Alzheimers Disease – What’s New?

In the book Alzheimer’s Disease: Caregivers Speak Out, by Pam Haisman, one family caregiver states, “I wish everyone understood Alzheimer’s disease is the most insidious, inconceivably destructive disease to both patient and caregivers.”

Dementia is a loss of intellectual function (thinking, remembering and reasoning) so severe that it interferes with an individual’s daily functioning, and eventually results in death. Alzheimer’s disease (AD) is the most common form of dementia. It is a progressive, degenerative disease that attacks the brain and results in impaired memory, thinking and behavior.

The disease was first described by Dr. Alois Alzheimer in 1906. Since it was identified, much research has been done and a deeper understanding has developed regarding changes in the brain and behavioral changes characterizing the disease. Men and women are affected almost equally, and known risk factors are age and family history. Though most people diagnosed with AD are older than age 65, the disease can occur in people in their 30s, 40s and 50s.

No Single Test
The Alzheimer’s Association says that early and careful evaluation is important because many conditions, including some that are treatable or reversible, can cause dementia. There is currently no single test to identify Alzheimer’s. A comprehensive evaluation to establish a diagnosis includes a complete health history, physical examination, neurological and mental status assessment, analysis of blood and urine, electrocardiogram and chest X-rays. A physician will want to note the patient’s behavior over time, to understand the person’s illness.

Dr. Mike Mullan, MD, PhD, MRCPsych, a professor at the University of South Florida and director of the Roskamp Institute, a research facility in Tampa, was among those researchers who first identified mutations in the B-amyloid precursor protein gene that causes early-onset AD. He stated that the amyloid plaques and tangles found in the brain that are linked to AD can only be observed during autopsy.

Warning Signs of Alzheimer’s Disease
Memory loss that affects job skills
Difficulty performing familiar tasks
Problems with language
Disorientation to time and place
Poor or decreased judgment
Problems with abstract thinking
Misplacing things
Changes in mood or behavior
Changes in personality
Loss of initiative
Source: http://www.alz.org/

Though age and family history have been identified as potential risk factors, scientists remain uncertain about what causes AD. Researchers are currently delving into the role genetics plays in its development but agree that it is likely caused by many factors.

Research Advances
Recent experimental diagnostic studies are focusing on imaging techniques. Magnetic resonance imaging (MRI) and positron emission tomography (PET) look to see if cognitive markers or telltale changes in mental abilities and personality can be linked to early biological changes in the brain.

Research shows that brain imaging and scanning techniques are getting closer to pinpointing brain abnormalities that might enable physicians to diagnose people with the disease before symptoms appear. PET scans have shown that the group carrying the Alzheimer’s disease gene APOE-4 had significantly lower function in specific areas of the brain, located above and behind the temples.

In their book, Keep Your Brain Young, Guy McKhann, MD, of Johns Hopkins University School of Medicine, Baltimore, and Marilyn Albert, PhD, Harvard Medical School, Cambridge, MA, say that, for most people, the answer is more complicated. The APOE-4 gene “has been identified as increasing the risk of developing Alzheimer’s disease, but not invariably causing it.” Carrying this gene, they say, increases the risk of AD about fourfold, while another form of the gene, APOE-2, actually decreases one’s risk.

In the journal Proceedings of the National Aca.demy of Sciences, University of California Los Angeles researchers published a study comparing PET scans that showed brain function of people at high risk for developing AD with scans showing that of people who were not at high risk. The study group without the Alzheimer’s gene showed decline only in an area located in the front of the brain that is consistent with normal aging, the researchers said.

Dr. Mullan stated that “with MRI, it’s possible to visualize areas of the brain that shrink as the disease progresses. However, frequently by the time this shrinkage appears on MRI, clinical changes are already apparent.” PET looks at the function of the brain, specifically measuring the glucose and oxygen usage by nerve cells, he said. In the early stages of AD, the memory and learning areas have reduced usage of glucose and oxygen.

