Phyllis Schweitzer is in the early to middle stages of Alzheimer’s disease and is surrounded by family in her home. Michele (17), Phyllis’s granddaughter hangs out with her grandmother after dinner.
The New York Times, September 12, 2011, by Gina Kolata — A small pilot study has found preliminary evidence that squirting insulin deep into the nose where it travels to the brain might hold early Alzheimer’s disease at bay, researchers said on Monday.
It comes at a time when there are no effective ways to prevent or delay the progress of Alzheimer’s. And although the results are preliminary and must be viewed with caution, “it is a provocative study,” said Dr. Jason Karlawish, an Alzheimer’s researcher and ethicist at the University of Pennsylvania. But he and other experts caution that a bigger and longer study is needed to see if the initial results hold up and whether there are adverse effects that might negate any benefits.
“It’s important readers realize this is a pilot trial,” said Dr. P. Murali Doraiswamy, an Alzheimer’s researcher at Duke University who was not part of the study. “It’s not ready for prime time.”
The study, published online in the Annals of Neurology, included 104 people, a group small enough that the promising results could have occurred by chance.
Researchers at the University of Washington divided the subjects into three groups. One got a placebo, one got 20 international units of aerosolized insulin a day, and the third got 40 international units a day.
In the four-month study, the group randomly assigned to receive intranasal insulin twice a day either improved slightly or remained the same in tests of memory and assessments of their ability to handle day-to-day activities. The lower dose seemed more effective than the higher one. Those who received placebos got worse.
A third also had scans to assess their brains’ use of glucose. One hallmark of Alzheimer’s disease is reduced metabolism in the brain, which shows up on scans as less use of glucose, the fuel for brain cells. In this assessment, those getting insulin used more glucose in their brains; those taking placebos used less.
For years, the study’s principal investigator, Suzanne Craft, has studied insulin’s effects in Alzheimer’s. She is professor of psychiatry at the University of Washington in Seattle and director of the memory disorders clinic at the Veterans Affairs Puget Sound Health Care System.
Brain cells need insulin, Dr. Craft said. And conditions in which the body makes too little insulin or is resistant to its effects — diabetes, prediabetes, even untreated high-blood pressure — are associated with an increased risk of Alzheimer’s.
In addition, she said, beta amyloid, a toxic protein that accumulates in the brain of Alzheimer’s patients, seems to tie up insulin in the brain.
So, Dr. Craft reasoned, perhaps if more insulin could be put into the brains of people with the degenerative brain disease, their memories and ability to function might improve. The problem was to find a way to get more insulin to the brain but not to the body.
The solution was a special device made by Kurve Technology that delivers a spray of insulin deep into the nose. From there the hormone travels along the path of nerves into the brain.
The investigators first tried a single dose of insulin delivered via nasal spray to the brains of people with Alzheimer’s disease. Their memories improved temporarily. Then they tried giving insulin daily for three weeks. Again, the hormone seemed to help. That led to the current study, lasting four months.
But Dr. Martha Daviglus of Northwestern University, who led a panel last year that assessed published papers on preventing and treating Alzheimer’s, urged caution. In her field, cardiovascular medicine, she has seen many exciting findings in small studies that fall apart in larger or longer ones.
Now Dr. Craft wants to test insulin again in a much more extensive study. .
In the meantime, she cautions Alzheimer’s patients not to rush out and try to take insulin. It is too soon to say if the treatment is even safe, she said. And patients would need a special device to get it deep into the nose. Kurve’s device is not yet on the market.
“The individual person will not be able to get this device,” Dr. Craft said. But, she added, if her study goes forward, many will be able to participate in it.
For Edge on Alzheimer’s, Testing Early Treatments
Researchers are trying to determine when and how the brain begins to deteriorate. Above, Carlos Alberto Villegas, a patient, is looked after by his grandson
The New York Times, by Pam Belluck — Much of the research on Alzheimer’s next year will be about going back in time, trying to determine when and how the brain begins to deteriorate.
