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Wednesday, July 13, 2011

An Expert’s Advice on Symptoms of Alzheimer’s Disease


An Alzheimer’s Disease Doctor Answers Common Questions

By Colleen Davis Gardephe, Special to Lifescript

Published July 13, 2011

Reviewed by Edward C. Geehr, M.D.

“Plaques” and “tangles” are common terms doctors toss around when discussing symptoms of Alzheimer’s disease. But what are they, and when do they start to appear? A leading expert in Alzheimer’s diagnosis and treatment explains these key terms and talks about which genetic and lifestyle factors put you or your loved ones at risk…

Death rates from most major diseases have declined in the last 10 years, but not for Alzheimer’s disease. Mortality rates for the brain disorder jumped 66% from 2000-2008, according to the Alzheimer’s Association.

By 2030, 7.7 million people will have this degenerative, incurable form of dementia that destroys memory and eventually cognitive skills, the association predicts.

What triggers symptoms of Alzheimer’s? And if your mother had the disease, does it put you at higher risk?

Yes, according to Alan Jacobs, M.D., a leading specialist in Alzheimer’s treatment, memory disorders and neuroendocrinology who practices in New York.

“In general, if you have a first family member who had Alzheimer ’s disease, you’re 2-3 times more likely to get it yourself if you live to age 85,” he says.

In this exclusive Lifescript interview, Jacobs, a former Harvard and Cornell lecturer, discusses the causes and symptoms of Alzheimer’s and factors that can increase your risk.

What is Alzheimer’s disease?
Alzheimer’s disease causes problems with a person’s memory, thinking and behavior. Initially, a person may forget new information and, later, can become confused and irritable.

Eventually, the patient will have more serious memory loss and cognitive disability, and, at the end, experience physical changes, like difficulty swallowing, speaking and walking.

Alzheimer’s is thought to be the steady accumulation in the cerebral cortex of a protein called “beta-amyloid” – that [may] begin decades before clinical signs of overt memory loss appear, which is typically after age 65.

A person with Alzheimer’s has symptoms that develop slowly but become severe over time, so much so that they impede the person’s daily life.

What’s happening physiologically in an Alzheimer’s patient’s brain?
Dr. Aloysius “Alois” Alzheimer [who identified the symptoms of Alzheimer ’s disease in 1906] described abnormal clumps of a protein in the spaces between nerve cells. These are now called amyloid plaques.

He also described tangled fibers of another protein called tau (rhymes with wow) that build up inside cells. These are now called neurofibrillary tangles.

These plaques and tangles, along with the loss of nerve cell connections, are still the primary characteristics of the disease.

Which is a more important predictor of Alzheimer’s disease: plaques or tangles?
With modern imaging [techniques], it’s pretty safe to say that over a long presymptomatic stage occurring between the ages of 20 and 70, people accumulate amyloid first.

Eventually, tangles begin to form in a specific area of the brain called the entorhinal cortex, which is the gateway to the hippocampus, which controls memory. Once tangles appear, cells in this area start to die. That’s when a person becomes symptomatic with isolated insidious, progressive amnesia.

Tangles spread like wildfire through distinct pathways in the brain. That’s when the memory loss becomes accompanied with other clinical signs of the disease, like language and spatial/navigational troubles and then reasoning, and even behavioral/personality problems.

Can magnetic resonance imaging (MRI) or positron emission tomography (PET) scans detect plaques and tangles?
In the early stages of Alzheimer’s disease, an MRI won’t have a high enough resolution to see the development of plaques in the brain.

The Food and Drug Administration (FDA) recently approved use of a PET scan tracer that can image amyloid plaque in a living person. In the future, companies and doctors will use these scans to observe the development of amyloid because it’s a good biomarker for the presymptomatic phase of the disease, when treatment makes more sense.

Down the road, perhaps in a decade, people will probably be vaccinated against [the amyloid], or take a pill to prevent its accumulation of the amyloid.