Alzheimer’s Statistics
Approximately 4 million Americans have Alzheimer’s disease. In a recent national survey, 19 million Americans said they had a family member with Alzheimer’s disease, and 37 million said they knew someone with the disease.
Unless a cure or prevention is found, 14 million Americans will have the disease by the middle of this century.
One in 10 persons over 65 and nearly half of those over 85 have the disease.
The life expectancy from the onset of symptoms is an average of 8 years and as many as 20 years or more.
The disease costs at least $100 billion a year in this country. The long-term care most patients need is not covered by Medicare or most private insurers.
The average lifetime cost per Alzheimer patient is $174,000.
Source: http://www.alz.org/

PET has been used as an early marker of Alzheimer’s; however, these indicators are not limited to AD, as they are seen in other forms of dementia as well. He points out that scanning technologies are most effective when they are combined with solid clinical evaluation and psychological testing.

Treatment
The FDA approved galantamine (ReminylÃ?®, Janssen Pharmaceutica Products) last year for the treatment of symptoms of AD. Rivastig.mine (ExelonÃ?®, Novartis Pharmaceuticals) was ap.proved in 2000. Two other drugs currently available, donepezil (AriceptÃ?®, Eisai and Pfizer) and tacrine (CognexÃ?®, First Horizon Pharmaceutical), treat symptoms by improving cognitive function. Through autopsies, it was discovered that the neurotransmitter acetylcholine, which is involved with memory function, was reduced in the brains of those with AD. These four drugs elevate acetylcholine. Drs. McKhann and Albert state that although these medications treat the symptoms of AD, they do not alter the disease’s mechanism or its progression.

Currently, researchers continue to investigate anti-inflammatory drugs to reduce the inflammation that accompanies plaque formation. Some studies have indicated that ibuprofen and COX-2 inhibitors appear to reduce the risk of Alzheimer’s. The National Institute on Aging is currently investigating in the Alzheimer’s Disease Anti-Inflammatory Prevention Trial (ADAPT) whether two NSAIDS, naproxen and celecoxib (CelebrexÃ?®, Pfizer and Pharmacia & Upjohn), can delay or prevent the onset of AD in healthy people who have a parent or sibling with the disease. The study will last up to 7 years.

Studies also have shown a relationship between certain cholesterol-lowering medications (statins) and decreased occurrence of AD. Because cholesterol is found in the plaque associated with AD, research with statins is promising, according to Dr. Mullan. He said researchers have also discovered that statins have anti-inflammatory attributes that may contribute to prevention of inflammatory damage that occurs in the brains of AD patients.

Search for Answers
Evidence also points to estrogen possibly protecting the brain and reducing the risk of AD in women. Drs. McKhann and Albert suggest that their female patients take estrogen, unless they have a strong family history of breast cancer. However, they point out, there is still no definitive evidence showing that estrogen alters the course of AD once it starts.

The Alzheimer’s Association reports that researchers also have been looking for enzymes that might be central to the formation of beta amyloid, the tiny protein fragments that accumulate into the dense, insoluble plaques in the brains of people with Alzheimer’s.

In 1999, a study published in Nature reported on mouse models with a form of the protein that begins the accumulation process of the amy.loid plaques. Immunization of these models with a synthetic protein fragment called AN-1792 had significantly reduced existing plaques, and prevented further plaques from developing. This year, however, clinical trials were permanently stopped March 1 after 15 participants developed symptoms of brain inflammation.

Also on March 1, a coordinated mobilization of organizations seeking a cure for AD and restoration of state funding to programs helping families living with AD was the focus of an Alzheimer’s summit in Tallahassee, FL. The sum.mit, sponsored by Florida Speaker of the House-Designate Johnnie B. Byrd Jr. and Rep. Carole Green, urged the Florida state legislature to invest in research for AD, and address long-term care issues.

Sometimes, the biggest fear is not getting the disease, but rather watching someone you love develop it. According to the Alzheimer’s Association, more than four in 10 (42 percent) Amer.icans say that they currently know someone suffering from AD, and nearly one in five (18 percent) indicate that someone in their family has the disease. Current research aims to help save families from the emotional roller coaster of knowing and/or caring for someone they love with AD.

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