April 8, 2010
Will you get Alzheimer's in old age? If you live past age 85, chances are better than one in three that you will. And having Alzheimer's in your family and other factors can further increase your risk.
Alzheimer's disease affects a growing number of men and women, with 5.5 million cases in the United States and more than 35 million worldwide. An estimated 13 to 16 million Americans will have Alzheimer's by 2050. And while scientists have made great strides in understanding the underlying mechanisms of the disease, much research still needs to be done to better understand the causes of Alzheimer's, find effective treatments and, ultimately, a cure.
Alzheimer's disease is the most common form of dementia, accounting for more than half of cases. In another 15 percent or so of cases, Alzheimer's is present along with blood vessel disease in the brain.
A review article in The New England Journal of Medicine underlines that age is the main risk factor for late-onset Alzheimer's, by far the most common form of the disease. About 1,275 people out of every 100,000 seniors age 65 and over are given a diagnosis of Alzheimer's each year, and the incidence of disease doubles every 5 years after age 65. Loss of memory and thinking skills declines as the disease progresses, with death occurring some three to nine years after diagnosis.
Studies of people who remain mentally sharp to age 100 and beyond, however, show that Alzheimer's is not an inevitable result of aging. Many other factors also play a role in who gets Alzheimer's.
Scientists have identified genes, for example, that cause family member to get Alzheimer's at age 40 or younger. They have found other genes, like APOE-E4, that increase the risk (but by no means guarantee) that older people will develop the far more common sporadic form of Alzheimer's that crops up later in life. Inheriting one copy of APOE-E4 from a parent increases the risk of Alzheimer's by 4-fold. Inheriting two copies from both parents increases the risk 19-fold. Many more genes are under investigation.
Scientists are also studying a wide range of proteins in the brain that seem to go awry in Alzheimer's. Chief among these is beta-amyloid, a protein that in its toxic form builds up in the brains of those with Alzheimer's. Various proteins and enzymes seem to affect beta-amyloid, causing it to accumulate. Scientists are looking for drugs or vaccines that may stem the buildup of beta-amyloid. Tau, a protein that forms tangles inside affected brain cells, is also a target of new therapeutic strategies. Inflammation, the generation of highly reactive oxygen molecules called free radicals, and other factors may likewise play a role in Alzheimer's.
In addition, researchers are looking at various groups of people who may be at increased risk for Alzheimer's to better understand what goes wrong in the disease. People who undergo general anesthesia, for example, may be at increased risk for Alzheimer's. Declining levels of the sex hormone estrogen in the brains of women after menopause may increase risk, and the genetic disease Down syndrome increases risk. And after age 80, shrinkage in brain size may contribute to disease onset. By better understanding these varied pathways to Alzheimer's, scientists hope to uncover new ways of combating it.
Finally, evidence continues to build that engaging in mentally challenging activities like word games or crossword puzzles or learning a new language or musical instrument may help to build up "brain reserve." According to this theory, cognitive challenges help to strengthen connections between brain cells throughout life. If brain cells are lost to the effects of Alzheimer's, the brain may compensate with these robust connections and stay vital into old age.
The Fisher Center for Alzheimer's Research Foundation funds critical research into the underlying mechanisms of Alzheimer's. Only through such basic research can scientists hope to develop new strategies for dealing with the disease. To learn more, visit www.ALZinfo.org, the Alzheimer's Information Site.
Henry W. Querfurth, M.D., Ph.D., Frank M. LaFerla, Ph.D., "Mechanisms of Disease: Alzheimer's Disease," (Review). The New England Journal of Medicine, Vol. 362, Jan. 28, 2010, pages 329-244.