More than 27 years ago, the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s and Related Disorders Association (now the Alzheimer’s Association) released diagnostic criteria for Alzheimer’s disease (AD). At the time, AD was thought of only as a dementia. The 1984 criteria stated that the ultimate AD diagnosis was dependent on pathology. Since that time, the basic concepts of AD have changed significantly, and researchers have uncovered important clues on the diagnosis of AD and dementia.

Updating Diagnostic Criteria for Alzheimer’s

The National Institute of Aging of the NIH and the Alzheimer’s Association recently called a meeting to discuss whether or not the diagnostic criteria required updating. Three subgroups were established to discuss the
criteria, based on what would be the biggest changes in the concepts of AD (Table 1). These included that AD starts years and perhaps decades before dementia develops and symptoms are visible. The result of this collaboration was the establishment of new guidelines based on four articles collectively called the “National Institute on Aging/ Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease.” The document was published in the April 22, 2011 online edition of Alzheimer’s & Dementia.

“The field is changing rapidly, and the hope is biomarkers will become more widely available and used in diagnoses.”

“The pre-symptomatic phase of AD includes people who have laboratory evidence of the disease but no symptoms,” explains Guy M. McKhann, MD, who was a member of the group that updated the diagnostic criteria. “The minimal cognitive impairment (MCI) phase includes people with memory problems who haven’t reached the stage of being demented. The final phase includes those who have dementia due to AD.” Defining AD as a spectrum that starts with early changes in the brain will help facilitate clinicians’ ability to treat presymptomatic AD in the future, according to the guideline authors. It is during the asymptomatic phase that detrimental changes occur in the brain. Individuals with evidence of these changes upon testing for biomarker presence are at increased risk for cognitive and behavioral impairment, as well as progression to AD. “The use of these biomarkers in diagnosing Alzheimer’s dementia and MCI also appeared over the last 27 years,” notes Dr. McKhann.

Several biomarker types have emerged since the last criteria were released (Table 2). “Some biomarkers are related to imaging, including those that show evidence of structural change in the brain and accumulation of components of the amyloid plaque—the breakdown product that helps form AD,” says Dr. McKhann. He feels that one of the biggest breakthroughs in AD research in the past decade has been the ability to image amyloid in the brain with PET scans. “The other types of biomarkers look for the presence of tau or amyloid breakdown products in spinal fluid.”

There was a broad consensus among the workgroups that additional research is needed to validate the application of biomarkers in diagnosing AD. The guidelines propose using biomarkers in AD and MCI due to AD as a research agenda only, not as a current application in clinical settings. “While these biomarkers have been relatively well established when utilized properly in first-rate labs, they’re not ready for general use because of standardization issues,” adds Dr. McKhann. “The field is changing rapidly, and the hope is biomarkers will become more widely available and used in diagnoses. With these advancements, the criteria will likely need updating.”

Making an Alzheimer’s Diagnosis

The most recent guidelines pay more attention to the differential diagnosis of AD, according to McKhann. “When deciphering AD from vascular disease of the brain or other neurodegenerative diseases, clinicians should keep in mind that AD is an age-dependent process. The proportion of 65-year-olds who have AD is probably less than 10%, but it’s probably 35% to 40% among 90-year-olds.”

A proportion of those who have AD also have other neurological problems that can make diagnoses challenging. As such, Dr. McKhann stresses that providers become aware of these criteria and refer patients on to AD specialists in order to ascertain a firmer grip on the diagnosis. “The new criteria capitalize on the latest scientific knowledge and technological advances,” Dr. McKhann says, “allowing for improved diagnosis and earlier detection and treatment of AD. If you wait until full-blown dementia develops, it’s too late.”

Guy M. McKhann, MD, has indicated to Physician’s Weekly that he serves on a data safety monitoring board for Merck; has worked as a consultant for the Dana Foundation and Merck; and has received grants or research aid from the Dana Foundation, NIH, and NINDS.