Published Online
on December 8, 2005

A more recent version of this article appeared on January 1, 2006

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Submitted on May 11, 2005
Revised on September 2, 2005
Accepted on September 27, 2005

Genetics of Vascular Cognitive Impairment. The Opportunity and the Challenges

Gabrielle G. Leblanc PhD^*; James F. Meschia MD; Donald T. Stuss PhD; and Vladimir Hachinski MD

From the Neurogenetics Group, National Institute of Neurological Disorders and Stroke (G.G.L.), Bethesda, Md; Department of Neurology (J.F.M.), Mayo Clinic, Jacksonville, Fla; Baycrest Centre for Geriatric Care (D.T.S.), The Rotman Research Institute, University of Toronto, Ontario, Canada; London Health Sciences Center (V.H.), University of Western Ontario, London, Ontario, Canada.

^* To whom correspondence should be addressed. E-mail: leblancg{at}ninds.nih.gov.

Background and Purpose--This review considers the current state of knowledge of genetic factors underlying vascular cognitive impairment (VCI).

Summary of Review--We argue here that genes conferring susceptibility to VCI must be of 2 nonmutually exclusive classes: (1) genes that confer susceptibility to cerebrovascular disease, and (2) genes that determine brain tissue responses to cerebrovascular disease (ie, render parenchymal tissue more or less susceptible to injury or able to repair itself after injury). Although some progress has been made in identifying genes of the first class, little has been done to explore genes of the second class. Evidence for the existence of such genes is presented. We discuss the advantages and disadvantages of different forms of cerebrovascular disease for studying these genes, and different study designs that might be used.

Conclusion--The most critical challenge for genetic studies of VCI is to identify quantifiable phenotypes that can be reliably and effectively determined in large samples of subjects.

Key words: cerebrovascular disorders • cognition • dementia • ischemia

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