin content) and frontal/temporal regions had the lowest R1. In shallow WM, pericingulate WM exhibited the highest R1 and visual‐adjacent WM had the lowest R1. Participants with dementia and MCI had substantially reduced cortical adjacent WM R1 compared to unimpaired individuals (Figure 3).ConclusionThis is the largest study to date to examine R1 maps among older adults with and without AD. These R1 maps are expected to facilitate analyses between myelin content and regional AD pathology accumulation as indexed by tau and amyloid PET, as well as testing the role of longitudinal myelin injury and repair in disease progression.