Does family history increase the likelihood that you’ll develop Alzheimer’s?
Mutations in the genes for amyloid precursor protein (APP) presenilin-1 and presenilin-2 clearly lead to the familial early-onset form of Alzheimer’s disease, which can affect people in their 20s, 30s and 40s.

This group constitutes about 1 out of 10,000 people or families with the disease, so it is rare. Because it’s a simple model, this early onset version will probably be cured in the next 10 years.

But the general, sporadic form of the disease isn’t simple. [It’s] a massive web of complexity. They both take a person to Alzheimer’s.

The second group of genes involved in Alzheimer’s are disease-modifying or risk genes. We know of about five genes involved in the development of Alzheimer’s, with the APOE gene accounting for 30% or 40% of the genetic risk.

If a person has the APOE4 gene from one parent, their chance of getting Alzheimer’s increases 2-3 times. If they receive that gene from both parents, the risk climbs to 10 times normal.

What are some risk factors for developing symptoms of Alzheimer’s?
There’s a strong link between serious head injury and the development of Alzheimer’s.

If you have risk factors for heart disease, you may also [be at risk] for cerebral vascular disease, stroke, high blood pressure and high cholesterol, [which] are also risk factors for Alzheimer’s.

The connection between Alzheimer’s and diabetes is growing. If you have diabetes and high cholesterol in midlife, you are [also] more likely to get Alzheimer’s disease.

More and more research is linking insulin resistance in the brain to the further accumulation of amyloid.

The plaques and tangles in the brain are more likely to cause Alzheimer’s if there has been previous damage to the brain and its blood vessels from head trauma or a stroke.

Heavy drinking and a low education level are connected to increased risk for the disease as well.

Are some people less likely to develop symptoms of Alzheimer’s disease?
The more brain reserve you have, the more you can tolerate pathological signs of Alzheimer’s without showing the dementia.

People with high educational and occupational attainment who are physically fit have more brain connections, which seem to give them increased resilience.

Does that mean they don’t accumulate as much amyloid? Or are their brains better at dealing with it?
No one has really proven what is happening [in the brain]. But we know these people get the disease at a lower rate or push the onset of it later, all of which is good.

Can a healthy diet delay the onset of Alzheimer’s disease?
I don’t think it’s a matter of eating a particular food and protecting yourself from Alzheimer’s disease.

On the other hand, if you gain a lot of weight and develop diabetes in midlife, you’re stacking the deck against yourself and increasing the likelihood that you will get the disease sooner rather than later, say at 65 rather than 85.

To enhance your odds of not getting the disease, adopt a diet consisting of colorful fruits and vegetables and foods with plenty of antioxidants. It makes sense to consume less red meat and fewer processed foods, and reduce sugar consumption.

Eating three fish meals a week does seem to correlate with a lower risk of Alzheimer’s because the docosahexaenoic acid (DHA) in the omega-3 fish oils [protects] the brain.

Is depression a precursor to Alzheimer’s?
Many people who start transitioning from mild cognitive impairment to mild dementia get apathy – what we call abulia, the “bump-on-a-log” syndrome.

They no longer care about things that were previously important to them, like going to Florida for the winter or maintaining their garden.

Generalists not as familiar with Alzheimer’s say, “That seems like depression. I’m going to treat this person with Prozac.”

I usually see these people a year later, when the Prozac has done nothing to help them, and then treat them effectively with a cholinesterase inhibitor like donepezil [Aricept].

Which medications are currently prescribed for Alzheimer’s patients?
There isn’t a cure for the disease, but we have two classes of drugs to treat the symptoms of Alzheimer’s.

Cholinesterase inhibitors prevent the breakdown of acetylcholine, a chemical messenger that is key to learning and memory. Of this group, the most commonly prescribed medicines are Aricept, Exelon and Razadyne.

The other class of drug includes only memantine, branded as Namenda. It is also used to improve memory and cognition.

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