Published online by Cambridge University Press: 12 October 2009
Down's syndrome (DS) occurs in about 1/800 live births (Adams et al., 1981) and accounts for about 17% of the mentally handicapped population (Heller, 1969). An association between DS and dementia was first noted well over a century ago by Fraser & Mitchell (1876), who wrote ‘in not a few instances, however, death was attributed to nothing more than a general decay – a sort of precipitated senility’. Nevertheless, it was not until much later (Struwe, 1929; Jervis, 1948) that the linkage between this ‘senile decay’ and the occurrence within the brain of the pathological lesions of Alzheimer's disease (AD), namely senile plaques (SP) and neurofibrillary tangles (NFT), was noted. More recently, a number of studies have shown there to be an excess of DS births among the relatives of AD patients, particularly early onset AD families (Heston et al., 1981; Heyman et al., 1983; Broe et al., 1990; Van Duijn et al., 1991). Conversely, there is an increased risk of AD among mothers of DS children (Yatham et al., 1988; Schupf et al., 1994). Such observations support the pathological observations of shared etiopathogenetic causes for AD and DS. Life expectancy for people with DS has progressively risen with nearly half individuals living to beyond 50 years of age (Dupont et al., 1986; Baird & Sadovnick, 1987; Holland & Moss 1997) and with this the problems of ‘precocious ageing’ and dementia in DS have gained prominence.