New diagnostic criteria and guidelines for Alzheimer’s disease published for first time in 27 years

New criteria and guidelines for the diagnosis of Alzheimer’s disease have been published — for the first time in 27 years — by three expert workgroups spearheaded by the Alzheimer’s Association and the National Institute on Aging (NIA) of the National Institutes of Health (NIH).

The workgroups published four articles including ready-to-use clinical diagnostic criteria for Alzheimer’s disease dementia and mild cognitive impairment (MCI) due to Alzheimer’s. A research agenda was proposed for preclinical Alzheimer’s. The use of biomarkers in Alzheimer’s dementia and MCI due to Alzheimer’s was also proposed as a research agenda only, and is not intended for application in clinical settings at this time.

The articles — collectively, the National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease — expand the definition of Alzheimer’s to include two new phases of the disease: (1) presymptomatic and (2) mildly symptomatic but pre-dementia, along with (3) dementia caused by Alzheimer’s. This reflects current thinking that Alzheimer’s begins creating distinct and measurable changes in the brains of affected people years, perhaps decades, before memory and thinking symptoms are noticeable.

“It is our hope that incorporating scientific knowledge gained and technological advances made over the past quarter century will improve current diagnosis, bring the field closer to earlier detection and treatment and, ultimately, lead to effective disease-modifying therapies,” said William Thies, Ph.D., Alzheimer’s Association chief medical and scientific officer. “Development and publication of these articles is a major landmark in the field. That said, publication of these articles is not yet the end of the process of developing new diagnostic criteria for Alzheimer’s, but is another major step in the process.”

“The new guidelines reflect today’s understanding of how key changes in the brain lead to Alzheimer’s disease pathology and how they relate to the clinical signs of mild cognitive impairment and Alzheimer’s disease dementia,” said Creighton Phelps, Ph.D., program director of the Alzheimer’s Disease Centers Program at the National Institutes of Health. “We are also beginning to be able to detect these changes at a preclinical stage, long before symptoms appear in many people. With further research on biomarkers, as set forth in the new guidelines, we may ultimately be able to predict who is at risk for development of mild cognitive impairment and Alzheimer’s dementia, and who would benefit most as interventions are developed.”

http://www.alz.org/news_and_events_diagnostic_criteria.asp

For the first time in 27 years, the definition of Alzheimer’s disease is being recast in new medical guidelines that reflect fast-mounting evidence that it begins ravaging the brain years before the symptoms of dementia.

The guidelines, to be issued Tuesday by the National Institute on Aging and the Alzheimer’s Association, divide the disease into three stages: a phase when dementia has developed, a middle phase in which mild problems emerge but daily functions can still be performed, and the most recently discovered phase, in which no symptoms are evident but changes are brewing in the brain.

“We’re redefining Alzheimer’s disease and looking at this in a different way than had ever been done,” said Creighton Phelps, director of the National Institute on Aging’s Alzheimer’s Disease Centers Program. “I think we’re going to start to identify it earlier and earlier.”

The drive to diagnose Alzheimer’s before it has progressed into profound dementia is also reflected in a bill introduced in Congress this month, which would create specific Medicare cost codes for Alzheimer’s diagnosis, including steps involving discussions between the patient’s doctor and caregivers, a recognition that keeping family members well-informed can result in better planning and care.

“Early diagnosis is really the key to this,” said Representative Edward J. Markey, Democrat of Massachusetts and a sponsor of the bill. “Oftentimes family members notice the symptoms in their loved ones, but it’s only years later that they get diagnosed or understand what resources are available.”

The most striking addition to the guidelines concerns methods that assess brain changes involved in Alzheimer’s, including brain scans and tests of cerebral spinal fluid. Such methods measure what are called biomarkers, physiological indicators that someone is likely to develop dementia eventually, just as cholesterol and blood pressure are biomarkers of impending heart disease.

For now, the guidelines specify that Alzheimer’s biomarkers — including abnormal levels of the proteins amyloid and tau, and shrinkage of certain brain areas — should not yet be put into widespread use, but used only with patients enrolled in clinical trials.

