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Important Notice: The Alzheimer Research Forum does not
provide medical advice nor promote any product or service. The contents are for
informational purposes only and are not intended to substitute for professional
medical advice, diagnosis or treatment. Always seek advice from a qualified physician
or health care professional about any medical concern, and do not disregard professional
medical advice because of anything you may read on this web site. The views of individuals
quoted on this site are not necessarily those of the Alzheimer Research Forum.
Updated 27 October 2007
The standard medical workup for Alzheimer disease includes a medical history and
physical examination, as well as laboratory tests, radiology, and neuropsychological
testing (Geldmacher, D.S. and Whitehouse, P.J. 1997). These three test categories
are described below. In addition, there are nonstandard or investigational tests
that may be applied in individual cases.
Laboratory tests
There is currently no laboratory test that can diagnose Alzheimer disease with greater
accuracy than can be attained by a standard clinical examination. The laboratory
tests employed in a standard workup are intended to rule out other causes of dementia,
such as nutritional deficiencies, infection, metabolic disorders, drug effects,
and so forth. These may include:
- Urinalysis and microcopy
- Blood count to investigate anemia, infection
- Serum electrolytes levels to investigate metabolic disease
- Serum chemistry panel, including liver function tests
- Thyroid panel to rule out hypothyroidism
- Serum vitamin B12 to rule out deficiency
- Neurosyphilis serology
- Urine toxicology
- Serum toxicology (for alcohol, medications, drugs, etc.)
- ESR, screens for connective tissue disease
-
HIV titer
Radiology
Brain imaging (X-ray, CT, SPECT, PET, MRI) is not considered part of a standard
workup, but is often ordered by a physician to help rule out conditions such as
tumor, infarcts, hydrocephalus, etc. Although expensive and, to date, adding no
great treatment options, MRI is currently the radiological modality of choice. Magnetic
resonance imaging (MRI) can reveal brain tissue loss patterns characteristic of
later-stage Alzheimer's, and is seen as a useful adjunct to standard methods. MRI
can help to differentiate AD cases from other types of dementia, particularly frontal
lobe dementia.
Recent research indicates that high-resolution structure imaging (MRI) and functional
imaging (fMRI, PET) can detect changes that are predictive of Alzheimer's (Silverman
et al., 2001). These studies may lead to new diagnostic approaches for mild
cognitive impairment and early Alzheimer's in the next few years.
Neuropsychological tests
These tests enable a clinician to analyze a patient's cognitive status, as well
as emotional, psychological, motor, and sensory functions. They are performed for
the following reasons:
- Neuropsychological tests are required for a clinical diagnosis of Alzheimer's
- They are helpful for ruling out other types of dementia
- They enable a physician to document the progression of the disease
-
They can identify depression or suicidal ideation, which can be treated
There are many types of neuropsychological tests for dementia (see
Neuropsychological Tests). The one most commonly used in a standard medical
work up is the Mini-Mental State Exam (MMSE).
It is not strictly diagnostic of dementia, but is useful for assessing cognitive
status. It is also simple, fast and inexpensive.
Nonstandard or investigational tests
Most clinical experts are skeptical of the diagnostic tests that are being developed
for Alzheimer's. No biological marker for Alzheimer's has been shown yet to surpass
the sensitivity and specificity that is already available through a proper clinical
examination. However, the door remains open for new tests that may meet these criteria.
An important emerging area in diagnostic research are approaches for detecting very
early Alzheimer's, even before the onset of clinical symptoms. Such tests could
become widely deployed to screen elderly populations, if preventive therapies are
ever developed. Diagnostic test that are currently available but not included in
a standard workup, and those under development are described below:
Genetic tests
Three genes are known to cause rare, inherited forms of Alzheimer disease. The
test for the most common of these, presenilin-1, is commercially available from
Elan Pharmaceuticals and may be recommended for individuals with a clear family
pattern of Alzheimer's with an unusually early onset. A risk factor for late-onset
Alzheimer's is the E4 variant of the apolipoprotein E (ApoE) gene. In the past,
testing for ApoE genotype was not recommended for the purpose of predicting risk.
It is not clinically available for that purpose, only for helping secure a diagnosis.
That view may be modified as new research shows the usefulness of ApoE genetic testing
to counsel families with a history of AD, or to guide future treatment. For more
details, see our Webinar on
Susceptibility Testing and Risk Assessment in Alzheimer Disease. Additional
genetic tests may become available as new genetic risk factors are discovered.
For a current view on the ethics of genetic testing, see the American Geriatrics
Society Ethics Committee's Position Statement on Genetic Testing for Late-Onset Alzheimer's
Disease.
High-resolution MRI
MRI is currently used as a research tool to measure changes in the size of vulnerable
brain areas such as the entorhinal cortex and hippocampus. Individuals are followed
over time for reduction in the size of these areas. Research studies indicate that
tissue loss associated with very early AD can be detected by MRI, even before cognitive
symptoms have become observable (Juottonen, et al) and could become an important
tool in identifying individuals who can benefit from treatment to delay disease
progression. Such tests could become available at any large hospital with high-resolution
MRI capabilities.
Functional brain imaging (PET, fMRI)
Radiological tools that detect altered metabolism in specific brain regions may
become useful adjuncts in the differential diagnosis of AD (Silverman
et al., 2001). These tests can be expensive, invasive (for example requiring
injection of a chemical into the blood) and restricted to hospital that own the
costly equipment. Given current technology, these methods are most likely to prove
their value as research tools to develop surrogate markers that are more appropriate
for broad screening.
Electroencelphalogram (EEG)
Some physicians and researchers think that the EEG is a good tool to use in dementia
diagnostics, particularly when a patient presents with unusual findings.However,
many neurologists feel that the overlap is too great between normal and Alzheimer's
disease patient findings. The EEG pattern supporting possible AD diagnosis is normal/nonspecific
changes, for example, increased slow-wave activity. (Rosen,
1997).
Cerebrospinal fluid (CSF) tests
These are highly invasive and not generally recommended for a diagnostic screen.
Tests for various proteins that have been associated with Alzheimer pathology, including
tau, amyloid beta peptide and AD7C-NTP are being developed by companies.
Blood tests
With the exception of genetic tests, tests that involve analysis of blood samples
are only in experimental stages. Assays of iron binding protein p97 (Kennard ML,
et al 1996) have shown some impressive preliminary results (not commercially available).
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