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IC‐P‐104: LONGITUDINAL CHANGES OF STRUCTURAL AND FUNCTIONAL CONNECTIVITY AND CORRELATIONS WITH GENETICS AND NEUROCOGNITIVE METRICS
Author(s) -
Zhou Yongxia,
Zhou Patrick,
Leon Mony J.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.4218
Subject(s) - neurocognitive , diffusion mri , neuroimaging , psychology , correlation , neuroscience , medicine , cognition , magnetic resonance imaging , mathematics , radiology , geometry
Background: Sparsely myelinated brain regions develop tangle pathology in Alzheimer’s disease (AD; Braak & Tredici, 2015) and high CSF phosphorylated tau (p-tau) is associated with lower myelin content as shown by cross-sectional neuroimaging (Dean et al, 2017). Here, we tested whether baseline CSF p-tau is associated with longitudinal change in myelin content, and secondarily if changes in myelin associate with cognitive performance over time. Methods: 42 participants from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) underwent one lumbar puncture, longitudinal mcDESPOT MRI, and longitudinal neuropsychological testing. All participants were cognitively unimpaired (MMSE: median1⁄430, range1⁄428-30). Mixed models were used for both analyses. Outcome variables were either myelin content, assessed with the mcDESPOT-derived myelin water fraction (MWF), or cognition. MWF was extracted from white matter regions: uncinate, inferior and superior longitudinal fasciculi, inferior-frontal orbital fasciculus, cingulum, and forceps major and minor. A modified Preclinical Alzheimer’s Cognitive Composite (PACC) was used as the cognitive outcome. A primary model with mean MWF as the outcome included random intercepts and slopes nested within subjects and fixed effects of CSF p-tau, age, and sex. A secondary model with PACC as the outcome included random intercepts and age-related slopes for each subject as well as timevarying mean MWF, and fixed effects of age, sex, education, and CSF p-tau. All models were fitted using SPSS and considered significant at unadjusted p<.05.Results: Participants in this sample reflected the larger WRAP cohort: middle-aged (LP age 1⁄4 60.49 6 6.21), 71.4% female, and 69% had a parental history of AD. CSF p-tau was associated with MWF across several bilateral white matter tracts (Table). Change in PACC (b1⁄4-2.21, p1⁄4.047) was associated with MWF change in left cingulum projecting to cingulate gyrus; no effects in other tracts reached significance. Conclusions: Across several tracts, higher p-tau was associated with MWF decreases, suggesting that myelin degeneration and development of tangle pathology are longitudinally associated. A positive longitudinal slope on PACC was associated with decreasing MWF, although the significant effect was limited to left cingulum. Additional studies are needed to elucidate the relationship between myelin degeneration, accruing pathology, and cognitive function.