BACKGROUND: Disease models are useful for prospective studies of pathology, identification of molecular and cellular mechanisms, pre-clinical testing of interventions, and validation of clinical biomarkers. Here, we review animal models relevant to vascular cognitive impairment (VCI). A synopsis of each model was initially presented by expert practitioners. Synopses were refined by the authors, and subsequently by the scientific committee of a recent conference (International Conference on Vascular Dementia 2015). Only peer-reviewed sources were cited.
METHODS: We included models that mimic VCI-related brain lesions (white matter hypoperfusion injury, focal ischaemia, cerebral amyloid angiopathy) or reproduce VCI risk factors (old age, hypertension, hyperhomocysteinemia, high-salt/high-fat diet) or reproduce genetic causes of VCI (CADASIL-causing Notch3 mutations).
CONCLUSIONS: We concluded that (1) translational models may reflect a VCI-relevant pathological process, while not fully replicating a human disease spectrum; (2) rodent models of VCI are limited by paucity of white matter; and (3) further translational models, and improved cognitive testing instruments, are required.
We are grateful to Professor Amos D Korczyn for his contributions to the VCI
field and for his helpful comments on this review.
AHH gratefully acknowledges funding from Alzheimer’s Drug Discovery
Foundation (ADDF grant no. 20140901), Alzheimer’s Society UK (PG146/151)
and Alzheimer’s Research UK (PPG2014A-8). SMA received research funding from the British Heart Foundation and EPSRC (UK). CC is funded by the
MRC (UK) Centre for Doctoral Training in Regenerative Medicine (grant no.
EP/L014904/1). AMT was supported in this work by Israel Science Foundation
(ISF) Grant 1353/11.
- Dementia, Vascular/genetics
- Disease Models, Animal
- Risk Factors