Expert international workgroups convened by the Alzheimer's Association and the National Institute on Aging (NIA), an agency of the U.S. National Institutes of Health (NIH), jointly issued four updated criteria and guidelines to diagnose Alzheimer's disease. These criteria refine and broaden previous widely used guidelines jointly issued by the Alzheimer's Association and the NIH in 1984.
By incorporating new scientific insights and technological advances, the new guidelines aim to improve current diagnosis, strengthen autopsy reporting of Alzheimer's brain changes, and establish a research agenda for future progress in earlier detection and even greater diagnostic accuracy.
Three of the new guidelines focus on three stages of Alzheimer's disease: (1) dementia due to Alzheimer's, (2) mild cognitive impairment (MCI) due to Alzheimer's, and (3) preclinical (presymptomatic) Alzheimer's. The fourth guideline updates criteria for documenting and reporting Alzheimer's-related changes observed during an autopsy.
Current and future recommended use of guidelines
Core clinical diagnostic criteria spelled out in the guidelines for Alzheimer's dementia and MCI due to Alzheimer's can be used now in general practice. The guidelines for assessing brain changes during an autopsy can also be used now.
The guidelines on preclinical Alzheimer's define this condition as a newly recognized stage of the disease. In a "preclinical" disease stage, key biological changes are under way in the body, but the disease has not yet caused any noticeable "clinical" symptoms. Current scientific evidence suggests that in preclinical Alzheimer's, brain changes caused by the disease may begin years — or even decades — before symptoms such as memory loss and confusion occur. The guidelines are not an immediate call for diagnosis of this preclinical stage and do not include specific diagnostic criteria. They rather propose a research agenda to identify biomarkers that may signal when these presymptomatic brain changes begin.
Biomarkers, such as those sought for Alzheimer's disease, are benchmarks in the body that can be reliably measured to indicate the presence or absence of a disease, or the likelihood of later developing a disease. For example, blood glucose levels are a biomarker for diabetes, and blood cholesterol levels are a biomarker for heart disease. The strongest biomarker candidates for Alzheimer's disease include brain imaging studies using magnetic resonance imaging (MRI) or positron emission tomography (PET), and proteins in cerebrospinal fluid (CSF).
Identification of the newly defined preclinical stage of Alzheimer's will gain importance if researchers succeed in developing treatments that can slow or stop the progression of Alzheimer's. Such treatments may be most effective if used as early as possible in the course of the illness.
The guidelines for MCI due to Alzheimer's and Alzheimer's dementia also include research proposals for future use of biomarkers to increase diagnostic accuracy and optimize treatment. The neuropathologic guidelines recommend use of biomarker data to complement autopsy findings to help advance understanding of how closely biomarkers correlate with underlying physical processes.
Guideline commentary and free access
Each workgroup initially issued proposed recommendations that were posted here for public comment. The final versions of the guidelines, revised to reflect input from the professional community at large, now appear as free-access papers in Alzheimer's & Dementia®: The Journal of the Alzheimer's Association.
To access the guidelines or related resources, please visit the links below.
National Institute on Aging (NIA) – Alzheimer's Association Diagnostic Guidelines Focusing on the Three Stages of Alzheimer's Disease:
- Introduction. Written by representative members from the three workgroups focusing on Alzheimer's stages, this introduction provides background on the initiative and summarizes key issues and perspectives.
Free-access paper: Clifford R. Jack Jr. et al. "Introduction to the recommendations from the National Institute on Aging – Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease." Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011;7(3):257 – 262.
Dementia due to Alzheimer's disease. In this stage, impairments in memory, thinking and behavior decrease a person's ability to function independently in everyday life. This guideline updates and clarifies clinical criteria to diagnose dementia from all causes and specifically from Alzheimer's disease. These criteria are sufficiently broad and flexible to be used now both by community practitioners without access to neuropsychological testing, specialized brain imaging, or CSF testing and by specialists engaged in research or clinical studies who have access to such tools. In the future, biomarker evidence may provide additional diagnostic certainty, but much more research is needed to identify the most accurate biomarkers and confirm their usefulness.
Free-access paper: Guy M. McKhann et al. "The diagnosis of dementia due to Alzheimer's disease: Recommendations from the National Institute on Aging – Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease." Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011;7(3):263 – 269.
Workgroup members: Proposed criteria for Alzheimer's disease dementia
Mild cognitive impairment (MCI) due to Alzheimer's disease. In this stage, mild changes in memory and thinking are noticeable and can be measured on mental status tests, but are not severe enough to disrupt a person's day-to-day life. This guideline details four levels of certainty for ruling out other causes of MCI and arriving at a diagnosis of MCI due to Alzheimer's. Only the first level of certainty, which relies on core clinical criteria similar to those used today, is currently recommended for widespread use in general clinical practice. More research is needed before the other three levels of uncertainty, which incorporate biomarkers, may be useful outside research settings.
