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Abstract
IT IS NOW UNDERSTOOD THAT GENETIC FACTORS play a crucial role in the risk of developing Alzheimer's disease (AD). Rare mutations in at least 3 genes are responsible for early-onset familial AD. A common polymorphism in the apolipoprotein E gene is the major determinant of risk in families with late-onset AD, as well as in the general population. Advanced age, however, remains the major established risk factor for AD, although environmental variables may also have some role in disease expression. Some pathogenic factors directly associated with aging include oxidative damage and mutations in messenger RNA. Other factors unrelated to the aging process may, in the future, be amenable to therapeutic intervention by way of estrogen replacement therapy for postmenopausal women, anti-inflammatory drug therapy and reducing Vascular risk factors. Older theories, such as aluminum playing a role in the pathogenesis of AD, have been mostly discarded as our understanding of pathogenic mechanisms of AD has advanced.
Physicians communicating the diagnosis of Alzheimer's disease (AD) to a patient's family are often confronted with the questions: What caused it? Could it have been anything I did? General practitioners and specialists caring for elderly patients are more interested in understanding the etiopathogenesis of this disorder now that there are approved treatments for some of the symptoms of AD and strategies for disease modification and there exists the potential for prevention in the future.` Several factors have contributed to the increased interest in and awareness of the burden AD places on society, expressed by both the medical community and general public4,' The first relates to demographics; the prevalence of AD is the highest in people 85 years of age and older (approximately 26% ),4 and this is the fastest growing segment of the population. In addition, the vague concept of senility has been replaced with specific causes and phenotypes of dementia that can now be accurately identified.
Our understanding of AD has developed in 3 stages. Although the 1907 description by Alois Alzheimer clearly identified the salient clinical and pathological features of the condition,' it was not until the seminal work of Blessed and colleagues' that the disease was recognized, not as a rare neurological disorder, but as the most common cause of dementia. The discovery of...