Luigi Amaducci memorial award winner's paper 2003. A neurologist's view of Alzheimer's disease and dementia.
Senile dementia was the third most common admission diagnosis for New York psychiatric hospitals at the start of the twentieth century and the distinction between vascular and senile dementia was understood by psychiatrists even then. The term Alzheimer's disease (AD) was originally introduced to distinguish a pre-senile dementia from the common general paresis, but Alzheimer raised the possibility that pre-senile AD might not be distinguishable in clinical or histological terms from senile dementia. By the late 1970s it had become clear that the most common disorder producing dementia in elderly people was clinically and pathologically identical to pre-senile AD. AD is malignant, reducing remaining life expectancy by almost half and raising the risk of death over five years threefold (cancer raises it fourfold). Synapse loss associated with beta amyloid oligomers is a strong determinant of cognitive decline in patients with AD. Tau-containing neurofibrillary tangles usefully track disease severity. Unmodifiable risk factors include mutations in three genes which affect the production or metabolism of beta amyloid, the risk factor gene for Apolipoprotein [see symol in text]4 and female gender. The overriding risk factor is age, the prevalence of AD doubling with every five years of age until 90. Low education, head injury and low folate levels are examples of potentially modifiable risk factors. Since a delay of onset of five years would halve the number of patients with the disease, clinical trials for such putative protective factors as estrogens, folic acid, vitamin E, statins, and NSAIDs have begun. Cognitive and leisure activity may be protective against the development of AD but any protective function can only be confirmed by clinical trials.
Katzman
Robert
R
Alzheimer Disease Research Center, University of California, San Diego School of Medicine, La Jolla, 92093-0949, USA. rkatzman@ucsd.edu
D000368:Aged; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000209:etiology / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001363:Awards and Prizes; D003704:Dementia / Q000175:diagnosis / Q000209:etiology; D004522:Educational Status; D020022:Genetic Predisposition to Disease; D006801:Humans; D016874:Neurofibrillary Tangles / Q000378:metabolism; D009462:Neurology; D012307:Risk Factors; D012737:Sex Factors
D016229:Amyloid beta-Peptides