Miami Herald (FL)
April 28--Mary had worked as a nursing executive in South Florida for more than three decades when she noticed her first memory lapses. She would forget when reports were due, when staff was scheduled to meet, what her employees had told her in the hallway. To compensate, she worked longer hours.
Eventually, when her extra efforts didn't work, she went to see Dr. Ranjan Duara, medical director of the Wein Center for Alzheimer's Disease and Memory Disorders at Mount Sinai Medical Center in Miami Beach. After a battery of tests, including an MRI, she received the diagnosis she feared: Alzheimer's disease.
And she hadn't even turned 60.
"I was devastated," she recalls. "I knew what it meant." She had tended to her father for years after he was diagnosed with AD.
Mary, who asked that her real name not be used, is 61 now and has been retired for about a year. The initial shock has worn off, replaced by a desire and determination to travel and enjoy her family as long as possible.
She's grateful that early detection of the devastating disease has helped her better plan for the future.
"In a way," she says, with a rueful laugh, "it's a blessing to know what you have."
For people like Mary, relatively new tests -- and those currently in the research pipeline -- are helpful tools that allow for earlier detection of this disease, a necessary and important step in developing a treatment plan to slow its progress. Traditionally, the only way families got confirmation of Alzheimer's was after the fact: an autopsy revealed the plaques and tangles in the brain characteristic of the disease. Doctors arrived at a diagnosis after ruling out other explanations for the memory loss and through extensive cognitive testing.
But those telltale plaques and tangles so common in Alzheimer's can start 10 to 20 years before any symptoms appear. Researchers have long sought a way of detecting those signature markers long before a patient's memory loss is so severe they can't function. This is particularly important because as the U.S. population ages, more and more people are expected to be diagnosed with the disease.
More than five million Americans are currently living with Alzheimer's, according to the Alzheimer's Association, and experts predict that as many as 16 million will have it by 2050. Nearly one in three seniors who die each year has some form of dementia, including Alzheimer's. In fact, Alzheimer's is the sixth-leading cause of death overall and the fifth for those 65 and older.
Caring for those with the disease is also costly -- an estimated $203 billion this year alone. The toll, however, can be measured in more than dollars. The Alzheimer's Association estimates that 15.4 million relatives and friends provided 17.5 billion hours of unpaid care valued at $216 billion in 2012, an equation that only begins to define the demands placed on the families of Alzheimer's patients.
Though Alzheimer's is the only top 10 cause of death that has no prevention or cure, doctors say early detection tests can alleviate some of the inevitable stress that accompanies not having a diagnosis, or an incomplete one.
Specialists go through a medical workout to determine what is causing a patient's memory loss. Initial steps include a variety of tests to determine the extent of that loss and general health, including medical history and figuring out if any family member has been diagnosed with Alzheimer's or another form of dementia.
Standard tests also include measuring reflexes, balance, vision and hearing. Blood and urine tests may be ordered to rule out other possible causes of cognitive problems. In addition, patients undergo two to six hours of specific standardized testing that can measure the ability to solve simple problems as well as short-term and long-term memory.
"You need a full history to rule out medical and psychiatric conditions that affect memory," says Dr. Elizabeth Crocco, chief of the division of geriatric psychiatry inpatient unit at Jackson Memorial Hospital. These include depression, bipolar disease or schizophrenia. Even anemia, vitamin deficiencies and too much medication can affect memory.
If these tests point to cognitive impairment, an MRI of the brain is usually ordered for the patient, says Dr. Clinton Wright, an associate professor of neurology and the scientific director for the Evelyn F. McKnight Institute at the University of Miami. Magnetic resonance imaging or Computed Tomography (CT), another kind of brain imaging scan, can further rule out other causes that may cause symptoms similar to Alzheimer's, including tumors, strokes, head trauma or building of fluid in the brain.
These tests do more than that, however. They also can provide information on the shape, position or volume of brain tissue -- an important piece of the medical puzzle, because the brains of people with Alzheimer's are different than those of healthy people. For example, as the disease progresses, the brain and part of the hippocampus shrinks as nerve cells and their connections die.
"We can be confident [in our diagnosis] about people with a memory disorder in combination with the tests," says Wright, "but if someone is only worried about their memory and is not impaired we have very little certainty."
Other tests available or in the research phase include:
A spinal fluid test, obtained through a spinal tap, identifies beta amyloid, a protein fragment that forms plaques in the brain; tau, a protein that accumulates when nerve cells and their connections are damaged; and phosphorylated tau, a protein marker of neurofibrillary tangle burden --one of the hallmarks of Alzheimer's disease -- in the brain. The presence of these markers provides a very accurate indication of Alzheimer's. (On the other hand, if only amyloid is detected without tau doctors can only say that a patient is "at risk" of getting Alzheimer's.)
Duara of the Wein Center says spinal taps in potential Alzheimer's cases are rarely used in the United States but are quite common in other countries. "Here they are not popular because they are considered invasive, costly and time-consuming. It's not routine," he says.
The spinal fluid test is covered by Medicare and some private insurance carriers, but should only be done as part of a comprehensive medical exam that includes a full clinical evaluation.
PET scans can also test for various amyloid deposition as markers of Alzheimer's. The FDA recently approved a radioactive tracer than can quantify the amount of amyloid in the brain. Patients with deposits of beta amyloid seen on these PET scans and dementia are more likely to have Alzheimer's, but there is still intense debate (and research) about how PET evidence of amyloid brain deposits can predict who is going to get the disease.
A different type of PET scan can also measure how much glucose is being used by the brain. (The more active the brain, the more glucose it uses.) So far no PET scan has been developed to measure tau, the protein that, along with beta amyloid, is the signature of Alzheimer's.
PET scans are used in distinguishing Alzheimer's from other dementias when the diagnosis is in question, but because of their high cost, insurance will not cover them in the diagnosis of Alzheimer's.
Blood tests, as well as urine tests, are being researched around the world in hopes that one day they will accurately measure the bio-markers of the disease. All are in the experimental stage. "The dream is that we will one day have blood tests that detect the markers in the same way we have tests for high cholesterol that tell us a patient is at risk of heart disease," Duara says.
Though years away, that dream may be getting closer. In March, researchers at the University of Nottingham told an Alzheimer's conference in the United Kingdom that they are a decade from developing a test that can detect the bio-markers found in the disease, including amyloid and APOE, a gene that can increase an individual's risk of developing late-onset Alzheimer's.
An eye test being developed by Cognoptix is halfway through clinical trials. The SAPPHIRE II is designed to detect a specific fluorescent signature of ligand-marked beta amyloid in the lens of the eye.
Genetic tests are available to indicate increased risk for Alzheimer's, but there are only a few rare genes that cause the disease directly. "It's something that can be used as a risk factor but not a diagnostic test," says UM's Wright.
For family caregivers of Alzheimer's patients, tests that provide them with an early diagnosis are a blessing in disguise.
Judy, a Coral Springs caregiver, has been caring for her 86-year-old mother since she was diagnosed with Alzheimer's through clinical evaluation and an MRI. The diagnosis helped the family put her financial and legal papers in order. It did much more, too.
"When you get that early diagnosis, it helps you understand what is going on day to day," Judy says. "When they do things that are off the wall, you're prepared and you know it's part of the disease."
(c)2013 The Miami Herald
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