For the first time in 27 years, clinical diagnostic criteria for
Alzheimer’s disease dementia have been revised, and research
guidelines for earlier stages of the disease have been
characterized to reflect a deeper understanding of the disorder.
The National Institute on Aging/Alzheimer’s Association Diagnostic
Guidelines for Alzheimer’s Disease outline some new approaches for
clinicians and provides scientists with more advanced guidelines
for moving forward with research on diagnosis and treatments. They
mark a major change in how experts think about and study
Alzheimer’s disease. Development of the new guidelines was led by
the National Institutes of Health and the Alzheimer’s
Association.
The original criteria were the first to address the disease and
described only later stages, when symptoms of dementia are already
evident. The updated guidelines announced today cover the full
spectrum of the disease as it gradually changes over many years.
They describe the earliest preclinical stages of the disease, mild
cognitive impairment, and dementia due to Alzheimer’s pathology.
Importantly, the guidelines now address the use of imaging and
biomarkers in blood and spinal fluid that may help determine
whether changes in the brain and those in body fluids are due to
Alzheimer’s disease. Biomarkers are increasingly employed in the
research setting to detect onset of the disease and to track
progression, but cannot yet be used routinely in clinical diagnosis
without further testing and validation.
“Alzheimer’s research has greatly evolved over the past quarter
of a century. Bringing the diagnostic guidelines up to speed with
those advances is both a necessary and rewarding effort that will
benefit patients and accelerate the pace of research,” said
National Institute on Aging Director Richard J. Hodes, M.D.
“We believe that the publication of these articles is a major
milestone for the field,” said William Thies, Ph.D., chief medical
and scientific officer at the Alzheimer’s Association. “Our vision
is that this process will result in improved diagnosis and
treatment of Alzheimer’s, and will drive research that ultimately
will enable us to detect and treat the disease earlier and more
effectively. This would allow more people to live full, rich lives
without—or with a minimum of—Alzheimer’s symptoms.”
The new guidelines appear online April 19, 2011 in
Alzheimer’s & Dementia: The Journal of the Alzheimer’s
Association. They were developed by expert panels convened last
year by the National Institute on Aging (NIA), part of the NIH, and
the Alzheimer’s Association. Preliminary recommendations were
announced at the Association’s International Conference on
Alzheimer’s Disease in July 2010, followed by a comment period.
Guy M. McKhann, M.D., Johns Hopkins University School of
Medicine, Baltimore, and David S. Knopman, M.D., Mayo Clinic,
Rochester, Minn., co-chaired the panel that revised the 1984
clinical Alzheimer’s dementia criteria. Marilyn Albert, Ph.D.,
Johns Hopkins University School of Medicine, headed the panel
refining the MCI criteria. Reisa A. Sperling, M.D, Brigham and
Women’s Hospital, Harvard Medical School, Boston, led the panel
tasked with defining the preclinical stage. The journal also
includes a paper by Clifford Jack, M.D., Mayo Clinic, Rochester,
Minn., as senior author, on the need for and concept behind the new
guidelines.
The original 1984 clinical criteria for Alzheimer’s disease,
reflecting the limited knowledge of the day, defined Alzheimer’s as
having a single stage, dementia, and based diagnosis solely on
clinical symptoms. It assumed that people free of dementia symptoms
were disease-free. Diagnosis was confirmed only at autopsy, when
the hallmarks of the disease, abnormal amounts of amyloid proteins
forming plaques and tau proteins forming tangles, were found in the
brain.
Since then, research has determined that Alzheimer’s may cause
changes in the brain a decade or more before symptoms appear and
that symptoms do not always directly relate to abnormal changes in
the brain caused by Alzheimer’s. For example, some older people are
found to have abnormal levels of amyloid plaques in the brain at
autopsy yet never showed signs of dementia during life. It also
appears that amyloid deposits begin early in the disease process
but that tangle formation and loss of neurons occur later and may
accelerate just before clinical symptoms appear.
To reflect what has been learned, the National Institute on
Aging/Alzheimer’s Association Diagnostic Guidelines for Alzheimer’s
Disease cover three distinct stages of Alzheimer’s disease:
- Preclinical The preclinical stage, for which the guidelines
only apply in a research setting, describes a phase in which brain
changes, including amyloid buildup and other early nerve cell
changes, may already be in process. At this point, significant
clinical symptoms are not yet evident. In some people, amyloid
buildup can be detected with positron emission tomography (PET)
scans and cerebrospinal fluid (CSF) analysis, but it is unknown
what the risk for progression to Alzheimer’s dementia is for these
individuals. However, use of these imaging and biomarker tests at
this stage are recommended only for research. These biomarkers are
still being developed and standardized and are not ready for use by
clinicians in general practice. - Mild Cognitive Impairment (MCI) The guidelines for the MCI
stage are also largely for research, although they clarify existing
guidelines for MCI for use in a clinical setting. The MCI stage is
marked by symptoms of memory problems, enough to be noticed and
measured, but not compromising a person’s independence. People with
MCI may or may not progress to Alzheimer’s dementia. Researchers
will particularly focus on standardizing biomarkers for amyloid and
for other possible signs of injury to the brain. Currently,
biomarkers include elevated levels of tau or decreased levels of
beta-amyloid in the CSF, reduced glucose uptake in the brain as
determined by PET, and atrophy of certain areas of the brain as
seen with structural magnetic resonance imaging (MRI). These tests
will be used primarily by researchers, but may be applied in
specialized clinical settings to supplement standard clinical tests
to help determine possible causes of MCI symptoms. - Alzheimer’s Dementia These criteria apply to the final stage of
the disease, and are most relevant for doctors and patients. They
outline ways clinicians should approach evaluating causes and
progression of cognitive decline. The guidelines also expand the
concept of Alzheimer’s dementia beyond memory loss as its most
central characteristic. A decline in other aspects of cognition,
such as word-finding, vision/spatial issues, and impaired reasoning
or judgment may be the first symptom to be noticed. At this stage,
biomarker test results may be used in some cases to increase or
decrease the level of certainty about a diagnosis of Alzheimer’s
dementia and to distinguish Alzheimer’s dementia from other
dementias, even as the validity of such tests is still under study
for application and value in everyday clinical practice.
The panels purposefully left the guidelines flexible to allow
for changes that could come from emerging technologies and advances
in understanding of biomarkers and the disease process itself.
“The guidelines discuss biomarkers currently known, and mention
others that may have future applications,” said Creighton H.
Phelps, Ph.D., of the NIA Alzheimer’s Disease Centers Program.
“With researchers worldwide striving to develop, validate and
standardize the application of biomarkers at every stage of
Alzheimer’s disease, we devised a framework flexible enough to
incorporate new findings.”
