Alzheimer's Disease FAQs (cont.)
Norberto Alvarez, MD
Melissa Conrad Stöppler, MD, Chief Medical Editor
Melissa Conrad Stöppler, MD, Chief Medical Editor
Melissa Conrad Stöppler, MD, is a U.S. board-certified Anatomic Pathologist with subspecialty training in the fields of Experimental and Molecular Pathology. Dr. Stöppler's educational background includes a BA with Highest Distinction from the University of Virginia and an MD from the University of North Carolina. She completed residency training in Anatomic Pathology at Georgetown University followed by subspecialty fellowship training in molecular diagnostics and experimental pathology.
IN THIS ARTICLE
How can Alzheimer's disease be diagnosed?
Traditionally it was accepted that only a brain biopsy or an autopsy was able to confirm the diagnosis of Alzheimer's disease. This is still valid today; however the past 20 to 25 years have seen an increase in the study and evaluation of methods that can help to diagnose Alzheimer's disease in individuals before clinical symptoms are observed. The goal is to identify the persons that will develop Alzheimer's disease in the preclinical stages in order to be able to treat them before the disease develops to the clinical stage.
There are functional and structural changes in the areas of the brain were the senile plaques and the neurofibrillary tangles deposit. These structural changes as well as the functional changes can be documented by specific imaging tests.
Among these tests are those that measure structural changes in the brain like a CT scan and MRI; those that measure functional changes like brain glucose metabolism, as is the case with Positron Emission Tomography (FDG-PET), and more recently those tests that can specifically measure biochemical changes that are related to Alzheimer's disease as is the deposition of amyloid in the brain with special markers (PET PIB).
Besides, new studies in biological fluids, specifically in the cerebrospinal fluid (CSF) have also added useful information that might help to predict who may develop Alzheimer's disease.
Brain MRIs or CT scans might show brain changes such as diffuse or focal atrophy, while not diagnostic of Alzheimer disease, are considered a valid biomarker of Alzheimer disease neuropathology.
Functional MRI (fMRI) evaluates the brain function by measuring the level of oxygenated hemoglobin in the brain. In Alzheimer's disease, fMRI shows areas in the brain with decreased activity that are associated with Alzheimer's disease.
PET requires the administration, usually intravenously, of a radioactive tracer. This test allows the measurement of metabolic function, brain metabolism, and binding to specific receptors in the brain. One of the most common tracers is fluorodeoxyglucose (FDG), which is glucose marked with a radioactive material [18 F]. FDG PET may detect changes in the brain in individuals prone to have Alzheimer's disease before they develop clinical symptoms of Alzheimer's disease.
Another radioactive material that can be used as a tracer is known as Pittsburgh Compound B (PIB). This tracer has affinity with the amyloid protein. The PET PIB study might be of great utility to determine the extension of the deposits of beta amyloid in the brain.
In addition ot their locations within the brain, the amyloid A beta 1-42 as well as the Tau proteins are also found in the liquid that bathes the surface of the brain, the cerebrospinal fluid (CSF). Samples of CSF can be easily obtained with a lumbar puncture or spinal tap. This is a relatively simple and safe procedure that consists of inserting a needle through the space between the lumbar vertebrae in the lower back. In general no anesthesia is needed, but sometimes a mild sedative is more than enough to perform the procedure. The analysis of the amyloid A beta 1-42 protein and the Tau protein in the CSF may yield important information regarding Alzheimer's disease.
Studies of the CSF have shown that a pattern of low level of amyloid A beta 1-42 protein combined with high level of the Tau and phosphorylated Tau protein was detected in the majority (90%) of persons with clinical Alzheimer's disease; however, the same pattern was found in 39% of normal individuals. In persons with mild cognitive impairment (MCI) but no clear Alzheimer's disease the presence of the same pattern correctly identified the people that later on would develop Alzheimer's disease.
However other clinical conditions might also produce similar results. For example deposits of amyloid A beta 1-42 can be seen in Parkinson's disease, in another form of dementia called Lewy Body disease, and also in cognitively normal individuals. Furthermore, a high concentration of Tau proteins may be seen after acute stroke or traumatic brain injuries.
Some studies also suggest that these biomarkers may have prognostic value. The rate of deterioration may be faster in those with extremely abnormal results.
In summary the radiological tests as well as measuring amyloid A beta 1-42 protein and Tau protein in the CSF, even while not diagnostic of Alzheimer's disease, may become an important addition to other clinical information in the diagnosis and prognosis of Alzheimer's disease.
Who should get the tests?
The answer is not clear and an individual should consult with their doctor about the convenience of having these tests performed. Some physicians recommend the test when the diagnosis of Alzheimer disease will have important consequences, for example, when making decisions about lifestyle, end of life treatments, etc.
These tests can also help in the differential diagnosis with other forms of dementia that might have specific treatments available, such as normal pressure hydrocephalus or vascular dementia, or conditions that simulate dementia, as may be the case with severe clinical depression. However this should not be a common indication since in most instances these conditions can be diagnosed clinically or with other available methods.
At the present time these diagnostic tests will not change the prognosis of the disorder since no treatment is available. However if a treatment becomes available these tests would become very important and useful.
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