The effect of white matter hyperintensities on neurodegeneration in mild cognitive impairment

Giuseppe Tosto, Molly E. Zimmerman, Jamie L. Hamilton, Owen T. Carmichael, Adam M. Brickman

Research output: Contribution to journalArticlepeer-review

56 Scopus citations


Introduction It is unclear whether white matter hyperintensities (WMHs), magnetic resonance imaging markers of small-vessel cerebrovascular disease, promote neurodegeneration and associated clinical decline in Alzheimer's disease (AD), or simply co-occur with recognized pathogenic processes. Methods In 169 patients with mild cognitive impairment, followed for 3 years, we examined the association of (1) baseline regional WMH and cerebral spinal fluid-derived t-tau (total tau) with entorhinal cortex atrophy rates, as a marker of AD-related neurodegeneration, and conversion to AD; and (2) baseline regional WMH with change in t-tau level. Results In participants with low baseline t-tau, higher regional WMH volumes were associated with faster entorhinal cortex atrophy. Higher parietal WMH volume predicted conversion to AD in those with high t-tau. Higher parietal and occipital WMH volumes predicted increasing t-tau. Discussion WMHs affect AD clinical and pathologic processes both directly and interacting with tau.

Original languageEnglish (US)
Pages (from-to)1510-1519
Number of pages10
JournalAlzheimer's and Dementia
Issue number12
StatePublished - Dec 1 2015
Externally publishedYes


  • Alzheimer's disease
  • CSF tau
  • Mild cognitive impairment
  • White matter hyperintensities

ASJC Scopus subject areas

  • Clinical Neurology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Epidemiology
  • Health Policy


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