The first major overhaul in more than 25 years of diagnostic criteria for Alzheimer’s disease has resulted in a new, broader definition of Alzheimer’s that includes the disease’s mild and presymptomatic stages – yet it will be years before clinicians will be able to treat the disease in these early stages, authors of the new criteria say.
The criteria, developed through a joint workshops supported by the Alzheimer’s Association and the National Institutes of Health/National Institute on Aging, were published in four articles – collectively, the National Institute on Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s Disease – appearing online April 19 in the journal Alzheimer’s & Dementia (doi:10.1016/j.jalz.2011.03.008.)
The criteria divide the disease into three stages: preclinical Alzheimer’s, marked by no outward symptoms and only measurable changes in biomarkers such as spinal fluid chemistry; mild cognitive impairment, in which changes in memory and thinking appear but do not yet compromise everyday activities and functioning; and dementia, the defining trait of late-stage disease.
Currently, the criteria offer no way to diagnose Alzheimer’s in a preclinical state, as appropriate biomarkers are still being investigated and standardized, which means that "preclinical Alzheimer’s" remains mainly for future studies to define.
However, the publication of the new criteria makes it official that the middle stage, measurable mild cognitive impairment, can be considered part of the disease spectrum for Alzheimer’s. In other words, Alzheimer’s can now be defined by subtle brain changes rather than exclusively by dementia.
"The term we’re using is ‘MCI [mild cognitive impairment] due to Alzheimer’s disease,’ " said Marilyn Albert, Ph.D., of Johns Hopkins University, Baltimore, one of the papers’ lead authors, in an April 18 teleconference with the scientists who revised the criteria. Dr. Albert added that the term and the concept had been accepted in clinical practice for roughly a decade, if not formally defined.
In 1984, the last time comprehensive criteria for Alzheimer’s were published, "we thought of Alzheimer’s [primarily as] dementia," said Dr. Guy McKhann, also of Johns Hopkins, in the same teleconference. The biggest difference today, he said, "is that we now think of this process as a continuum" inclusive of MCI.
The authors cautioned that more work is needed to distinguish people with MCI who will go on to develop Alzheimer’s dementia from those who will not. Biomarkers such as beta-amyloid, they said, will likely play an important role in identifying these patients, whom the authors estimate to exist in numbers at least equal to the number of patients with current dementia.
The importance of viewing Alzheimer’s as a continuum or spectrum – making the early stages of Alzheimer’s officially Alzheimer’s – is that it aids research, particularly drug development, Dr. McKhann said, adding that there is little point in "looking for new medicines if you’re only going to try them in people with advanced dementia."
While there are currently no established clinical protocols for treating people with MCI, Dr. Reisa A. Sperling of Brigham and Women’s Hospital and Harvard Medical School, Boston, said in the teleconference that clinicians had the option of referring to research settings when possible. "There are ongoing clinical trials of drugs in people with MCI due to Alzheimer’s," Dr. Sperling said.
With regard to potential conflicts of interest, Dr. Albert serves as a consultant to Genentech and Eli Lilly and receives grants to her institution from GE Healthcare. Dr. McKhann serves on a Data Safety Monitoring Board for Merck; Dr. Sperling has served as a site investigator and/or consultant to several companies developing imaging biomarkers and pharmacologic treatments for early AD, including Avid, Bayer, Bristol-Myers Squibb, Elan, Eisai, Janssen, Pfizer, and Wyeth.