Midlife vascular risk factor exposure accelerates structural brain aging and cognitive decline

Neurology. 2011 Aug 2;77(5):461-8. doi: 10.1212/WNL.0b013e318227b227.


Objective: Our aim was to test the association of vascular risk factor exposure in midlife with progression of MRI markers of brain aging and measures of cognitive decline.

Methods: A total of 1,352 participants without dementia from the prospective Framingham Offspring Cohort Study were examined. Multivariable linear and logistic regressions were implemented to study the association of midlife vascular risk factor exposure with longitudinal change in white matter hyperintensity volume (WMHV), total brain volume (TBV), temporal horn volume, logical memory delayed recall, visual reproductions delayed-recall (VR-d), and Trail-Making Test B-A (TrB-A) performance a decade later.

Results: Hypertension in midlife was associated with accelerated WMHV progression (p < 0.001) and worsening executive function (TrB-A score; p = 0.012). Midlife diabetes and smoking were associated with a more rapid increase in temporal horn volume, a surrogate marker of accelerated hippocampal atrophy (p = 0.017 and p = 0.008, respectively). Midlife smoking also predicted a more marked decrease in total brain volume (p = 0.025) and increased risk of extensive change in WMHV (odds ratio = 1.58 [95%confidence interval 1.07-2.33], p = 0.021). Obesity in midlife was associated with an increased risk of being in the top quartile of change in executive function (1.39 [1.02-1.88], p = 0.035) and increasing waist-to-hip ratio was associated with marked decline in TBV (10.81 [1.44-81.01], p = 0.021). Longitudinal changes in brain structure were significantly correlated with decline in memory and executive function.

Conclusions: Midlife hypertension, diabetes, smoking, and obesity were associated with an increased rate of progression of vascular brain injury, global and hippocampal atrophy, and decline in executive function a decade later.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aging*
  • Apolipoproteins E / genetics
  • Brain / pathology*
  • Cerebrovascular Circulation / physiology*
  • Cognition Disorders / pathology*
  • Cohort Studies
  • Female
  • Humans
  • Hypertension / physiopathology
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Regression Analysis
  • Risk Factors
  • Statistics as Topic


  • Apolipoproteins E