Naunyn-Schmiedeberg's Archives of Pharmacology

, Volume 385, Issue 10, pp 953–959 | Cite as

Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress

  • Hyun Ah Kim
  • Alyson A. Miller
  • Grant R. Drummond
  • Amanda G. Thrift
  • Thiruma V. Arumugam
  • Thanh G. Phan
  • Velandai K. Srikanth
  • Christopher G. Sobey


Cerebrovascular disease may lead to a wide range of cognitive changes, referred to collectively as vascular cognitive impairment. Stroke increases the risk of cognitive impairment and dementia, and may contribute to the progression of Alzheimer’s disease (AD). Apart from clinical stroke itself, vascular risk factors are associated with the development of cognitive impairment and dementia. Animal models involving a temporary or permanent interruption of blood flow in the common carotid arteries develop nonprogressive cognitive impairment. Oxidative stress during cerebral hypoperfusion in animal models plays a key role in neuronal death and may thus contribute to the development of cognitive impairment in cerebrovascular disease. Genetic and pharmacological interventions to inhibit the major source of reactive oxygen species, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, are neuroprotective in experimental cerebral ischemia. Recent studies have demonstrated that inhibition of NADPH oxidase activity can mitigate cognitive impairment in rodent models of cerebral hypoperfusion. In this article, we review the evidence linking cognitive impairment and/or AD with NADPH oxidase-dependent oxidative stress, including the renin–angiotensin system.


Cerebral hypoperfusion Vascular cognitive impairment Alzheimer’s disease NADPH oxidase Reactive oxygen species 




Alzheimer’s disease


Amyloid precursor protein


Angiotensin II type I


Common carotid arteries


Posterior communicating arteries


Reactive oxygen species


Vascular cognitive impairment


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Hyun Ah Kim
    • 1
  • Alyson A. Miller
    • 1
  • Grant R. Drummond
    • 1
  • Amanda G. Thrift
    • 2
  • Thiruma V. Arumugam
    • 3
  • Thanh G. Phan
    • 2
  • Velandai K. Srikanth
    • 2
  • Christopher G. Sobey
    • 1
  1. 1.Department of PharmacologyMonash UniversityClaytonAustralia
  2. 2.Department of Medicine, Monash Medical Centre, Southern Clinical SchoolMonash UniversityClaytonAustralia
  3. 3.School of Biomedical SciencesThe University of QueenslandSt LuciaAustralia

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