The clinical guidelines for diagnosing whether someone has Alzheimer's disease haven't been updated since 1984. For the past 27 years, a person had to show dramatic memory problems and in many cases “severe” cognitive decline before being diagnosed with Alzheimer's. In most cases, this diagnosis couldn't be confirmed until after death, when an autopsy would reveal a brain riddled with abnormal protein deposits called plaques and tangles. Now, new guidelines for Alzheimer's disease definition and diagnosis have been put together by three expert panels and appear in a series of publications in the April 19 issue of the Alzheimer's & Dementia journal.
The updated guidelines redefine the disease progression to include an early “preclinical” stage, a middle stage called “mild cognitive impairment (MCI) due to Alzheimer's disease,” and a final stage of dementia due to the Alzheimer's related changes in the brain. In particular, the guidelines have added new detection methods to define each stage and determine whether any clinical change in thinking or memory is specifically due to Alzheimer's.
The findings are not without controversy. While all agree that medical research stands to greatly benefit from new assessment criteria, some media outlets have shrugged their shoulders, suggesting that this is more about calls for increased funding than for an immediate impact on concerned families.
Under the new guidelines, clinical definitions of cognitive decline are combined with what is known about protein biomarkers and brain imaging technologies such as MRI and PET scans. These panels clarified the difference between the presence of biological changes in the brain (beta-amyloid and tau proteins, the hallmarks of plaques and tangles, respectively) and the appearance of changes in brain function or cognitive decline. “There have been tremendous advances in biomarker research which now allow us to detect evidence of early Alzheimer's disease pathology in the living brain, likely more than a decade before clinical dementia,” said Reisa A. Sperling, M.D., Director of the Center for Alzheimer Research and Treatment at Brigham and Women's Hospital, Harvard Medical School, who chaired the “preclinical” panel.
Since cognitive symptoms are believed to appear long after structural or biochemical changes, the panels reasoned that evidence of these chemical or structural changes could be accepted as an indication of Alzheimer's disease. “The Alzheimer's disease process is long and goes on for years before the symptoms become severe,” says Bradley T. Hyman, M.D., Ph.D., Professor in the Department of Neurology, Massachusetts General Hospital and Harvard Medical School, chair of the dementia panel and contributor to the two other panels. “We hope that by diagnosing this disease in early stages, we'll be able to develop disease-modifying treatments.”
One of the updates to the old guidelines is the definition of the middle stage, “MCI due to Alzheimer's disease.” Previously, MCI was not necessarily specific to Alzheimer's disease. MCI, on its own, is defined as a set of mild cognitive difficulties that can be caused by Alzheimer's and also by a number of other conditions, like stroke, problems with blood vessels in the brain, dementia associated with Parkinson's disease, depression, drug interactions, and others.
With the new guidelines, if someone has the clinical signs of MCI and is positive for characteristics of Alzheimer's such as abnormal beta-amyloid and tau protein biomarkers, then there's an increasing likelihood that this is the new classification “MCI due to Alzheimer's disease” rather than just “MCI.” If someone is negative for both biomarkers, then the MCI is unlikely to be due to Alzheimer's and the clinician can look for other causes that would be managed and treated differently.
Currently, there are no disease-modifying treatments for Alzheimer's disease. Existing medications serve only to address symptoms without affecting the underlying progression of the disease. Concerned patients or family members are presented with the dilemma of whether an earlier positive diagnosis of Alzheimer's disease might provide a benefit or cause them greater stress.
Although many of the technologies described in the new criteria are not widely available at this time and are largely limited to facilities actively involved in research, there may be some immediate benefits to clinicians and patients with access to the tools. “These new guidelines help to better define whether someone's initial difficulties with cognition are due to Alzheimer's disease versus another cause,” says David M. Holtzman, M.D., Professor and Chairman of the Department of Neurology at Washington University School of Medicine, and expert on the “MCI due to Alzheimer's disease” panel. Though many dementias remain untreatable, some causes such as tumors or abnormal pressure in the brain may be treatable. “In addition,” says Holtzman, “the guidelines allow for a standardized way to diagnose Alzheimer's disease at all stages of the illness. This will be particularly important as effective treatments are being developed to delay the onset or prevent the disease.”
The promise of early diagnosis may have benefits that are not, strictly speaking, biological. “Disease-modifying treatments are our holy grail, but we also have to focus on the idea that biological changes are not the only toll that Alzheimer's disease has on patients and families,” says Guy Eakin, Vice President of Scientific Affairs at the BrightFocus Foundation. “Even if we can't yet cure Alzheimer's, new technologies may give patients and families valuable time to prepare for life changes.” In addition, many caregivers must make career, legal and financial decisions, as they prepare to devote more and more time and resources to caring for someone with Alzheimer's disease. Says Eakin, “For some families, even a few extra months may make a world of difference—especially if those months position the patient to have a greater voice in these decisions.”
Co-authors Bradley T. Hyman, M.D., Ph.D., Massachusetts General Hospital and Harvard Medical School, David M. Holtzman, M.D., Washington University School of Medicine, Reisa A. Sperling, M.D., Brigham and Women's Hospital, Massachusetts General Hospital, and Harvard Medical School, and Kristine Yaffe, M.D., University of California, San Francisco, are grant recipients of by BrightFocus’ Alzheimer's Disease Research program. Co-authors Dennis Dickson, M.D., Mayo Clinic, Jacksonville, David M. Holtzman, M.D., Washington University School of Medicine, and William Jagust, M.D., University of California, Berkeley, serve as scientific advisors to BrightFocus.
For the full press releases from the National Institute on Aging/National Institutes of Health and Alzheimer's Association (who jointly convened the expert panels), and for copies of the original publications from the Alzheimer's & Dementia journal, please refer to the following websites:
National Institutes on Aging/National Institutes of Health:
View all news updates for Alzheimer's disease
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