Interest in how vascular factors contribute to dementia is ascendant, propelled by a number of factors. One is the widespread use of MRI, which is a highly sensitive (if not always specific) test for cerebrovascular lesions. A second is a string of epidemiological reports revealing that Alzheimer's disease shares many of the well established risk factors for cardiovascular and cerebrovascular disease (Skoog & Gustafson, 2003). Recent autopsy studies using cohorts obtained outside of the potentially winnowing influence of the Alzheimer's disease centers have reminded us that vascular lesions are common in patients with dementia (Neuropathology Group of the Medical Research Council Cognitive Function and Ageing Study, 2001). The Nun study report suggesting that infarcts create an additive or greater effect on mental function in concert with AD pathology (Snowdon et al., 1997) received particularly wide exposure and helped revive interest in combined effects of AD and ischemic lesions. Finally, the discovery that polymorphisms of the apoE gene, long of interest in cardiovascular disease, strongly modify the risk of AD suggested the possibility of shared pathophysiological mechanisms between AD and vascular dementia (Panza et al., 2004; Strittmatter & Roses, 1995). The volume Vascular Dementia, edited by Paul, Cohen, Ott and Salloway, is thus a timely resource for those interested in the numerous issues surrounding the role of vascular factors in dementia.

This volume is intended as a summary of the current state of the field and as a tool for those seeking to advance it. It is not particularly oriented to the practicing clinician, and with good reason; clinical guidelines are hard to justify when basic underlying concepts and definitions are controversial, conflicting, and inadequately validated. The depth of the controversy around vascular dementia is on striking display in the first section of the book, which contains chapters by three major figures in the field, namely Gustavo Roman, Vladimir Hachinksi, and Kurt Jellinger. Roman opens with a spirited argument for his view that “cerebrovascular disease is the most important cause of dementia in the elderly.” In sharp contrast, Hachinski, with co-author Merino, presents a thorough critique of current diagnostic criteria for VasD (which, of course, underpin any prevalence data), concluding that “current [diagnostic] criteria [for VasD] are not interchangeable and are neither sensitive nor specific … therefore, they must be invalid.” Hopes of validating any of the clinical criteria in the near term are dealt a further blow by Jellinger. His chapter, a fine, encyclopedic review of cerebrovascular neuropathology, concedes at the outset that “one of the most controversial and incompletely understood issues is the extent to which vascular pathology contributes to dementia.” The absence of any anchoring pathological “gold standard” considerably complicates life for vascular dementia researchers.

The fundamental problems revealed in these opening chapters are relevant to nearly all chapters that follow. Any compilation of clinical findings, any attempt at diagnostic markers, any mechanistic work done on clinically defined groups must grapple with the certainty of diagnostic errors (the extent of which are unquantifiable), and the near certainty that Alzheimer's disease is present to a variable (again, unquantifiable) degree in the living subjects under study. Further complicating the issue is the widely acknowledged heterogeneity of lesions and mechanisms associated with cerebrovascular disease. The extent to which these issues are recognized varies considerably from chapter to chapter, but having them cast so starkly at the outset helps the critical reader approach the remainder of the book.

A distinct strength of this book is the breadth of topics it covers. Vascular Dementia is organized into six sections: an introduction; basic mechanisms; cognitive, psychiatric and functional impacts; neuroimaging; interactions with Alzheimer's disease; and management. Within are chapters covering topics ranging from epidemiology to pathology, from clinical features to molecular biological mechanisms, from diagnosis to the future of pharmacological intervention. The volume is thus of value to a wide range of investigators, and encourages a broad and multi-disciplinary approach to thinking about the topic.

Several chapters are particularly valuable. In addition to Jellinger's neuropathology review there are two reviews of clinical neuropsychological findings (by Jefferson et al. and also Libon et al.), which together cover the relevant literature well. Moser et al.'s review of white matter effects on cognitive function will be a very useful starting point for anyone interested in that topic. In addition, Kumar et al. do a nice job of trying to sort out the psychiatric/behavior disturbance literature while recognizing the limitations of this literature. Salloway and Desbien's chapter includes a very helpful overview of cerebral autosomal dominant arteriopathy with subcortical infarcts and lacunes (CADISIL), a relatively uncommon but potentially scientifically informative form of genetically determined vascular dementia. Gunstead and Browndyke's compilation of the epidemiological data on mixed (vascular and Alzheimer's) dementia, which includes much data on vascular dementia as well and which should prove a useful resource for those who want to tackle the tricky issue of prevalence (as the data there show, the oft repeated claim that vascular dementia is the second leading cause of dementia stands on shaky ground).

Other chapters present either intriguing preliminary data or discussions of potentially promising approaches to unraveling this complex knot. Moss and Jonak present a primate model for studying hypertensive effects on cognition. Mungas gives an illustration of the power of sophisticated statistical modeling to help determine the independent and combined effects of multiple pathological markers simultaneously. And, on the whole, the section reviewing possible biological mechanisms through which vascular factors may promote the pathologic changes of AD presents a wide range of stimulating ideas.

Finally, the topic of treatment is not neglected. Unfortunately, as the review by Erkinjuntti et al. makes clear, there is no well supported pharmacological approach to treating either the symptoms or underlying pathophysiology of this disease (other than, of course, the modification of vascular risk factors). However, the closing chapter by Fisher and Selim does a very nice job of cataloging the numerous promising targets that ischemia presents for intervention, leaving good reason to hope for real progress.

It has become abundantly clear that the aging brain is, more often than not, affected by multiple pathological changes simultaneously. Nothing in this volume seriously challenges the idea that Alzheimer's disease is the major cause of dementia in old age. However, it provides ample data and discussion to stir the thinking of the Alzheimer-centric skeptic as well as that of the committed investigator of vascular dementia. There is much here to suggest that the middle ground that explores the relative contributions and interactions of these two common disease processes may turn out to be most productive.