Over the course of the last hundred years our understanding of dementia has undergone considerable change. For much of that time ‘senility’ was seen as an almost inevitable concomitant of ageing and was usually attributed to atherosclerosis. In the post-war period, a concept of multi-infarct dementia emerged, but at the same time Alzheimer’s disease (AD) came to be seen not as a rare young-onset disorder but as the cause of most cases of dementia. Indeed, the concept of dementia itself was built around the impairments seen in AD, notably the impairment of memory. With greater understanding of dementia, particularly its pathological basis, it came to be realized that many different kinds of pathology can produce a dementia syndrome and that multiple types of pathology are the rule rather than the exception. This chapter aims to review our current understanding of how cerebrovascular disease contributes to cognitive impairment in order to assist those involved in the assessment and management of people with cognitive impairments to understand the strengths and limitations of our current concepts, and to inform diagnosis and management.

In this chapter we summarize the more important structures in the brain with which it is essential to be familiar when studying the pathological basis of dementia. As described in Chapter 3 many dementing conditions are impossible to distinguish on naked eye examination of the brain since they do not display gross regional pathology. In order to reach the correct diagnosis, it is necessary to select the appropriate areas for more detailed examination. To do that requires knowledge of the parts of the brain that are significant in the particular context of dementia. For more detailed information textbooks of neuroanatomy such as Paxinos (1990), Heimer (1995), Parent (1996), or Nolte (2001) should be consulted.

Cerebral cortex

Chapter 1 has already emphasized the crucial importance of the cerebral cortex for the cognitive functions which deteriorate in dementia. The cerebral cortex can be divided anatomically into a phylogenetically older and simpler allocortex consisting of the hippocampus and closely related entorhinal cortex, subiculum and olfactory regions, and the remaining, much more voluminous and phylogenetically more recent, neocortex.

Hippocampus, subiculum and entorhinal cortex (archicortex allocortex)

These structures have already been mentioned in Chapter 1 but because of their importance it is worth providing a brief supplementary account here. Excellent reviews of the structure of the human hippocampus and related cortex can be found in Amaral and Insausti (1990) and Duvernoy (1988).

The entorhinal cortex lies in the uncus and anterior parahippocampal gyrus and forms an intermediate type of cortex between the complex six-layered neocortex of the temporal lobe and the simpler, basically three-layered, cortex of the hippocampus.

The first edition of this book was conceived with the intention of providing a practical guide to the neuropathological diagnosis of dementia. It was intended particularly for those who did not regard themselves as experts in this increasingly complex field. The relatively small number of authors was encouraged to share their diagnostic experience with others. This second edition still aims to provide practical assistance in this way, but it now goes further than that. The pace of scientific research advances in this field of dementia is such that it has become a formidable enough task for an expert to remain fully conversant with his or her own subfield, let alone with the field as a whole. Therefore we have aimed to widen the authorship greatly so that many chapters could be written by those specialists with research interests in the topic that is covered by each. We are delighted that those approached have responded so generously and enthusiastically since the outstanding contributions from the authors have made the second edition the most up-to-date and comprehensive monograph on the neuropathology of dementia. Because of the wider international authorship it has also been possible to extend the scope of the coverage of each topic to include more about research findings and the background science so that the book can now claim to provide comprehensive coverage of current understanding of the dementias rather than a more restricted practical guide. We hope, therefore, that a wider readership of neurobiologists and clinicians as well as pathologists will find much of interest here. Those familiar with the first edition will find that there are many new chapters and even more new authors contributing to the second edition.

In this chapter we consider a number of diverse pathological conditions that may occasionally give rise to a clinical picture in which dementia predominates (Table 23.1). Other neurological features are also likely to be present at some stage in the course of these diseases. In some, perhaps most, such cases these other clinical features may have led to the correct diagnosis being established before clinical dementia develops, but in a few the diagnosis may be impossible to achieve before death. Therefore, a pathologist can expect to encounter these diseases occasionally among cases of dementia presenting at autopsy. Full treatment of pathological aspects of these diseases and their illustration is beyond the scope of this chapter and for details a more general textbook of neuropathology should be consulted, e.g. Greenfield's Neuropathology (Graham & Lantos, 2002) or Davis and Robertson's Textbook of Neuropathology (1996).

