Alzheimer's Disease Causes, Stages, and Symptoms (cont.)
Howard Crystal, MD
William C. Shiel Jr., MD, FACP, FACR
William C. Shiel Jr., MD, FACP, FACR
Dr. Shiel received a Bachelor of Science degree with honors from the University of Notre Dame. There he was involved in research in radiation biology and received the Huisking Scholarship. After graduating from St. Louis University School of Medicine, he completed his Internal Medicine residency and Rheumatology fellowship at the University of California, Irvine. He is board-certified in Internal Medicine and Rheumatology.
In this Article
What causes Alzheimer's disease?
The cause(s) of Alzheimer's disease is (are) not known. The "amyloid cascade hypothesis" is the most widely discussed and researched hypothesis about the cause of Alzheimer's disease. The strongest data supporting the amyloid cascade hypothesis comes from the study of early-onset inherited (genetic) Alzheimer's disease. Mutations associated with Alzheimer's disease have been found in about half of the patients with early-onset disease. In all of these patients, the mutation leads to excess production in the brain of a specific form of a small protein fragment called ABeta (Aβ). Many scientists believe that in the majority of sporadic (for example, non-inherited) cases of Alzheimer's disease (these make up the vast majority of all cases of Alzheimer's disease) there is too little removal of this Aβ protein rather than too much production. In any case, much of the research in finding ways to prevent or slow down Alzheimer's disease has focused on ways to decrease the amount of Aβ in the brain.
What are risk factors for Alzheimer's disease?
The biggest risk factor for Alzheimer's disease is increased age. The likelihood of developing Alzheimer's disease doubles every 5.5 years from 65 to 85 years of age. Whereas only 1% to 2% of individuals 70 years of age have Alzheimer's disease, in some studies around 40% of individuals 85 years of age have Alzheimer's disease. Nonetheless, at least half of people who live past 95 years of age do not have Alzheimer's disease.
Common forms of certain genes increase the risk of developing Alzheimer's disease, but do not invariably cause Alzheimer's disease. The best-studied "risk" gene is the one that encodes apolipoprotein E (apoE). The apoE gene has three different forms (alleles) -- apoE2, apoE3, and apoE4. The apoE4 form of the gene has been associated with increased risk of Alzheimer's disease in most (but not all) populations studied. The frequency of the apoE4 version of the gene in the general population varies, but is always less than 30% and frequently 8% to 15%. People with one copy of the E4 gene usually have about a two- to three-fold increased risk of developing Alzheimer's disease. Persons with two copies of the E4 gene (usually around 1% of the population) have about a nine-fold increase in risk. Nonetheless, even persons with two copies of the E4 gene don't always get Alzheimer's disease. At least one copy of the E4 gene is found in 40% of patients with sporadic or late-onset Alzheimer's disease.
This means that in majority of patients with Alzheimer's disease, no genetic risk factor has yet been found. Most experts do not recommend that adult children of patients with Alzheimer's disease should have genetic testing for the apoE4 gene since there is no treatment for Alzheimer's disease. When medical treatments that prevent or decrease the risk of developing Alzheimer's disease become available, genetic testing may be recommended for adult children of patients with Alzheimer's disease so that they may be treated.
Many, but not all, studies have found that women have a higher risk for Alzheimer's disease than men. It is certainly true that women live longer than men, but age alone does not seem to explain the increased frequency in women. The apparent increased frequency of Alzheimer's disease in women has led to considerable research about the role of estrogen in Alzheimer's disease. Recent studies suggest that estrogen should not be prescribed to post-menopausal women for the purpose of decreasing the risk of Alzheimer's disease. Nonetheless, the role of estrogen in Alzheimer's disease remains an area of research focus.
Some studies have found that Alzheimer's disease occurs more often among people who suffered significant traumatic head injuries earlier in life, particularly among those with the apoE 4 gene.
In addition, many, but not all studies, have demonstrated that persons with limited formal education - usually less than eight years - are at increased risk for Alzheimer's disease. It is not known whether this reflects a decreased "cognitive reserve" or other factors associated with a lower educational level.
Medically Reviewed by a Doctor on 3/20/2015
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