What Causes Alzheimer's Disease and Who Gets It

by Paula Spencer Scott for caring.com:Short-term memory loss is one of the most noticeable signs of Alzheimer's disease. But the disease process usually begins before symptoms are noticed. To assess someone's risk of becoming one of the more than 5 million Americans with Alzheimer's, it's helpful to understand the risk factors that increase the odds of developing the condition.What is Alzheimer's, and who's at risk?Although certain basic lifestyle changes can help delay the onset of the disease in some people, the exact cause of Alzheimer's disease isn't yet understood. Alzheimer's is a progressive neurodegenerative brain disorder: Normal brain cell function is gradually destroyed, leading to irreversible declines in memory, cognition, and behavior. But what causes things to go awry remains unknown. It may be that Alzheimer's has several causes or that the interplay between genetic makeup and certain risk factors determines who's affected.How old is he or she?

• At lower risk: Under age 70
• At higher risk: Over age 85

Why age matters: Age is the most significant established risk factor for Alzheimer's disease. One in 7 people over age 71 has some form of dementia, and 2.4 million of these have Alzheimer's, according to the latest National Institutes of Health data. The percentage of people with Alzheimer's rises from just 2.3 percent of those ages 71 to 79 to 18 percent of those ages 80 to 89, and 29.7 percent of those 90 or older. Some estimates say as many as half of all people over age 85 have Alzheimer's disease.The total number of people with the disease doubles with every five-year age jump after age 65.Is it a he or a she?

• At lower risk: Men
• At higher risk: Women

Why gender matters: Because women live longer than men, on average, and Alzheimer's disease risk rises with age, more women than men develop it. In addition, some research indicates that a lack of estrogen after menopause may contribute to the fact that, overall, slightly more women are affected. Taking hormone-replacement therapy has not been shown to protect against Alzheimer's.Vascular dementia is more common in men than women, probably because more men develop contributing factors such as hypertension and vascular problems.Have any of his or her parents or siblings had Alzheimer's?

• At lower risk: No family history or known genetic predisposition
• At higher risk: A family history or known genetic predisposition

Why family history matters: People with a family history of Alzheimer's are more likely to develop the disease. The risk is thought to rise with each relative who had it.It's unknown, though, exactly how much of this association is due to genetic factors and how much is due to shared lifestyle factors. Most experts believe that some combination of the two is responsible. Even when an immediate family member has the disease, however, your increased risk is only slightly higher than if your family had no history of dementia.Up to 80 percent of Alzheimer's risk may have a genetic component, according to a 2006 study of more than 12,000 Swedish twin sets -- a greater influence than was previously thought. But having a relative with the disease does not doom a person to a similar fate; even among identical twins, when one male twin had it, almost half of the time the other twin did not. (Among female twins, the other twin developed Alzheimer's 60 percent of the time, a difference researchers attributed to the fact that women generally live longer than men.) If Alzheimer's were solely genetic, both twins would have developed the disease, and at about the same time.So far, only two types of genetic tests for Alzheimer's exist, and neither of these blood tests is currently recommended for routine use.

• One kind of genetic test identifies a person's risk of developing Alzheimer's disease but doesn't guarantee whether or not he'll develop the condition. Everyone inherits a form of the apolipoprotein (APOE) gene from each parent. Apolipoprotein helps carry cholesterol in the blood. Its three most common forms are APOE-e2, APOE-e3, and APOE-e4. Those who have two copies of APOE-e4 seem to be at the highest risk of getting Alzheimer's and of developing symptoms earlier in life. Having one copy of APOE-e4 also elevates the risk. Only about 15 percent of people carry the APOE-e4 form.

It's thought that APOE is only one of many genes involved in the disease process. For instance, while it's considered a strong risk factor, the APOE-e4 gene shows up in only about 40 percent of all people with Alzheimer's disease. Identifying other genes that may be involved is a focus of ongoing research. The National Institute on Aging is conducting an Alzheimer's Disease Genetics Study, which is currently recruiting sibling pairs. These pairs must both have developed Alzheimer's after age 60 and must have a third family member with or without the disease who's willing to undergo cognitive tests and blood sampling.