Neurodegenerative conditions

Neuronal intranuclear hyaline inclusion disease (NIHID)

Neuronal intranuclear hyaline inclusion disease (NIHID) is a rare neurodegenerative disorder characterized by the presence of large eosinophilic inclusions in neuronal nuclei in a wide distribution (Sung et al., 1980; Funata et al., 1990). Whilst most cases present clinically with predominantly motor or other non-cognitive problems, some cases have had dementia (Weidenheim & Dickson, 1995). The neuronal inclusions are present in peripheral ganglionic neurons as well as at all levels of the CNS from cerebral cortex to spinal cord. In addition to the presence of neuronal inclusions, there may be somewhat smaller inclusions in astrocytic nuclei. Neuronal inclusions consist ultrastructurally of haphazardly arranged 10 nm diameter straight filaments without any surrounding membrane.

Introduction

The ancient term hydrocephalus refers to an excessive accumulation of fluid (water) inside the head. It is most readily detected in infants and children with congenital hydrocephalus since its existence before the skull sutures are closed causes the formation of an enlarged head. Such children have long been recognized commonly to have mental impairment, manifest as mental retardation, although the extent of this is very variable. Morgagni (1769) first described hydrocephalus due to enlarged cerebral ventricles in an adult without head enlargement. If this condition develops insidiously during adult life, dementia is an almost invariable accompaniment, though not the only one. More familiarly hydrocephalus in adults develops acutely or subacutely and presents with symptoms of raised intracranial pressure – headache, vomiting and drowsiness. However, in this chapter we are concerned with chronic hydrocephalus in adults, a condition in which symptoms and signs of raised intracranial pressure are commonly clinically absent and in which the cerebrospinal fluid (CSF) pressure is often normal when measured randomly – hence the commonly used term – normal pressure hydrocephalus (NPH). The recognition of this condition, and the realization that it is responsible for some cases of progressive dementia in adults are recent (Riddoch, 1936; Foltz & Ward 1956; McHugh, 1964; Hakim & Adams, 1965; Adams et al., 1965). Cases of NPH, some of which respond well to a shunting procedure, are to be distinguished from cases of dementia due to neurodegenerative diseases in which the ventricles dilate as a consequence of cerebral atrophy (hydrocephalus ex vacuo).

The post-mortem examination in cases of dementia

It has been said, with a good deal of truth, that the answer to every question in medicine is in three parts: first, take a history, second, make a physical examination, and third, perform the relevant special tests and investigations. For the pathologist, the first two parts of this rubric are fulfilled by reading the patient's chart. The third is the performance of what, in at least one sense, is the ultimate diagnostic test, the post-mortem examination.

History and examination

The clinical information available to the pathologist called upon to perform an autopsy examination on a case of dementia is extraordinarily variable. At one extreme is the patient who has been studied over an extended period where the quality and extent of cognitive failure has been documented and, often, a presumptive pathological diagnosis is made. This type of history is often supplemented by more or less objective tests of intellectual function and the results of numerous investigations. Patients submitted to this degree of investigative rigour are often in centres that have a particular interest or active research programme into dementia. In these circumstances it can (we hope) be assumed that there is good liaison between the clinical service and the pathology department and the cases will be dealt with according to protocol.

The opposite end of this particular spectrum is the patient coming to autopsy examination who is reported to have an unspecified degree of cognitive decline, variously described in imprecise terms. In such cases recourse to considerable ingenuity is required to form an idea of the nature and severity of the decline. Clues can sometimes be gleaned from the nursing notes or even from the patient's address.