Scientists now know Alzheimer’s attacks the brain long before people exhibit memory loss or cognitive decline. But the specifics are crucial because so far, drug after drug has failed to effectively treat Alzheimer’s in people who already show symptoms. Many scientists now think the problem may be that the drugs were given too late, when, as Dr. John C. Morris, an Alzheimer’s expert at Washington University in St. Louis, puts it, “there’s a heck of a lot of brain cell damage and we’re trying to treat a very damaged brain.”
If drugs could be given sooner, tailored to specific biological changes, or biomarkers, in the brain, treatment, or even prevention, might be more successful.
“We’re trying to go earlier and earlier in the course of the disease,” said Neil Buckholtz, chief of the Dementias of Aging branch at the National Institute on Aging. “The idea is to locate how people move through these stages and what indications there are of each stage.”
Several research projects are expecting to make strides next year.
One involves the world’s largest family to experience Alzheimer’s disease, an extended clan of about 5,000 people in Colombia, many of whom have inherited a genetic mutation that guarantees they will develop dementia, usually in their 40s. Except for its clear genetic cause and that it strikes people so young, the Colombian condition is virtually identical in its disease process to more common Alzheimer’s, which has unknown causes and afflicts millions of elderly people.
A team of American and Colombian scientists plans to test treatments on Colombians in their late 30s and early 40s who are destined to get Alzheimer’s but have not yet developed symptoms to see if dementia can be prevented or significantly delayed. The treatment, to be chosen by an independent panel, will be a drug or vaccine that attacks beta-amyloid, the protein associated with plaques, deposits between nerve cells. A project leader, Dr. Eric Reiman, director of the Banner Alzheimer’s Institute in Phoenix, said testing on as many as 2,000 people, including about 750 with the mutation, is likely to begin late 2011 or early in 2012.
Meanwhile, the project, begun this year, has had some tantalizing findings. To try to find the youngest age at which brain changes appear, brain scans, spinal taps and memory tests were conducted with 44 family members, ages 18 to 26.
While Dr. Reiman said he could not discuss specific data yet, the tests showed enough evidence of Alzheimer’s-related biomarkers on people with the mutation that fMRI brain scans will be done on even younger family members, ages 8 to 17. If the scans reveal children with the mutation have Alzheimer’s-like anomalies, like atrophy in the hippocampus, which is involved in forming new memories, that would suggest the brain begins transforming decades before symptoms appear.
To examine when beta-amyloid begins accumulating, the project will also conduct amyloid imaging on an additional 50 family members, age 18 and older.
The team, also led by Dr. Pierre Tariot of the Banner institute and Dr. Francisco Lopera, who is at the University of Antioquia in Medellin, also plans to test drug treatments on an unrelated group: 60- to 80-year-old Americans with a different rare trait: two copies of the ApoE4 gene, which does not cause but increases risk of common Alzheimer’s.
A different project, the Dominantly Inherited Alzheimer Network, or DIAN, led by Dr. Morris, is studying members of families in the United States, Australia and Britain who have mutations that cause dementia at age 46, on average. DIAN has recruited 100 people, 18 and older, whose parents had Alzheimer’s-causing mutations but who do not yet show symptoms; it plans to recruit 300 more. So far, researchers have found evidence that “biomarker changes do seem to occur at least 10 years, maybe 20 years before the age of onset” of symptoms, Dr. Morris said.
DIAN also plans to test drugs on participants, hopefully within three years, and is talking with companies, which are interested, but need assurance that testing drugs on apparently healthy people, those without symptoms, is worth the investment and potential risk, Dr. Morris said.
The Colombia and DIAN projects are “really the first time companies have come to grips with this,” said Dr. Morris, who believes Alzheimer’s is so complex that a combination of drugs will be needed to attack different biomarkers.
Another project looking for early signs is the Alzheimer’s Disease Neuroimaging Initiative, or ADNI, a collaboration of government and industry, involving scientists at 55 research sites in the United States and Canada. It has been following about 800 people for about six years and has yielded significant findings about changes in the hippocampus, and about screening for Alzheimer’s proteins with PET scans and spinal fluid tests.