That is because scientists cannot yet standardize the results of the tests, or know “what measure is truly abnormal and what measure is not,” said Marilyn Albert, director of the Johns Hopkins Alzheimer’s Disease Research Center, and a leader of one working group that developed the new guidelines.

As many as a third of people with amyloid plaques in their brains, for example, have not developed Alzheimer’s symptoms by the time they die. The guidelines also urge caution because there is currently no drug known to halt or significantly delay the onset of symptoms, so people told they are likely to get Alzheimer’s have no effective medication to take.

“We don’t have enough information about what to tell people,” said Dr. Steven DeKosky, dean of the University of Virginia medical school, who participated in one of the working groups. “Until you can tell a clinician, ‘If you do this test you have X amount of reliability and to do that will make a difference in the life of your patient’ — until then, it remains in the lab.”

But the guidelines reflect a sense in the medical community that the moment when science will have more specific knowledge about biomarkers is not that far off. They are intended to encourage more research so that drugs can be developed to attack early brain changes and to identify people who might benefit from such drugs when they become available.

The goal, said William Thies, chief medical and scientific officer for the Alzheimer’s Association, is “extending the range of our ability to investigate this disease and eventually find the treatment that is going to be so necessary to avoid the epidemic of Alzheimer’s disease that we see facing us over the next 40 years.”

In the short term, the biggest impact is likely to be seen with people who fall into the middle phase, those with mild cognitive impairment linked to Alzheimer’s. Experts say there are at least as many people experiencing this phase as the 5.4 million people estimated to have Alzheimer’s dementia. And they expect others to now ask their doctors if they are showing signs of mild impairment, which include experiencing some difficulty or inefficiency with memory, attention or other mental faculties, while still being able to function independently.

Dr. Albert said that if patients with symptoms of mild cognitive impairment wanted to “increase the certainty” of the diagnosis by getting a brain scan or spinal fluid test, they should obtain such tests in a research trial so they have a better chance of getting accurate results.

The guidelines also clarify diagnosis criteria for people with dementia symptoms, distinguishing Alzheimer’s from other dementias, including vascular, fronto-temporal and Lewy body. And they note that the earliest symptom of Alzheimer’s dementia is not always memory loss, but could be mood changes or problems with language, spatial perception or reasoning.

Dr. Pierre Tariot, director of the Banner Alzheimer’s Institute in Phoenix, who was not involved in drafting the guidelines, called them “a step in the right direction” that he hoped would not be “misconstrued” as a sign that biomarker tests are further along than they are. He added, “The notion that Alzheimer’s disease is a continuum that has an extensive pre-symptomatic phase is a very important message to get out.”

Dr. Phelps said it would hardly be the last word from the medical community on Alzheimer’s.

“We’re not drawing a line and saying this is it,” Dr. Phelps said. “What we’re saying is this is the best of our knowledge and we’re not going to wait 27 years to revisit these again.”

http://www.nytimes.com/2011/04/19/health/19alzheimer.html?_r=1

ALZHEIMER’S DEMENTIA

Symptoms begin gradually, progressing over months or years.

Has at least two symptoms of cognitive or behavioral impairment; memory impairment not necessary; could include problems with language, object or face recognition, reasoning abilities, personality changes.

Symptoms impede functioning at work or in daily activities.

Does not have other types of dementia, like vascular, fronto-temporal or Lewy body.

MILD COGNITIVE IMPAIRMENT FROM ALZHEIMER’S

A change in cognition that does not meet definition of dementia.

Lower performance in one or more cognitive areas — memory, language, attention, visual spatial skills — than is expected for the person’s age and educational background.

Can still function in daily activities, but may be less efficient or accurate.

Recommended for research use only for now: biomarkers, like brain scans or spinal fluid tests to measure levels of proteins like amyloid and tau, may help confirm that the person’s impairment is related to Alzheimer’s.

PRECLINICAL ALZHEIMER’S (BEFORE SYMPTOMS APPEAR)

Recommended for research use only for now: biomarkers, like brain scans or spinal fluid tests to measure levels of proteins like amyloid and tau, may help confirm that the person has early signs of Alzheimer’s, like abnormal levels of amyloid, nerve degeneration, high levels of tau protein or signs of brain shrinkage.

http://www.nytimes.com/2011/04/19/health/19boxalzheimers.html