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Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia

Lookup NU author(s): Dr Yoshiki HaseORCiD, Dr Masafumi Ihara, Professor Raj KalariaORCiD


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Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia. While there is considerable overlap between features of vascular cognitive impairment and dementia (VCID) and Alzheimer’s disease (AD), it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia. Sustained cerebral hypoperfusion is suggested to be the cause of white matter attenuation, a key feature common to both AD and dementia associated with cerebral small vessel disease (SVD). White matter changes increase the risk for stroke, dementia and disability. A major gap has been the lack of mechanistic insights into the evolution and progress of VCID. However, this gap is closing with the recent refinement of rodent models which replicate chronic cerebral hypoperfusion. In this review, we discuss the relevance and advantages of these models in elucidating the pathogenesis of VCID and explore the interplay between hypoperfusion and the deposition of amyloid ß (Aß) protein, as it relates to AD. We use examples of our recent investigations to illustrate the utility of the model in preclinical testing of candidate drugs and lifestyle factors. We propose that the use of such models is necessary for tackling the urgently needed translational gap from preclinical models to clinical treatments.

Publication metadata

Author(s): Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria RN, Horsburgh K

Publication type: Review

Publication status: Published

Journal: Clinical Science

Year: 2017

Volume: 131

Issue: 19

Pages: 2451-2468

Print publication date: 28/09/2017

Online publication date: 28/09/2017

Acceptance date: 04/09/2017

ISSN (print): 0143-5221

ISSN (electronic): 1470-8736


DOI: 10.1042/CS20160727

PubMed id: 28963120