ADNI will recruit 550 more participants, including many with budding memory loss called early mild cognitive impairment.
They will be, Dr. Buckholtz said, “not quite as sharp as they were previously, but not to the point where they are really forgetting.”
New Test may Predict Alzheimer’s Early: Study
GoogleNews.com, MedlinePlus.gov, Summer/Fall 2011, by Julie Steenhuysen – A new way of testing for signs of Alzheimer’s disease in spinal fluid may help more accurately identify which people with mild memory deficits will progress to full-blown dementia, researchers reported on Wednesday.
The findings, released in the journal Neurology, are part of a push to find new ways to diagnose Alzheimer’s early, before the disease causes too much harm.
“Being able to identify who will develop Alzheimer’s disease very early in the process will be crucial in the future,” Dr. Robert Perneczky of the Technical University Munich in Germany, who led the study.
“Once we have treatments that could prevent Alzheimer’s disease, we could begin to treat very early and hopefully prevent the loss of memory and thinking skills that occurs with this devastating disease.”
Current spinal fluid tests for Alzheimer’s look for an imbalance in two proteins: beta amyloid, which forms sticky plaques in the brain, and tau, which is seen as a marker of brain cell damage.
People with Alzheimer’s tend to have lower levels of beta amyloid and higher levels of tau protein in their spinal fluid, and doctors often test for this to confirm the dementia is caused by Alzheimer’s.
In the study, Perneczky and colleagues looked for remnants of a key building block of beta amyloid called amyloid precursor protein or APP.
“If you are cutting out a cookie, it’s the dough around the cookie that’s left behind,” said Dr. Marc Gordon, an Alzheimer’s researcher at The Feinstein Institute for Medical Research in Manhasset, New York.
“That is what they were measuring here,” said Gordon, who was not involved with the study.
The researchers collected spinal fluid from 58 people with slight memory problems, or mild cognitive impairment, a condition that often progresses to Alzheimer’s.
After three years, 21 people had developed Alzheimer’s, 27 still had mild cognitive impairment, eight people had reverted back to their normal cognitive health, and two others developed a condition called frontotemporal dementia and were excluded from the analysis.
The study showed that people who progressed to Alzheimer’s had significantly higher levels of this remnant of APP called soluble amyloid precursor protein beta in their spinal fluid than those who did not develop Alzheimer’s.
When combined with other biomarkers, such as the presence of tau and a person’s age, the test was roughly 80 percent accurate in predicting whether the disease would develop.
And they found that the form of beta amyloid normally used to test for Alzheimer’s was not a good predictor of which patients with mild impairments might progress to dementia.
While the study is very early, Gordon said tests like this will be needed as companies try to develop treatments for Alzheimer’s that can keep the disease from progressing.
Some 26 million people have Alzheimer’s, a fatal disease that is the most common form of dementia. Current drugs only help symptoms, but no drug can arrest Alzheimer’s, which costs $604 billion a year to treat.
The New York Times Medical Reference — Dementia is a loss of brain function that occurs with certain diseases. Alzheimer’s disease (AD), is one form of dementia that gradually gets worse over time. It affects memory, thinking, and behavior.
Memory impairment, as well as problems with language, decision-making ability, judgment, and personality, are necessary features for the diagnosis.
Age and family history are risk factors for AD.
- As you get older, your risk of developing AD goes up. However, developing Alzheimer’s disease is not a part of normal aging.
- Having a close blood relative, such as a brother, sister, or parent who developed AD increases your risk.
- Having certain combination of genes for proteins that appear to be abnormal in Alzheimer’s disease also increases your risk.
Other risk factors that are not as well proven include:
- Longstanding high blood pressure
- History of head trauma
- Female gender
There are two types of AD — early onset and late onset.
- In early onset AD, symptoms first appear before age 60. Early onset AD is much less common than late onset. However, it tends to progress rapidly. Early onset disease can run in families. Several genes have been identified.
- Late onset AD, the most common form of the disease, develops in people age 60 and older. Late onset AD may run in some families, but the role of genes is less clear.
