Alzheimer’s disease begins at the synapse, the space where neurons connect. The biggest bad guy in this disease is a sticky protein called beta-amyloid. Either too much is made or not enough is cleared away, and as beta-amyloid accumulates, it creates a gooey clog in the synapse, preventing the neurons that meet there from communicating. As a result, the information those neurons carry can’t be transmitted or retrieved. The beta-amyloid “goo” prevents these two neurons from “talking” to each other. We notice this molecular event because we forget something.
When too much beta-amyloid causes the synapse to fail, we begin to see the symptoms of Alzheimer’s. There are many risk factors that can contribute to having too much beta-amyloid. What are these risk factors?
First, let’s imagine a seesaw-style scale and the risk factors, which each vary in weight, are being piled on one arm of the scale. When that arm hits the floor, we have Alzheimer’s.
Risk Factors
1. Age
The biggest risk factor for developing Alzheimer’s is age. For reasons we still don’t entirely understand, as we get older, we accumulate more beta-amyloid. The chances of being diagnosed with Alzheimer’s increase steadily as we age. Right now, the risk of Alzheimer’s doubles every year after the age of 65. About half of people who are 85 and older have Alzheimer’s.
2. Genetics
Another risk factor is genetics. There is a rare form of Alzheimer’s called Familial Alzheimer’s, which always begins well before the age of 65 (typically in the 40s and 50s) and runs in families, that is autosomal dominant. This means that a single genetic mutation causes the disease. Picture the seesaw scale again. Genetic mutation is the only risk factor on the scale, and the arm is sitting on the floor.
Scientists have discovered three genetic mutations that cause this early-onset Familial Alzheimer’s. All three of these mutations result in molecular changes that cause an excess of beta-amyloid.
But this type of genetic risk factor is relatively rare, accounting for only about 5%of Alzheimer’s cases. The contribution of genetic risk factors to the development of Alzheimer’s for the vast majority of cases weighs much less on the scale, tipping the arm only a little bit.
For example, ApoE4 is a known genetic risk factor for Alzheimer’s. Forty to 65% of people with Alzheimer’s carry at least one copy of this mutation. But you can have two copies of this mutation (one inherited from each parent) and not have the disease. Again, imagine the arm of the scale tipped a bit with each copy of this mutation, but the arm is still well above the floor. Likewise, you can have zero copies of ApoE4 but have Alzheimer’s. The arm of your scale would be free of ApoE4 but piled high with other risk factors that tipped the scale over, leading to expression of the disease.
3. Head Trauma
Prior experience with head trauma, especially if consciousness was lost, increases the risk of developing Alzheimer’s. Always wear a seat belt and helmets.
4. Diabetes
In a recent study out of Japan that looked at over 1000 men and women over the age of 60, it was found that people with diabetes (especially type 2) were twice as likely to develop Alzheimer’s. Researchers are now trying to understand the molecular mechanisms that link diabetes to Alzheimer’s. It’s thought that the link may be twofold.
Nerve cells require a lot of energy to do the work of communicating. They get this energy from oxygen and glucose in the blood. With diabetes, cells lose their ability to respond to insulin, the molecule that transports glucose from the blood into the neurons, and so neurons have to cope with less glucose. Diabetes also often leads to damaged blood vessels, which compromises the delivery of oxygen to the nerves in the brain. Neurons already struggling to communicate despite too much beta-amyloid may lose the battle if glucose and oxygen are deprived.
Think of the scale arm with a bunch of risk factors piled on it. It’s hovering above ground but fighting to maintain that position. Things aren’t looking good for that synapse, but it’s still managing to function. Those neurons are still able to talk to each other. We aren’t showing any symptoms of Alzheimer’s yet. Add diabetes, and less oxygen and glucose to provide the energy the neurons need, and the scale arm goes crashing to the ground. Now we have Alzheimer’s.
5. Cardiovascular Disease
Eighty percent of people with Alzheimer's disease also have cardiovascular disease. Scientists are trying to better understand the link between heart health and Alzheimer’s disease, but we do know a few things about this relationship.
