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

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Abstract

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.

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Abbreviations

Aβ:

Amyloid-β

AD:

Alzheimer’s disease

APP:

Amyloid precursor protein

AT1:

Angiotensin II type I

CCAs:

Common carotid arteries

PCAs:

Posterior communicating arteries

ROS:

Reactive oxygen species

VCI:

Vascular cognitive impairment

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Authors and Affiliations

  1. Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria, 3800, Australia

    Hyun Ah Kim, Alyson A. Miller, Grant R. Drummond & Christopher G. Sobey

  2. Department of Medicine, Monash Medical Centre, Southern Clinical School, Monash University, Clayton, Victoria, Australia

    Amanda G. Thrift, Thanh G. Phan & Velandai K. Srikanth

  3. School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland, Australia

    Thiruma V. Arumugam

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  1. Hyun Ah Kim
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  2. Alyson A. Miller
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  3. Grant R. Drummond
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  4. Amanda G. Thrift
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  5. Thiruma V. Arumugam
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  7. Velandai K. Srikanth
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  8. Christopher G. Sobey
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Correspondence to Christopher G. Sobey.

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Kim, H.A., Miller, A.A., Drummond, G.R. et al. Vascular cognitive impairment and Alzheimer’s disease: role of cerebral hypoperfusion and oxidative stress. Naunyn-Schmiedeberg's Arch Pharmacol 385, 953–959 (2012). https://doi.org/10.1007/s00210-012-0790-7

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