The cause of AD is not entirely known, but is thought to include both genetic and environmental factors. A diagnosis of AD is made when certain symptoms are present, and by making sure other causes of dementia are not present.
The only way to know for certain that someone has AD is to examine a sample of their brain tissue after death. The following changes are more common in the brain tissue of people with AD:
- “Neurofibrillary tangles” (twisted fragments of protein within nerve cells that clog up the cell)
- “Neuritic plaques” (abnormal clusters of dead and dying nerve cells, other brain cells, and protein)
- “Senile plaques” (areas where products of dying nerve cells have accumulated around protein).
When nerve cells (neurons) are destroyed, there is a decrease in the chemicals that help nerve cells send messages to one another (called neurotransmitters). As a result, areas of the brain that normally work together become disconnected.
The buildup of aluminum, lead, mercury, and other substances in the brain is no longer believed to be a cause of AD.
Dementia symptoms include difficulty with many areas of mental function, including:
- Emotional behavior or personality
- Cognitive skills (such as calculation, abstract thinking, or judgment)
Dementia usually first appears as forgetfulness.
Mild cognitive impairment is the stage between normal forgetfulness due to aging, and the development of AD. People with MCI have mild problems with thinking and memory that do not interfere with everyday activities. They are often aware of the forgetfulness. Not everyone with MCI develops AD.
Symptoms of MCI include:
- Forgetting recent events or conversations
- Difficulty performing more than one task at a time
- Difficulty solving problems
- Taking longer to perform more difficult activities
The early symptoms of AD can include:
- Language problems, such as trouble finding the name of familiar objects
- Misplacing items
- Getting lost on familiar routes
- Personality changes and loss of social skills
- Losing interest in things previously enjoyed, flat mood
- Difficulty performing tasks that take some thought, but used to come easily, such as balancing a checkbook, playing complex games (such as bridge), and learning new information or routines
As the AD becomes worse, symptoms are more obvious and interfere with your ability to take care of yourself. Symptoms can include:
- Forgetting details about current events
- Forgetting events in your own life history, losing awareness of who you are
- Change in sleep patterns, often waking up at night
- Difficulty reading or writing
- Poor judgment and loss of ability to recognize danger
- Using the wrong word, mispronouncing words, speaking in confusing sentences
- Withdrawing from social contact
- Having hallucinations, arguments, striking out, and violent behavior
- Having delusions, depression, agitation
- Difficulty doing basic tasks, such as preparing meals, choosing proper clothing, and driving
People with severe AD can no longer:
- Understand language
- Recognize family members
- Perform basic activities of daily living, such as eating, dressing, and bathing
Other symptoms that may occur with AD:
- Swallowing problems
AD can often be diagnosed through a history and physical exam by a skilled doctor or nurse. A health care provider will take a history, do a physical exam (including a neurological exam), and perform a mental status examination.
Tests may be ordered to help determine whether other medical problems could be causing dementia or making it worse. These conditions include:
- Thyroid disease
- Vitamin deficiency
- Brain tumor
- Intoxication from medication
- Chronic infection
- Severe depression
- In the early stages of dementia, brain image scans may be normal. In later stages, an MRI may show a decrease in the size of different areas of the brain.
- While the scans do not confirm the diagnosis of AD, they do exclude other causes of dementia (such as stroke and tumor).
Unfortunately, there is no cure for AD. The goals in treating AD are to:
- Slow the progression of the disease (although this is difficult to do)
- Manage behavior problems, confusion, sleep problems, and agitation
- Modify the home environment
- Support family members and other caregivers
Most drugs used to treat Alzheimer’s are aimed at slowing the rate at which symptoms become worse. The benefit from these drugs is often small, and patients and their families may not always notice much of a change.
Patients and caregivers should ask their doctors the following questions about whether and when to use these drugs:
- What are the potential side effects of the medicine and are they worth the risk, given that there will likely be only a small change in behavior or function?
- When is the best time, if any, to use these drugs in the course of Alzheimer’s disease?
