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Clin Sci (Lond). 2017 Sep 28;131(19):2451-2468. doi: 10.1042/CS20160727. Print 2017 Oct 1.

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.

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Centre for Neuroregeneration, University of Edinburgh, Edinburgh, U.K.
National Cerebral and Cardiovascular Center, Osaka, Japan.
Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.
National Cerebral and Cardiovascular Center, Osaka, Japan


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 β (Aβ) 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.


Alzheimers disease; cerebral hypoperfusion; cognitive impairment; dementia; model organisms; small vessel disease

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