"It's pretty well understood that the pathology of Alzheimer's disease begins in the brain several years, if not decades, before clinical manifestations," says James Mastrianni, MD, PhD, associate professor of neurology at the University of Chicago Medical Center. Photo by Ted Grudzinski / AMA

Proposed Alzheimer's criteria call for early physician intervention

Experts are working to develop guidelines that can be applied in a physician's office without using biomarkers or imaging.

By — Posted Aug. 9, 2010

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For the first time in more than 25 years, medical experts are updating the diagnostic guidelines for Alzheimer's disease in light of new advancements in the pathology and progression of the disorder.

Those changes are designed to help physicians better diagnose patients with cognitive impairment who might have gone untreated because their symptoms did not fit existing disease criteria. The proposal urges doctors to look for earlier signs of the disease before patients develop Alzheimer's disease dementia.

"The new guidelines are a framework for describing a disease that has a much greater breadth than might have been thought in 1984, and doctors should be aware of that," said William Thies, PhD, chief medical and scientific officer of the Alzheimer's Assn.

The revisions are particularly important to primary care physicians because they treat at least 80% of the nation's dementia patients, said Guy McKhann, MD, a neurologist at Johns Hopkins Medicine in Baltimore. He is chairing one of the work groups developing the guidelines.

Since 1984, when the Alzheimer's criteria were published, researchers have learned that the disease process can start more than a decade before symptoms appear. Scientists have identified genetic risks of Alzheimer's, and they now understand that dementia can be caused by conditions other than Alzheimer's, such as cerebrovascular disease and Lewy body disease.

In 2009, the Alzheimer's Assn. and the National Institute on Aging organized three work groups of experts to review advancements and determine if diagnostic procedures should be changed. On July 13, they released their recommendations during the annual Alzheimer's Assn. International Conference on Alzheimer's Disease.

The proposed guidelines:

  • Call for removing age restrictions for the onset of the disease.
  • Include updated criteria to distinguish Alzheimer's dementia from other forms of cognitive impairment.
  • Expand symptoms beyond memory impairment to difficulty expressing one's self with words, spatial cognition problems, and impaired reasoning or judgment.

Health professionals are being urged to offer feedback on the proposal through August. The work groups will use the comments to amend the criteria, which could be published in early 2011, said Creighton Phelps, PhD, director of the Alzheimer's Disease Centers Program at the National Institute on Aging.

Some specialists have lauded the proposed changes -- particularly the emphasis on early detection -- as key to more aggressively addressing the disease that affects about 5.3 million Americans. Others have raised concerns about identifying people who might develop the progressive brain disorder a decade or more before symptoms of the disease appear.

Gregory Jicha, MD, PhD, associate professor of neurology at the University of Kentucky College of Medicine, stressed that health professionals must be cautious when identifying people who probably will develop Alzheimer's. "Someone could develop the early [signs] of Alzheimer's disease, but we don't know if the [condition] can spontaneously regress or resolve."

Some physicians question the use of neuroimaging and other biomarkers to predict people's risk of developing Alzheimer's by identifying the presence of the amyloid protein or shrinking of the hippocampus in temporal lobes, among other things. The biomarkers are not yet recommended for use in early detection because the technology has not been validated for such use.

Dr. Jicha cautioned that experts do not know how soon a person will develop Alzheimer's if a biomarker indicates they are on the path to the disease. "That's important [information to know] when we're giving out a diagnosis of Alzheimer's disease," he said.

The work groups are trying to develop criteria that can be implemented in a physician's office without the use of biomarkers or imaging. The challenge, however, is making the criteria applicable to neurologists and researchers.

"We hope to revisit [the recommendations] every year or two." Phelps said.

He said that as biomarkers become validated for early detection of the disease, they might be added to the Alzheimer's criteria as diagnostic tools. "But there's a sense that it is going to take some time," he said.

Ultimately, the work groups envision a set of guidelines that can be applied in any setting. Biomarkers would supplement the criteria that can be used by specialists.

Diagnosing Alzheimer's

Alan Adelman, MD, a family and geriatric physician in Hershey, Pa., has been caring for dementia patients for about 25 years. One of the biggest obstacles is diagnosing patients who do not meet the existing definition of Alzheimer's disease dementia but have some form of cognitive impairment.

He said new stages of Alzheimer's detailed in the proposed criteria probably would help diagnose this group of people.