Two types of medicine are available:
- Donepezil (Aricept), rivastigmine (Exelon), and galantamine (Razadyne, formerly called Reminyl) affect the level of a chemical in the brain called acetylcholine. Side effects include indigestion, diarrhea, loss of appetite, nausea, vomiting, muscle cramps, and fatigue.
- Memantine (Namenda) is another type of drug approved for treating AD. Possible side effects include agitation or anxiety.
Other medicines may be needed to control aggressive, agitated, or dangerous behaviors. These are usually given in very low doses.
It may be necessary to stop any medications that make confusion worse. Such medicines may include painkillers, cimetidine, central nervous system depressants, antihistamines, sleeping pills, and others. Never change or stop taking any medicines without first talking to your doctor.
Many people take folate (vitamin B9), vitamin B12, and vitamin E. However, there is no strong evidence that taking these vitamins prevents AD or slows the disease once it occurs.
Some people believe that the herb ginkgo biloba prevents or slows the development of dementia. However, high-quality studies have failed to show that this herb lowers the chance of developing dementia. DO NOT use ginkgo if you take blood-thinning medications like warfarin (Coumadin) or a class of antidepressants called monoamine oxidase inhibitors (MAOIs).
If you are considering any drugs or supplements, you should talk to your doctor first. Remember that herbs and supplements available over the counter are NOT regulated by the FDA.
For additional information and resources for people with Alzheimer’s disease and their caregivers, see Alzheimer’s disease support groups.
How quickly AD gets worse is different for each person. If AD develops quickly, it is more likely to worsen quickly.
Patients with AD often die earlier than normal, although a patient may live anywhere from 3 – 20 years after diagnosis.
The final phase of the disease may last from a few months to several years. During that time, the patient becomes immobile and totally disabled.
Death usually occurs from an infection or a failure of other body systems.
- Loss of ability to function or care for self
- Bedsores, muscle contractures (loss of ability to move joints because of loss of muscle function), infection (particularly urinary tract infections and pneumonia), and other complications related to immobility during end stages of AD
- Falls and broken bones
- Loss of ability to interact
- Malnutrition and dehydration
- Failure of body systems
- Harmful or violent behavior toward self or others
- Abuse by an over-stressed caregiver
When to Contact a Medical Professional
Call your health care provider if someone close to you experiences symptoms of senile dementia/Alzheimer’s type.
Call your health care provider if a person with this disorder experiences a sudden change in mental status. (A rapid change may indicate other illness.)
Discuss the situation with your health care provider if you are caring for a person with this disorder and the condition deteriorates to the point where you can no longer care for the person in your home.
Although there is no proven way to prevent AD, there are some practices that may be worth incorporating into your daily routine, particularly if you have a family history of dementia. Talk to your doctor about any of these approaches, especially those that involve taking a medication or supplement.
- Consume a low-fat diet.
- Eat cold-water fish (like tuna, salmon, and mackerel) rich in omega-3 fatty acids, at least 2 to 3 times per week.
- Reduce your intake of linoleic acid found in margarine, butter, and dairy products.
- Increase antioxidants like carotenoids, vitamin E, and vitamin C by eating plenty of darkly colored fruits and vegetables.
- Maintain a normal blood pressure.
- Stay mentally and socially active throughout your life.
- Consider taking nonsteroidal anti-inflammatory drugs (NSAIDs) like ibuprofen (Advil, Motrin), sulindac (Clinoril), or indomethacin (Indocin). Statin drugs, a class of medications normally used for high cholesterol, may help lower your risk of AD. Talk to your doctor about the pros and cons of using these medications for prevention.
In addition, early testing of a vaccine against AD is underway.
The Biology of Alzheimer’s Disease
Alzheimer’s and Stem Cell Research
A Plan to Eradicate Alzheimer’s Disease
Alzheimer’s: Life-Style Risk Factors
Alzheimer’s: From Genes to Novel Therapeutics
FierceBiotech.com, Posted September 12, 2011
COLUMBIA, Mo. -Many older adults lose their independence as their health declines and they are compelled to move into assisted care facilities. Researchers at the University of Missouri and TigerPlace, an independent living community, have been using motion-sensing technology to monitor changes in residents’ health for several years. Now, researchers have found that two devices commonly used for video gaming and security systems are effective in detecting the early onset of illness and fall risk in seniors.