• A second type of existing genetic test for Alzheimer's disease can predict with certainty who develops one rare form of the disease. This is early-onset familial Alzheimer's disease, which strikes between the ages of 30 and 65 and stretches through multiple generations. It accounts for less than 5 percent of all cases.

Does he or she smoke?

• At lower risk: Nonsmokers, former smokers
• At higher risk: Current smokers

Why smoking matters: Evidence is growing that smoking raises the risk of developing Alzheimer's disease by as much as 50 percent. In late 2007, Dutch researchers who tracked almost 7,000 people age 55 or older for 7 years reported that current smokers were more likely to develop dementia than people who had never smoked or had quit. Interestingly, the effect was more pronounced for people who did not have the APOE-e4 gene (the type known to be most vulnerable to the disease). Smoking didn't raise the already elevated risk of Alzheimer's in those who had the APOE-e4 gene.It's thought that smoking damages the cardiovascular system and causes oxidative stress, both conditions that are associated with Alzheimer's.You may have heard that smoking protects against dementia -- which is a myth. This persistent idea grew out of flawed studies and because fewer people with Alzheimer's were smokers. But in fact smokers, tend to have shorter life spans and are less likely to live to the advanced ages at which Alzheimer's most often strikes.Does he or she have diabetes?

• At lower risk: No history of diabetes
• At higher risk: Those with type 2 diabetes

Why diabetes matters: People with type 2 diabetes have at least double the risk of developing Alzheimer's compared with people without diabetes. The risk was 65 percent higher for diabetics in 2006 data from the ongoing Religious Orders Study of priests and nuns. Some studies have found that the higher the blood sugar levels, the higher the dementia risk.The mechanics behind the Alzheimer's-diabetes link aren't certain, but this is an area of intensive research. The leading explanations:

• High blood sugar may cause vascular problems. It's known that diabetes can cause cardiovascular problems and strokes; reduced blood flow to the brain may cause small-vessel damage there that leads to vascular dementia (a type of dementia that can appear with Alzheimer's).
• Insulin resistance leads to inflammation that can damage the brain. Insulin resistance occurs in diabetics when their cells can't use insulin properly to move glucose from the blood to be used for cell energy. The pancreas then makes extra insulin to compensate, which builds up in the blood and creates inflammation, which damages brain cells.
• Insulin resistance in the brain disrupts the proper formation of neuron connections. The autopsied brains of people with Alzheimer's always show amyloid plaques, clumps of the protein beta amyloid, which ruin brain cell connections. It's been discovered that this substance destroys the brain cells' receptors for insulin, which is used by the brain to make new memories. This results in dementia and memory loss.

As evidence of a clear biochemical link between the two conditions grows more compelling, some are calling Alzheimer's disease "type 3 diabetes."There's also a likely genetic link between diabetes and Alzheimer's. People with diabetes who also have the APOE-e4 gene (the type that places a carrier at highest risk for Alzheimer's) were two-and-a-half times more likely to develop the disease, according to a 2008 National Institute on Aging study.Does he or she have a history of being overweight?

• At lower risk: Low BMI in midlife
• At higher risk: Overweight or obese in midlife

Why weight matters: Being overweight or obese as measured by body mass index is well associated with an increased risk of developing dementia. Men with the leanest body mass index (BMI) in their late 40s and mid-50s were the least likely to develop Alzheimer's in a 20-year study of more than 7,000 Swedes; those who were heaviest were most likely.This same study also later found that women who were overweight at 70 were more likely to develop Alzheimer's in the next 10 to 18 years.People who are overweight are more likely to have related health problems that are also linked to Alzheimer's, such as hypertension, high blood pressure, cardiovascular disease, and diabetes. A related risk factor is if someone was previously overweight but has had unexplained weight loss recently. Weight loss associated with dementia may begin six to ten years before other symptoms become obvious. Research isn't clear whether this is because of declining ability to prepare meals or is a function of the disease process.

