The growing burden of Alzheimer's disease.

Most dementias in people at least 65 years of age are attributable to Alzheimer's disease (AD). While approximately 5.4 million Americans are now believed to have AD, the AD population is expected to nearly triple over the next 40 years, reaching approximately 14.5 million. Presently, there is no cure for AD, but a 2-year delay in AD onset would reduce the expected prevalence by 1.94 million within 50 years. The most important risk factor for AD is age, followed by presence of the apolipoprotein E-4 allele. Other risk factors for AD include sex (female), history of head trauma, family history of Down syndrome or dementia, and cerebrovascular risk factors. The initial neurodegenerative process that causes AD is unknown. However, it is accepted that the presence of amyloid plaques, neurofibrillary tangles, neuronal loss (and synapses), and cerebral amyloid angiopathy are the central pathogenic events. There is selective vulnerability of the limbic system and heteromodal association areas in AD pathology. The most affected neurotransmitter in AD is acetylcholine, as enzymes that are part of its metabolic pathway are depleted. The clinical presentation of AD is heterogeneous and insidious, and the psychological and financial effects of AD on caregivers and family members are significant.