Free-access paper: Marilyn S. Albert et al. "The diagnosis of mild cognitive impairment due to Alzheimer's disease: Recommendations from the National Institute on Aging – Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease." Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011;7(3):270 – 279.
Workgroup members: Proposed criteria for mild cognitive impairment due to Alzheimer's disease
Preclinical Alzheimer's disease. This is a newly defined stage of the disease reflecting current evidence that measureable biomarker changes in the brain may occur years before symptoms affecting memory, thinking or behavior can be detected by affected individuals or their physicians. While the guidelines identify these preclinical changes as an Alzheimer's stage, they do not establish diagnostic criteria that doctors can use now. Rather, they propose additional research to establish which biomarkers may best confirm that Alzheimer's-related changes are underway and how best to measure them.
Free-access paper: Reisa A. Sperling et al. "Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging – Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease." Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2011;7(3):280 – 292.
National Institute on Aging (NIA) – Alzheimer's Association Guideline on Neuropathologic Assessment of Alzheimer's During an Autopsy
Workgroup members: Proposed criteria for preclinical Alzheimer's disease
- Reisa Sperling, M.D., Brigham and Women's Hospital, Harvard Medical School (Chair)
- Paul Aisen, M.D., University of California, San Diego
- Laurel Beckett, Ph.D., University of California, Davis
- David Bennett, M.D., Rush University Medical Center, Chicago
- Suzanne Craft, Ph.D., VA Puget Sound Health Care System, Seattle
- Anne Fagan, Ph.D., Washington University, St. Louis
- Takeshi Iwatsubo, M.D. University of Tokyo, Tokyo, Japan
- CliffordJack, M.D., Mayo Clinic, Rochester
- Jeffrey Kaye, M.D., Oregon Health & Science University, Portland
- Thomas Montine, M.D., Ph.D., Harborview Medical Center, Seattle
- Denise Park, Ph.D., University of Texas, Dallas
- Eric Reiman, M.D., Banner Alzheimer's Institute, Phoenix
- Christopher Rowe, M.D., University of Melbourne, Melbourne, Australia
- Eric Siemers, M.D., Eli Lilly and Company, Indianapolis
- Yaakov Stern, Ph.D., Columbia University, Sergievsky Center, New York
- Kristine Yaffe, M.D., University of California, San Francisco
. These criteria provide guidance for documenting and reporting Alzheimer's-related brain changes observed during an autopsy. Key recommendations include ranking the severity of Alzheimer's pathology based on three hallmark changes; reporting these rankings as "Alzheimer's disease neuropathologic changes" whether or not the person was ever diagnosed with Alzheimer's during life, with a goal of understanding the full range of brain changes that may occur in people with or without Alzheimer's symptoms; and including assessment of Lewy bodies, vascular abnormalities and other brain changes that commonly coexist with Alzheimer's hallmarks.
Bradley T. Hyman et al. "National Institute on Aging – Alzheimer's Association guidelines on neuorpathologic assessment of Alzheimer's disease." Alzheimer's & Dementia: The Journal of the Alzheimer's Association 2012;8(1):1 – 13.
Workgroup members: Neuropathologic assessment of Alzheimer's
- Bradley T. Hyman, M.D., Ph.D., Harvard Medical School, Boston, Massachusetts, USA, Co-chair
- Thomas J. Montine, M.D., Ph.D., University of Washington School of Medicine, Seattle, Washington, USA, Co-Chair
- Creighton H. Phelps, Ph.D., National Institute on Aging, Bethesda, Maryland, USA
- Thomas G. Beach, M.D., Ph.D., Banner Sun Health Research Institute, Sun City, Arizona, USA
- Eileen H. Bigio, M.D., Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Nigel J. Cairns, Ph.D., Washington University School of Medicine, St. Louis, Missouri, USA
- Maria C. Carrillo, Ph.D., Alzheimer's Association, Chicago, Illinois, USA
- Dennis W. Dickson, M.D., Mayo Clinic, Jacksonville, Florida, USA
- Charles Duyckaerts, M.D., Ph.D., Hôpital de la Salpêtriére, Paris, France
- Matthew P. Frosch, M.D., Ph.D., Harvard Medical School, Boston, Massachusetts, USA
- Eliezer Masliah, M.D., School of Medicine, University of California at San Diego, San Diego, California, USA
- Suzanne S. Mirra, M.D., State University of New York Downstate Medical Center, Brooklyn, New York, USA
- Peter T. Nelson, M.D., Ph.D., University of Kentucky, Lexington, Kentucky, USA
- Julie A. Schneider, M.D., Rush University Medical Center, Chicago, Illinois, USA
- Dietmar Rudolf Thal, M.D., University of Ulm, Ulm, Germany
- Bill Thies, Ph.D., Alzheimer's Association, Chicago, Illinois, USA
- John Q. Trojanowski, M.D., Ph.D., University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA Harry V. Vinters, M.D., University of California at Los Angeles, Los Angeles, California, USA