Introduction

Due to the increasing longevity of the population across the world, a consistently high prevalence of age-related cognitive deficits has been reported in recent years. Numerous studies have shown that a variety of deficits can be observed clinically, ranging from absence of symptoms with preservation of cognitive and intellectual functions, to severe cognitive disturbances typical of dementia of the Alzheimer type. Alongside the ageing process, several morphological and pathological alterations have been described neuropathologically. The occurrence of the typical Alzheimer-like lesions, namely neurofibrillary tangles (NFT) and senile plaques (SP), is the most obvious feature revealed by microscopic examination in the brain of elderly individuals (Fig. 7.1). However, the extent and distribution of these lesions differ from the classical pathological pattern seen in Alzheimer's disease (AD). Fine morphological techniques have been used to demonstrate that neuronal and synaptic loss also occur during the normal ageing process of the brain. Moreover, changes affecting the cerebral vasculature are not classically described, although they may be an important factor contributing to the age-related deficit in brain function. Finally, subtle alterations in myelinated fibres can be detected in the brains of elderly individuals by using the most advanced in vivo imaging techniques.

NFT and SP distribution in normal ageing

NFT and SP are the two main neuropathological hallmarks required to ascertain the definitive diagnosis of AD (Mirra et al., 1993). However, several studies have shown that a substantial number of these AD-related changes are found in aged individuals with normal cognitive function, demonstrating that the pathological process must begin at an earlier stage when clinical detection is not yet possible (Table 7.1).