Cholesterol drives the production of beta-amyloid. For a brain that is already struggling to keep beta-amyloid levels in check, high cholesterol can be a risk factor that tips the scale. Doctors prescribe statins for people diagnosed with Alzheimer’s to help keep cholesterol levels down.
Again, the neurons in your brain need a lot of oxygen to do their job. If you have high blood pressure and if you have plaques in your blood vessels, your blood vessels are less efficient at delivering this oxygen to your brain. Not enough oxygen can be the weight that tips the Alzheimer’s scale.
All the risk factors for heart disease (things like poor diet, lack of exercise) are also risk factors for Alzheimer’s. And this means that things like a healthy, Mediterranean diet (whole grains, red and purple fruits and vegetables, fish, nuts) and exercise may not only protect the heart, they may protect us from Alzheimer’s. In fact, in animal studies, exercise has been shown to clear beta-amyloid better than any pharmaceutical we know of. Think of diet and exercise as weights on the other arm of the scale.
There is currently no cure for Alzheimer’s, but understanding these risk factors offers us some good news. While we can’t do anything about getting older or the genes we’ve inherited from our parents, eating smart, keeping cholesterol levels and blood sugar low, exercising, wearing a helmet when bicycling or skiing, and wearing a seat belt in the car are among the things we can do to keep the arm of the Alzheimer’s scale from tipping to the ground.
Showing posts with label alzheimer disease. Show all posts
Showing posts with label alzheimer disease. Show all posts
Monday, February 27, 2012
Wednesday, October 12, 2011
Diabetes Doubles Alzheimer's Risk
People with diabetes are at increased risk of having a heart attack or stroke at an early age. But that’s not the only worry: Diabetes appears to dramatically increase a person’s risk of developing Alzheimer’s disease or other types of dementia later in life, according to a new study conducted in Japan.
In the study, which included more than 1,000 men and women over age 60, researchers found that people with diabetes were twice as likely as the other study participants to develop Alzheimer’s disease within 15 years. They were also 1.75 times more likely to develop dementia of any kind.
“It’s really important for the public health to understand that diabetes is a significant risk factor for all of these types of dementia,”says Rachel Whitmer, PhD, an epidemiologist in the research division of Kaiser Permanente Northern California, a nonprofit health-care organization based in Oakland, Calif.
Whitmer, who studies risk factors for Alzheimer’s but wasn’t involved in the new research, stresses that many questions remain about the link between diabetes and dementia. The new study was “well done” and provides“really good evidence that people with diabetes are at greater risk,” she says,“but we really need to look at other studies to find out why.”
What Factors Increase the Risk?
Diabetes could contribute to dementia in several ways, which researchers are still sorting out. Insulin resistance, which causes high blood sugar and in some cases leads to type 2 diabetes, may interfere with the body’s ability to break down a protein (amyloid) that forms brain plaques that have been linked to Alzheimer’s. High blood sugar (glucose) also produces certain oxygen-containing molecules that can damage cells, in a process known as oxidative stress.
In addition, high blood sugar—along with high cholesterol—plays a role in the hardening and narrowing of arteries in the brain. This condition, known as atherosclerosis, can bring about vascular dementia, which occurs when artery blockages (including strokes) kill brain tissue.
“Having high glucose is a stressor to the nervous system and to the blood vessels,” says David Geldmacher, MD, a professor of neurology at the University of Alabama at Birmingham. “The emerging information on Alzheimer’s disease and glucose shows us that we do need to remain vigilant on blood sugar levels as we get older.”
New and Improved Research
Studies dating back to the late 1990s have suggested that people with diabetes are more likely to develop Alzheimer’s disease and other types of dementia, but the research has been marred by inconsistent definitions of both diabetes and dementia.
The authors of the new study, led by Yutaka Kiyohara, MD, an environmental medicine researcher at Kyushu University, in Fukuoka, sought to address this weakness by using the gold standard of diabetes diagnosis, an oral glucose tolerance test. This involves giving a person a sugar-loaded drink after they have fasted for at least 12 hours, and then measuring how much glucose remains in their blood two hours later.
