Higher cortical myelin is associated with worse performance on cognitive tests: Findings from the Alzheimer’s Disease Connectome Project

Background Brain myelin is known to play an important role in maintaining optimal neuronal function, with deficits in myelin leading to worse performance on cognitive tests. The extent to which cortex‐specific myelin is associated with other cognitive domains, or is impacted by disease processes such as Alzheimer’s disease (AD), is unknown. Here we leverage MPnRAGE‐derived quantitative R1 (Kecskemeti et al., 2016; 2018), a metric sensitive to brain myelin, to assess the role of intracortical myelin in performance on tests of executive function (exec_func), working memory (working_mem), and processing speed (process_speed) in older adults who ranged from cognitively unimpaired to those with dementia. Method 143 older adults (N=75 cognitively unimpaired, N=44 mild cognitive impairment, N=24 dementia) enrolled in the Alzheimer’s Disease Connectome Project underwent T1‐weighted (T1w) MPnRAGE MRI with motion‐correction and testing via the NIH Toolbox Cognitive Battery. Inherently registered quantitative R1 maps and T1w images were reconstructed at 1mm isotropic resolution. The image processing pipeline and composite regions of interest (ROIs) used for analysis can be viewed in Figure 1. Uncorrected standard scores were computed by the NIH Toolbox for each measure of exec_func (dimensional change card sort), working_mem (list sorting), and process_speed (pattern comparison). Multiple linear regression models were employed in R with test scores as the dependent variable, regional R1 as the predictor of interest, and age, sex, and education as covariates. Result Higher R1 was associated with worse exec_func in regions that are affected in AD, including posterior cingulate (ß = ‐62.47, t(1,138) = ‐2.42, p = 0.017) and temporal cortices(ß = ‐123.05, t(1,138) = ‐2.77, p = 0.0064) ROIs. Additionally, higher R1 in temporal cortices was associated with worse working_mem (ß = ‐158.16, t(1,133) = ‐2.84, p = 0.0053) (Figure 2). There were no significant associations between process_speed and regional cortical R1. Conclusion Unexpectedly, higher regional cortical myelin (as indexed by R1) was associated with worse exec_func and working_mem, suggesting higher R1 may be indicative of a regional pathologic process. Future work will test the interactive relationships between amyloid and/or tau pathology and cortical myelin on cognitive performance.