You may have forgotten where you put your car keys, or can’t seem to remember the name of the colleague you saw in the grocery store the other day. You fear the worst; maybe these are signs of Alzheimer’s disease.
You’re not alone. A recent study asking Americans aged 60 or older the condition they were most afraid of getting indicated the number-one fear was Alzheimer’s or dementia (35 percent), followed by cancer (23 percent) and stroke (15 percent).
And, when we hear of someone like legendary University of Tennessee women’s basketball Coach Pat Summitt dying (on June 28) from early-onset Alzheimer’s at age 64, fears are heightened.
Memory loss is normal; Alzheimer’s is not
Alzheimer’s is an irreversible, progressive brain disease that slowly destroys memory and thinking skills, leading to cognitive impairment that severely affects daily living. Often the terms Alzheimer’s and dementia are used interchangeably, and although the two are related, they are not the same. Dementia is a general term for the loss of memory or other mental abilities that affect daily life. Alzheimer’s is a cause of dementia, with over 70 percent of all dementia cases occurring as a result of Alzheimer’s.
The majority of Alzheimer’s cases occur in people 65 or older.
Slight memory loss is a normal consequence of aging, and, therefore, people, should not be overly concerned if they lose their keys or forget the name of a neighbor at the grocery store. If these things happen infrequently, there is scant reason to worry. You most likely do not have Alzheimer’s if you simply forgot one time where you parked upon leaving Disneyland, or the local mall during the holidays.
A key point to consider is whether these symptoms significantly affect daily living. If so, then Alzheimer’s disease might be the cause.
People frequently ask if they might be more apt to be afflicted with the disease if a grandparent had it. Again, the majority of cases occur in people 65 or older. In such late-onset cases, the cause of the disease is unknown (e.g. sporadic), although advancing age and inheriting certain genes may play an important role. Importantly, although there are several known genetic risk factors associated with late-onset Alzheimer’s, inheriting any one of these genes does not assure a prognosis of the disorder as one advances in age.
Early-onset is rare, but heredity does play an important role
In fact, less than five percent of five million cases cited were a direct result of hereditary mutations (e.g. familial form of Alzheimer’s). Inheriting these rare, genetic mutations leads to what is known as early-onset Alzheimer’s, which is characterized by symptoms often detected in one’s 40s and 50s, and is a more aggressive form of the disease; one that leads to a more rapid decline in memory impairment and cognition.
In general, most neurologists agree that the early-onset and late-onset forms are essentially the same disease, apart from the differences in genetic cause and age at onset. The one exception is the prevalence of a condition called myoclonus (characterized by muscle twitching and spasms) that is more commonly observed in the early-onset version.
In addition, some studies suggest that people with the early-onset type decline at a faster rate than those with late-onset. Even though, generally speaking, the two forms are medically equivalent, the large burden early-onset poses on the family is quite evident. Often these patients are still in the most productive phases of their life, and yet the onset of the disease robs them of brain function. These individuals may still be physically fit and active when diagnosed, and more often than not still have family and career responsibilities. Therefore, a diagnosis may have a greater negative, ripple effect on the patient, as well as family members.
Although the genes giving rise to “early-onset” are extremely rare, these inherited mutations do run in families worldwide, and the study of them has provided critical knowledge about the molecular underpinnings of the disease. These familial forms result from mutations that are typically defined as being autosomal dominant, meaning there needs only to be one parent that passes the gene on to their child. If this happens, there is no escape from an eventual Alzheimer’s diagnosis.
What scientists have learned from these rare mutations is that in every case they lead to the overproduction of a rogue, toxic, protein, beta-amyloid. Its build-up in the brain produces plaques that are one of the hallmarks of the disease. Just as plaques in arteries can harm the heart, plaques on the brain can have dire consequences for brain function.
By studying families with early-onset, scientists now realize that the buildup of beta-amyloid can happen decades before the first symptoms of the disease manifest. This gives scientists tremendous hope in terms of a large therapeutic window to intervene and stop the beta-amyloid cascade.
Hope is high for large trial underway
Indeed, one of the most anticipated clinical trials underway at this moment involves a large Colombian family of over 5,000 members who may carry an early-onset Alzheimer’s gene. Three hundred family members will participate in this trial in which half are young, and years away from symptoms, but who have the Alzheimer’s gene. They will receive a drug that has been shown to decrease the production of beta-amyloid. The other half will take a placebo, and will comprise the control group.
Neither patient nor doctor will know whether they will be receiving the active drug, which helps eliminate potential biases. The trial will last five years, and although it will involve a small percentage of people with early-onset Alzheimer’s, the information from the trial could be applied to millions of people worldwide who will develop the more conventional, late-onset form.
Currently, there are no effective treatments or cure for Alzheimer’s, and the only medications available are palliative in nature. What is critically needed are disease-modifying drugs; drugs that actually stop the beta-amyloid in its tracks. Devastating as early-onset Alzheimer’s is, there is hope that prevention trials as described above could ultimately lead to effective treatments for this insidious disease in the near future.
Troy Rohn, Professor of Biology, Boise State University.