White matter lesions and brain gray matter volume in cognitively normal elders

Cyrus A. Raji, Oscar L. Lopez, Lewis H. Kuller, Owen T. Carmichael, William T. Longstreth, H. Michael Gach, John Boardman, Charles B. Bernick, Paul M. Thompson, James T. Becker

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


Cerebral white matter lesions (WMLs) reflect small vessel disease, are common in elderly individuals, and are associated with cognitive impairment. We sought to determine the relationships between WMLs, age, gray matter (GM) volume, and cognition in the Cardiovascular Health Study (CHS). From the Cardiovascular Health Study we selected 740 cognitively normal controls with a 1.5 T magnetic resonance imaging (MRI) scan of the brain and a detailed diagnostic evaluation. WML severity was determined using a standardized visual rating system. GM volumes were analyzed using voxel-based morphometry implemented in the Statistical Parametric Mapping software. WMLs were inversely correlated with GM volume, with the greatest volume loss in the frontal cortex. Age-related atrophy was observed in the hippocampus and posterior cingulate cortex. Regression analyses revealed links among age, APOE*4 allele, hypertension, WMLs, GM volume, and digit symbol substitution test scores. Both advancing age and hypertension predict higher WML load, which is itself associated with GM atrophy. Longitudinal data are needed to confirm the temporal sequence of events leading to a decline in cognitive function.

Original languageEnglish
Pages (from-to)834.e7-834.e16
JournalNeurobiology of Aging
Issue number4
StatePublished - Apr 2012


  • Age
  • Cognition
  • Gray matter volume
  • White matter lesions


Dive into the research topics of 'White matter lesions and brain gray matter volume in cognitively normal elders'. Together they form a unique fingerprint.

Cite this