title: Vascular cognitive impairment and Alzheimer's disease: role of cerebral hypoperfusion and oxidative stress.
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.
authors.affiliation: Department of Pharmacology, Monash University, Wellington Road, Clayton, Victoria, 3800, Australia.
authors.forename: Hyun Ah
authors.initials: HA
authors.lastname: Kim
authors.forename: Alyson A
authors.initials: AA
authors.lastname: Miller
authors.forename: Grant R
authors.initials: GR
authors.lastname: Drummond
authors.forename: Amanda G
authors.initials: AG
authors.lastname: Thrift
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
authors.forename: Thanh G
authors.initials: TG
authors.lastname: Phan
authors.forename: Velandai K
authors.initials: VK
authors.lastname: Srikanth
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Sobey
mesh_terms: D000544:Alzheimer Disease / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control; D004195:Disease Models, Animal; D006801:Humans; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases