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Neuroimaging for Dementia and Alzheimer's Disease
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- Data supports either CT or MRI under most circumstances at the time of initial dementia
assessment to identify rare pathologies such as neoplasms or subdural hematomas
- When specific clinical criteria are met, FDG-PET can be utilized to distinguish between
Alzheimer’s and Pick’s (fronto-temporal) disease
- Molecular imaging examinations that detect specific biological characteristics of Alzheimer’s
disease, currently used as research tools, will become clinically available in the future for
early detection of disease
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There
are an estimated 4.5 million people in the United States with
Alzheimer’s disease (AD) at this time, accounting for approximately
60-70% of all cases of dementia in the elderly. As the post World War
baby boom population ages, it is anticipated that the number of
Alzheimer’s patients will grow dramatically, increasing the burden on
both the public healthcare system as well as the caregivers of these
patients. Unfortunately, treatments available at this time for AD are
not effective at slowing disease progression. However, for the first
time, promising disease-modifying therapies for AD are in large-scale
clinical trials and it is likely that some will become available within
the next few years.
The only definitive diagnosis of
AD is the detection of amyloid plaques and neurofibrillary tangles at
autopsy. A clinical diagnosis based on the history, physical
examination, neuropsychological evaluation, and laboratory tests is
usually accurate in established cases, but is more challenging in
earlier, milder forms of the disease. The role of neuroimaging at
present is primarily to identify potentially treatable underlying
conditions that arise in patients with unusual presenting symptoms.
While AD is by far the most common form of dementia (Table 1), other
etiologies must be considered because prognosis and management
strategies will differ. Neuroimaging is often useful for this purpose,
for example, in differentiating vascular and fronto-temporal dementias
from AD. The role of neuroimaging in the next few years will likely
include the direct identification of early amyloid AD pathology with
positron emission tomography (PET) and the detailed characterization of
brain chemistry with magnetic resonance spectroscopy (MRS).
MRI and CT
By the time AD symptoms are clinically established, structural brain
shrinkage in excess of normal aging is often evident and readily
detectable with either CT or MRI. AD causes atrophy of the entire
brain, although some regions such as the hippocampus are specifically
affected by AD and can be assessed with quantitative volumetric methods
that are usually applied to MRI (Figure 1). Up to 5% of patients
presenting for initial evaluation for dementia harbor a clinically
significant structural lesion that is not identified by history or
examination. Most commonly, these lesions are infarcts but occasionally
neuroimaging can reveal a tumor or subdural hematoma requiring surgical
evaluation. CT is usually adequate as an initial examination to look
for these lesions.
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Figure 1.
Coronal image of the brain, showing hippocampi (arrows). Serial
imaging, which is not used in clinical practice, is necessary to
demonstrate preferential shrinkage of the hippocampus that is
characteristic of AD.
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Dementia on the basis of cerebrovascular disease may occur alone or in
combination with AD (“mixed” dementia) and is associated with white
matter abnormalities that are more evident with MRI. Vascular dementia
remains a clinical diagnosis. Minimal changes on MRI, including white
matter abnormality and mild brain atrophy are usually age-related and
may provoke unnecessary concern. Normal pressure hydrocephalus is a
very rare condition whose clinical symptoms include ataxia,
incontinence, and dementia; imaging typically shows ventricular
enlargement.
| Table 1. Relative frequencies of causes of dementia in elderly patients |
| Alzheimer’s Disease |
60-70% |
| Vascular dementia |
20% |
| Mixed etiology |
6% |
| Fronto-temporal dementia |
5-10% |
| Dementia with Lewy bodies |
25% |
| Normal pressure hydrocephalus |
1% |
| Depression |
1% |
| Tumor |
1% |
| Note: Patients may have more than one cause of dementia |
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Figure 2.
FDG PET images showing patterns of metabolic activity that are
characteristic of patients with Alzheimer’s disease, Pick’s disease
(fronto-temporal dementia) and elderly individuals with no dementia.
Red, high FDG uptake, Blue, low FDG uptake.
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FDG-PET Imaging
FDG-PET is useful for distinguishing between Alzheimer’s and
fronto-temporal (Pick’s) dementias and is now Medicare reimbursable for
this purpose. Before FDG-PET can be ordered, a scheduling worksheet
must be completed that documents the justification for and potential
benefit of FDG-PET for clinical management of the patient (Table 2).
FDG-PET images show the regional distribution of the rate of glucose
metabolism. Because active neurons have a very high metabolic rate, FDG
uptake is high in brains of healthy subjects, especially in the cortex.
In contrast, FDG uptake in AD is greatly diminished, especially in the
temporal and parietal regions of the brain. The characteristic pattern
of FDG uptake seen in Alzheimer’s patients is very different from that
seen in fronto-temporal dementia (Figure 2), allowing the differential
diagnoses of these diseases.
| Table 2. Requirements for Ordering FDG-PET for Dementia Patients |
| At least 6 months of progressive dementia |
| Completed comprehensive neurological examination conducted by physician experienced in diagnosis and assessment of dementia |
| Meet diagnostic criteria for Alzheimer’s disease and fronto-temporal dementia |
| No clinical diagnosis for dementia symptoms |
| No previous brain SPECT or FDG PET for same indication |
Future Imaging Examinations for Dementia
Proton magnetic resonance spectroscopic imaging (MRS) can be performed
as an add-on examination after conventional MRI. Proton MRS imaging
assesses several characteristic hydrogen-containing biochemicals in an
array of voxels, each about 2-7 cm3,
which are displayed as a spectrum for each voxel of tissue. One of the
principle peaks in the spectrum of a healthy brain is that of the
neuronal marker, n-acetyl aspartate (NAA), while other major peaks
include choline, creatinine, and myo-inositol. Even before the
development of overt dementia due to AD, there is a decrease in the
ratio of NAA: creatinine in the temporal lobe, which is not seen in
patients whose memory loss and cognitive declines were attributed to
other causes of dementia.
Several highly specific PET
imaging agents have been developed which bind to the characteristic
ß-amyloid plaque found in AD. Currently, the most sensitive and
specific of these, known as Pittsburgh Compound B (PIB), rapidly
crosses the blood brain barrier and is retained by ß-amyloid fibrils
but not in normal brain tissue. In Alzheimer’s patients, the high
contrast images show marked retention of PIB in areas where ß-amyloid
is characteristically found, such as the parietal and frontal cortices.
In contrast, patients with fronto-temporal dementia have
normal-appearing PIB images.
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Interestingly, PIB binding is seen in approximately 20% of apparently
normal older subjects, and whether this is an indication of antecedent
AD is a topic of intense investigation. PIB-PET also has applications
in drug development because it can be used to demonstrate whether drugs
that are designed to act on ß-amyloid, which are currently in
development, reduce or stabilize the burden of ß-amyloid plaque.
At this time, both proton MRS and PIB-PET are research tools. However,
with the recent dramatic advances in understanding the biology of AD
and the expectation that drugs will become available to treat it, these
neuroimaging tools will likely be brought into the clinical mainstream
for early diagnosis and intervention.
Scheduling
MRI or CT for evaluation of patients with dementia may be ordered
through ROE for appointments at the MGH Main Campus, Mass General West
Imaging Waltham, and Mass General Imaging Chelsea, or by telephone at
617-724-XRAY (9729) for all locations.
FDG PET may be ordered by telephone at 617-724-7212 after the completion of a scheduling worksheet documenting the diagnosis evidence for AD and fronto-temporal dementia and the potential benefits of FDG PET imaging.
Further Information
For further questions, please contact Ramon Gilberto Gonzalez, M.D., Ph.D., Chief of the
Division of Neuroradiology, MGH Department of Radiology at
617-726-8628.
We would like to thank Dr. Gonzalez and Keith Johnson, M.D.,
Neurologist and Radiologist, Nuclear Medicine Division, MGH Department
of Radiology, for their assistance and advice for this issue.
This article provided useful information about the appropriate use of imaging studies:
 
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