At the beginning of the study, the tests showed that 15% of the participants had full-fledged diabetes, while 23% had prediabetes, also known as impaired glucose tolerance.
During the next 15 years, 23% of the participants received a dementia diagnosis. Slightly less than half of those cases were deemed to be Alzheimer’s disease, with the remainder roughly split between vascular dementia and dementia due to other causes. (The diagnoses were confirmed with brain scans of living patients and brain autopsies in deceased patients.)
The link between diabetes and dementia risk persisted even after the researchers took into account several factors associated with both diabetes and dementia risk, such as age, sex, blood pressure, and body mass index.
The next step in the research, Whitmer says, will be to understand whether controlling blood sugar and reducing risk factors for type 2 diabetes also reduces dementia risk. She and her colleagues have several studies underway investigating these questions.
In the study, which included more than 1,000 men and women over age 60, researchers found that people with diabetes were twice as likely as the other study participants to develop Alzheimer’s disease within 15 years. They were also 1.75 times more likely to develop dementia of any kind.
“It’s really important for the public health to understand that diabetes is a significant risk factor for all of these types of dementia,”says Rachel Whitmer, PhD, an epidemiologist in the research division of Kaiser Permanente Northern California, a nonprofit health-care organization based in Oakland, Calif.
Whitmer, who studies risk factors for Alzheimer’s but wasn’t involved in the new research, stresses that many questions remain about the link between diabetes and dementia. The new study was “well done” and provides“really good evidence that people with diabetes are at greater risk,” she says,“but we really need to look at other studies to find out why.”
What Factors Increase the Risk?
Diabetes could contribute to dementia in several ways, which researchers are still sorting out. Insulin resistance, which causes high blood sugar and in some cases leads to type 2 diabetes, may interfere with the body’s ability to break down a protein (amyloid) that forms brain plaques that have been linked to Alzheimer’s. High blood sugar (glucose) also produces certain oxygen-containing molecules that can damage cells, in a process known as oxidative stress.
In addition, high blood sugar—along with high cholesterol—plays a role in the hardening and narrowing of arteries in the brain. This condition, known as atherosclerosis, can bring about vascular dementia, which occurs when artery blockages (including strokes) kill brain tissue.
“Having high glucose is a stressor to the nervous system and to the blood vessels,” says David Geldmacher, MD, a professor of neurology at the University of Alabama at Birmingham. “The emerging information on Alzheimer’s disease and glucose shows us that we do need to remain vigilant on blood sugar levels as we get older.”
New and Improved Research
Studies dating back to the late 1990s have suggested that people with diabetes are more likely to develop Alzheimer’s disease and other types of dementia, but the research has been marred by inconsistent definitions of both diabetes and dementia.
The authors of the new study, led by Yutaka Kiyohara, MD, an environmental medicine researcher at Kyushu University, in Fukuoka, sought to address this weakness by using the gold standard of diabetes diagnosis, an oral glucose tolerance test. This involves giving a person a sugar-loaded drink after they have fasted for at least 12 hours, and then measuring how much glucose remains in their blood two hours later.
At the beginning of the study, the tests showed that 15% of the participants had full-fledged diabetes, while 23% had prediabetes, also known as impaired glucose tolerance.
During the next 15 years, 23% of the participants received a dementia diagnosis. Slightly less than half of those cases were deemed to be Alzheimer’s disease, with the remainder roughly split between vascular dementia and dementia due to other causes. (The diagnoses were confirmed with brain scans of living patients and brain autopsies in deceased patients.)
The link between diabetes and dementia risk persisted even after the researchers took into account several factors associated with both diabetes and dementia risk, such as age, sex, blood pressure, and body mass index.
The next step in the research, Whitmer says, will be to understand whether controlling blood sugar and reducing risk factors for type 2 diabetes also reduces dementia risk. She and her colleagues have several studies underway investigating these questions.
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