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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.
Clin Sci (Lond). 2017 Oct 01; 131(19):2451-2468.CS

Abstract

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.

Authors+Show Affiliations

Centre for Neuroregeneration, University of Edinburgh, Edinburgh, U.K.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. Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, 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 karen.horsburgh@ed.ac.uk. Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, U.K.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

28963120

Citation

Duncombe, Jessica, et al. "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." Clinical Science (London, England : 1979), vol. 131, no. 19, 2017, pp. 2451-2468.
Duncombe J, Kitamura A, Hase Y, et al. 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. Clin Sci (Lond). 2017;131(19):2451-2468.
Duncombe, J., Kitamura, A., Hase, Y., Ihara, M., Kalaria, R. N., & Horsburgh, K. (2017). 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. Clinical Science (London, England : 1979), 131(19), 2451-2468. https://doi.org/10.1042/CS20160727
Duncombe J, et al. 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. Clin Sci (Lond). 2017 Oct 1;131(19):2451-2468. PubMed PMID: 28963120.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Duncombe,Jessica, AU - Kitamura,Akihiro, AU - Hase,Yoshiki, AU - Ihara,Masafumi, AU - Kalaria,Raj N, AU - Horsburgh,Karen, Y1 - 2017/09/28/ PY - 2017/05/05/received PY - 2017/08/28/revised PY - 2017/09/04/accepted PY - 2017/10/1/entrez PY - 2017/10/1/pubmed PY - 2017/10/11/medline KW - Alzheimers disease KW - cerebral hypoperfusion KW - cognitive impairment KW - dementia KW - model organisms KW - small vessel disease SP - 2451 EP - 2468 JF - Clinical science (London, England : 1979) JO - Clin Sci (Lond) VL - 131 IS - 19 N2 - 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. SN - 1470-8736 UR - https://www.unboundmedicine.com/medline/citation/28963120/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_ L2 - https://portlandpress.com/clinsci/article-lookup/doi/10.1042/CS20160727 DB - PRIME DP - Unbound Medicine ER -