• At lower risk: No injury
• At higher risk: Prior head injury, especially after age 50

Why head injury matters: Prior head injury -- even years earlier -- is linked with a greater risk of developing Alzheimer's, though it's not clear why. That's not to say that any youthful bump will lead to Alzheimer's. The injury itself isn't thought to directly cause the disease, although it may hasten the process. But the more severe the trauma, the greater the risk of developing Alzheimer's, according to a large study of World War II veterans. The most concerning are thought to be falls with head injuries that occur later in life.Was he or she a college graduate?

• At lower risk: Higher education 
• At higher risk: Lower education level

Why education matters: People with lower education levels are more often affected by Alzheimer's disease. Researchers theorize that longer education helps the brain develop stronger, denser, more complex connections between brain cells, creating more cognitive reserve. This positions the brain to be better able to withstand the abnormal stresses associated with Alzheimer's disease and compensate for the changes that occur.Does he or she consume a balanced, low-fat, vitamin-rich diet?

• At lower risk: Heart-healthy diet rich in antioxidants
• At higher risk: Eating high-fat foods and an unbalanced diet

Why diet matters: Although there's no "Alzheimer's-prevention diet," a growing body of research indicates that nutrition influences brain health and may protect against or postpone cognitive decline. Specifically, your overall risk of Alzheimer's may be lower if you consume:

• B vitamins: People who are folate (B-9) deficient may run triple the risk of developing dementia, according to recent South Korean data. Previous research showed vitamin B-12 to be protective.
• Vitamin E: Those who consume the highest dietary amounts of this antioxidant have a lower incidence of Alzheimer's. Vitamin E supplements have not been shown to have the same protective effect.
• Vitamin C: Another antioxidant, vitamin C, seems to have a protective effect in certain people, though possibly only in dietary form. Antioxidants counter the effects of oxidative stress, which is linked to nerve cell damage and death. Over-the-counter vitamin C supplements did not reduce Alzheimer's risk in a recent study of 2,969 people 65 and older.

A heart-healthy diet: People who consume a generally balanced diet that avoids too much fat and includes complex carbohydrates are less likely to develop conditions that are Alzheimer's risks, including obesity, diabetes, and cardiovascular disease.Does he or she exercise regularly?

• At lower risk: Active lifestyle
• At higher risk: Sedentary lifestyle

Why exercise matters: Regular exercise reduced the risk of dementia by as much as 40 percent in a 2006 study of nearly 2,000 people age 65 and older. This was the first study to factor in one's pre-existing physical condition. And those most frail at the start of the study showed the greatest protection against dementia if they exercised. The threshold that made a difference: physical activity for at least 15 minutes, three times a week. Exercise both lowers the risk of obesity and cardiovascular conditions linked to Alzheimer's and reduces the risk of developing dementia.Previous research has shown that the variety of activity engaged in is more important than the intensity of a workout, when it comes to providing brain benefits. (Variety of workouts had no benefit, though, to those with the APOE-e4 gene variation most commonly associated with Alzheimer's.)Does he or she engage in mentally stimulating activities?

• At lower risk: Varied, frequent "brain workouts"
• At higher risk: Lack of mental stimulation

Why mental stimulation matters: Just as physical activity exercises the body, "cognitive activity" exercises the brain. Numerous studies now support the "use it or lose it" idea that mental workouts lower the risk of dementia. For example, participants in the Religious Orders study who attended museums, worked puzzles, and read newspapers were 47 percent less likely to develop Alzheimer's after four years than those who did such activities less frequently.Brain-stretching activities can't prevent Alzheimer's, but they help the brain better withstand the physical changes associated with it. What's key: The stimulation should be ongoing.Is he or she socially stimulated?

• At lower risk: Social engagement
• At higher risk: Social isolation and loneliness

Why social stimulation matters: Isolation is a risk factor for developing dementia, probably because there's less opportunity for mental stimulation. But a surprising 2007 study also found that people who were around others but felt lonely (emotional isolation) were also at higher risk for Alzheimer's. This sense of loneliness wasn't a result of the disease (as is often the case with depression) but a clear precursor.Source: http://www.caring.com/articles/exercise-and-engagement-alzheimers-risk