Alterations in myelin content are related to cognitive performance in nondemented older adults: Findings from the wisconsin registry for Alzheimer’s prevention study

Novel imaging biomarkers that directly target myelin provide unique information about the brain health. While converging studies underscore the relationship between white matter microstructure and cognitive function, particularly in the domain of processing speed, there is still a paucity of information about the relationship between other neurocognitive measures and myelin health. Defining the alterations of myelo-architecture associated with cognitive performance may provide additional information about the mechanisms underlying cognitive changes in healthy and pathological aging. 57 participants from the Wisconsin Registry for Alzheimer's Prevention study (62.84±6.62 years; range 45-74) underwent an extensive neuropsychological battery that was used to generate 4 factor scores: (1) Speed and flexibility, (2) Working memory, (3) Verbal learning and memory, and (4) Immediate memory. The cohort is enriched for Alzheimer's disease (AD) risk factors including parental family history and APOE4 genotype. Three-pool mcDESPOT processing of participants's MRI images was used to calculate T1, T2, and myelin water fraction maps (MWF). Parameter maps were transformed to a population template space using the Advanced Normalization Tools software package. In SPM12, each cognitive factor was regressed on T1, T2, and MWF maps (p<0.001, uncorrected), respectively, after adjustment for age, gender, and time interval between MRI scan and neuropsychological evaluation (1.9±4.1months). In addition to known MWF associations with processing speed and flexibility, we found a positive relationship between working memory and MWF in the genu of the corpus callosum, anterior and middle cingulate gyrus, as well as other regions in the prefrontal cortex that have been shown to play a role in working memory (Figure 1). In contrast, speed and flexibility performance associations localized primarily to posterior cingulate gyrus and precuneus. No significant relationship was found between MWF and immediate memory nor verbal learning and memory.