Under the proposed guidelines, the first stage would be preclinical Alzheimer's disease, which is defined as early cognitive decline before overt symptoms are present. Biomarkers and other clinical tools would identify patients in this category.

Mild cognitive impairment due to Alzheimer's would be the second phase and indicate cognitive changes before dementia.

The most advanced stage would be Alzheimer's disease dementia. Criteria for diagnosing this condition would include symptoms with a gradual onset over months to years and worsening of cognition. Patients would have cognitive deficits in either amnestic presentation, such as trouble recalling recently learned information, or nonamnestic presentations, including problems recalling words.

The guidelines issued in 1984 feature only one category: definite Alzheimer's disease. The criteria for this diagnosis include dementia established by clinical examination, deficits in at least two areas of cognition, and onset between age 40 and 90.

Dr. Adelman said the mild cognitive impairment stage would probably be the most useful to him, because biomarkers to determine preclinical Alzheimer's have not been validated.

Chicago neurologist James Mastrianni, MD, PhD, recommends that physicians not take mild cognitive impairment diagnoses lightly.

"When you make this diagnosis ... it's telling a person who might be functioning normally with mild memory problems" that they could develop Alzheimer's, said Dr. Mastrianni, associate professor of neurology at the University of Chicago Medical Center. He also is director of the university's Center for Comprehensive Care and Research on Memory Disorders.

Dr. Mastrianni informs patients diagnosed with mild cognitive impairment that they are at a higher risk of developing Alzheimer's but that the condition cannot be confirmed. He tells these patients he will follow them annually to see if their symptoms progress.

By 2050, an estimated 13.5 million Americans 65 and older will have Alzheimer's, according to a report released in May by the Alzheimer's Assn. About 5.1 million people in that age group have the disease now.

There are about 100 drug trials searching for ways to slow the advancement of Alzheimer's, said Phelps, of the National Institute on Aging.

Thies, of the Alzheimer's Assn., believes that surveying patients' cognitive function for early indicators of the disease someday will be as common as measuring blood pressure.

"That's the future we have to envision. In order to get to that future, we need a framework like the [proposed] guidelines," he said.

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Criteria for Alzheimer's disease dementia

For the first time in more than 25 years, medical experts are updating the diagnostic guidelines for Alzheimer's disease. Here are the proposed criteria:

  • Symptoms have a gradual onset over months to years.
  • Patients have a history of worsening of condition by report or observation.
  • Cognitive deficits occur in either amnestic presentation, such as impairment in learning, or in nonamnestic presentation, which includes deficits in word-finding or spatial cognition.

Source: Alzheimer's Assn. (link)

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Alzheimer's time line

A history of Alzheimer's disease developments in the 20th and 21st centuries:

1910: Alzheimer's disease named by German psychiatrist Dr. Emil Kraepelin for German physician Dr. Alois Alzheimer, who first noticed symptoms such as profound memory loss in a patient.

1968: The first validated measurement scale developed to assess cognitive and functional decline in older adults.

1976: Alzheimer's disease identified as most common cause of dementia and major public health challenge in an Archives of Neurology editorial by neurologist Robert Katzman, MD.

1984: A protein known as beta-amyloid recognized as a component of Alzheimer's brain plaques and a prime suspect in triggering nerve cell damage.

1987: The first gene associated with rare, inherited forms of Alzheimer's disease identified: the gene on chromosome 21.

1991: The Tau protein recognized as the main component of neurofibrillary tangles, one of the two pathological hallmarks of Alzheimer's.

1993: Researchers identified APOE-e4 as the first gene that raises the risk for Alzheimer's but does not ensure that a person who has it will develop the disease.

1993: The Food and Drug Administration approved tacrine (Cognex) as the first drug targeting memory and thinking symptoms associated with Alzheimer's. Four more drugs were approved in the next 10 years.

2003: The National Alzheimer's Disease Genetics Study began. Blood samples were collected from families with several members who developed Alzheimer's late in life to identify additional Alzheimer's risk genes.

2010: A database was launched of 4,000 patients who participated in 11 pharmaceutical industry-sponsored clinical trials of Alzheimer's treatments.

Source: Alzheimer's Assn. (link)

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External links

Alzheimer's Assn.'s recommendations to update diagnostic criteria (link)

National Institute on Aging's Alzheimer's Disease Education and Referral Center (link)

"Changing the Trajectory of Alzheimer's Disease," Alzheimer's Assn., May (link)

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