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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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