Risk Factors Associated with Cortical Thickness and White Matter Hyperintensities in Dementia Free Okinawan Elderly

Lisa C. Silbert, David Lahna, Nutta On Promjunyakul, Erin Boespflug, Yusuke Ohya, Yasushi Higashiuesato, Junko Nishihira, Yuriko Katsumata, Takashi Tokashiki, Hiroko H. Dodge

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


BACKGROUND: Cortical gray matter (GM) and white matter (WM) deterioration are signals of neurodegeneration and increased dementia risk; however, their specific etiologies in dementia-free aging is unclear. OBJECTIVE: The objective of this study was to examine potentially modifiable risk factors of GM and WM degeneration in a well-characterized cohort of dementia-free elderly. METHODS: 96 Okinawan elderly participants (age 83.6) from the Keys to Optimal Cognitive Aging Project (KOCOA) underwent MRI and cognitive evaluation. Serum markers of inflammation (interleukin-6 (IL-6), high sensitivity C-reactive protein), cerebrovascular disease (systolic blood pressure (SBP) 140+, hemoglobin A1C (HgbA1C), total cholesterol), and essential minerals (copper (Cu), magnesium, and calcium) were examined in relation to mean cortical thickness (MCT) and white matter hyperintensities (WMH), adjusting for age and gender. Voxel-based morphometry (VBM) analyses identified relationships between regional GM density and the above markers. RESULTS: Decreased MCT was associated with SBP 140 + (p = 0.029) and increased serum IL-6 (p = 0.036), HgbA1C (p = 0.002), and Cu (p = 0.025). In VBM analyses, increased IL-6, HgbA1C, and Cu were associated with decreased GM density in temporal lobe regions. HgbA1C (p = 0.004) was associated with greater WMH volume. CONCLUSIONS: Peripheral markers of Cu, CVD risk, and inflammation are associated with MRI-markers of decreased brain health in dementia-free Okinawan elderly, with regional cortical thinning in areas involved in early accumulation of Alzheimer's disease pathology. Results identify potentially modifiable biomarkers as targets in the prevention of dementia in older individuals.

Original languageEnglish
Pages (from-to)365-372
Number of pages8
JournalJournal of Alzheimer's Disease
Issue number1
StatePublished - 2018


  • Aging
  • Alzheimer’s disease
  • atrophy
  • brain
  • cerebrovascular disorders
  • cognitive aging
  • copper
  • inflammation
  • magnetic resonance imaging
  • micronutrients
  • vascular disease

ASJC Scopus subject areas

  • General Neuroscience
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health


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