Marjorie Skubic, professor of electrical and computer engineering in the MU College of Engineering, is working with doctoral student, Erik Stone, to use the Microsoft Kinect, a new motion-sensing camera generally used as a video gaming device, to monitor behavior and routine changes in patients at TigerPlace. These changes can indicate increased risk for falls or early symptoms of illnesses.
“The Kinect uses infrared light to create a depth image that produces data in the form of a silhouette, instead of a video or photograph,” said Stone. “This alleviates many seniors’ concerns about privacy when traditional web camera-based monitoring systems are used.”
Another doctoral student, Liang Liu, is collaborating with Mihail Popescu, assistant professor in the College of Engineering and the Department of Health Management and Informatics in the MU School of Medicine, to develop a fall detection system that uses Doppler radar to recognize changes in walking, bending and other movements that may indicate a heightened risk for falls. Different human body parts create unique images, or “signatures,” on Doppler radar. Since falls combine a series of body part motions, the radar system can recognize a fall based on its distinct “signature.”
“Falls are especially dangerous for older adults and if they don’t get help immediately, the chances of serious injury or death are increased,” said Liu. “If emergency personnel are informed about a fall right away, it can significantly improve the outcome for the injured patient.”
Both motion-sensing systems provide automated data that alert care providers when patients need assistance or a medical intervention. The systems currently are used for monitoring residents at TigerPlace in Columbia. Skubic says the system allows residents to maintain their independence and take comfort in knowing that illnesses or falls may be detected early.
Stone’s study, “Evaluation of an Inexpensive Depth Camera for Passive In-Home Fall Risk Assessment,” won the best paper award at the Pervasive Health Conference, in Dublin, Ireland in May. Liu’s study, “Automatic Fall Detection Based on Doppler Radar Motion,” received the best poster award at the conference. Liu’s paper was a collaboration with GE Global Research and co-authored by Tarik Yardibi and Paul Cuddihy. TigerPlace is a joint project of the Sinclair School of Nursing and AmErikare, a long-term care company. For more information about MU’s interdisciplinary eldercare technology research, visit http://eldertech.missouri.edu or www.agingmo.com.
The research is part of Mizzou Advantage, the five unique areas that set MU apart from other universities. The project contributes to the “Managing Innovation: Navigating Disruptive and Transformational Technologies” initiative that will touch on virtually every part of the university to explore areas in which existing technologies are changing rapidly
By RealAge: the Website of Mehmet Oz MD and Michael Roizen MD, September 12, 2011 — Good news for people who feel a hint of anxiety every time they forget where they put their keys. More than 50 percent of Alzheimer’s cases may be preventable.
In fact, research suggests that there are seven key lifestyle changes people could make to help protect themselves from the memory-stealing disease.
The Super 7
More research is needed to confirm whether there is a causal link between these seven key risk factors and Alzheimer’s. But there are plenty of other good health reasons to make the following changes:
- Get moving. Inactivity is linked to greater Alzheimer’s risk, so go for a walk every day. Walking every day can keep your brain from shrinking, too.
- Don’t smoke. Or quit if you do. Smoking may up the likelihood of Alzheimer’s.
- Eat more watermelon. Why? A compound in this juicy summer fruit can help lower your blood pressure by as much as nine points! And low blood pressure at middle age may help protect against Alzheimer’s.
- Go to bed. Getting a good night’s sleep can lower your risk of type 2 diabetes. And new research suggests that developing type 2 diabetes may up your chances of getting Alzheimer’s.
- Walk outside. People who exercise outside — versus at the gym or inside the home — have less depression. And that’s good news for the brain, because depression may up the risk of Alzheimer’s.
- Take a class. Higher education is linked to lower rates of Alzheimer’s.
- Drop a few. Becoming obese at middle age may be connected to higher Alzheimer’s risk.