Impaired Cerebral Hemodynamics and Cognitive Performance in Patients with Atherothrombotic Disease

J Alzheimers Dis. 2015;46(1):137-44. doi: 10.3233/JAD-150052.


Background and objective: Patients with pre-existing atherothrombotic disease are prone to cognitive impairment. We tested whether impaired cerebrovascular reactivity (CVR), a marker of cerebral microvascular hemodynamic dysfunction, is associated with poorer cognitive scores among patients with and without carotid large-vessel disease.

Methods: A subgroup of non-demented patients with chronic coronary heart disease followed-up for 15 ± 3 years was assessed for cognitive function (Neurotrax Computerized Cognitive Battery; scaled to an IQ style scale with a mean of 100 and SD of 15) and for CVR using the breath-holding index (BHI) with transcranial Doppler and for carotid plaques using ultrasound. We assessed cognitive scores in specific domains in patients with and without impaired CVR (BHI <0.47; bottom quartile).

Results: Among 415 patients (mean age 71.7 ± 6.2 y) median BHI was 0.73 (25% 0.47, 75% 1.04). Impaired CVR was associated with diabetes and peripheral artery disease. Adjusting for potential confounders, impaired CVR was associated with lower executive function (p = 0.02) and global cognitive scores (p = 0.04). There was an interaction with carotid large-vessel disease for executive function (p < 0.001), memory (p = 0.03), and global cognitive scores (p = 0.02). In the carotid large-vessel disease group there were pronounced differences by CVR status in executive function (p < 0.001), memory (p = 0.02), attention (p < 0.001), and global cognitive scores (p = 0.001).

Conclusion: Impaired CVR, a marker of cerebral microvascular dysfunction, is associated with poorer cognitive functions and in particular executive dysfunction among non-demented patients with concomitant carotid large-vessel disease. These findings emphasize the importance of cerebral hemodynamics in cognitive performance.

Keywords: Cerebrovascular disorders; dementia; hemodynamics; transcranial Doppler sonography; vascular dementia.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Bezafibrate / pharmacology
  • Bezafibrate / therapeutic use
  • Blood Pressure / drug effects
  • Cerebrovascular Circulation / drug effects
  • Cerebrovascular Disorders / complications*
  • Cerebrovascular Disorders / drug therapy
  • Cognition Disorders / etiology*
  • Female
  • Humans
  • Hypolipidemic Agents / pharmacology
  • Hypolipidemic Agents / therapeutic use
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Neurovascular Coupling / physiology*
  • Ultrasonography


  • Hypolipidemic Agents
  • Bezafibrate