Alzheimer’s Disease is an irreversible, degenerative brain disease that is marked by the build up of plaque and tangles in the neurons of Alzheimer’s patients, which induce memory loss and inhibit mental functions. Estimates vary, but experts believe as many as 5.1 million Americans are currently suffering from Alzheimer’s (Alzheimer’s Fact Sheet). Although there is no cure for the disease, early detection of Alzheimer’s is crucial because it allows the patient to immediately begin a drug regimen that slows the process of the disease. In modern medicine, two types of PET imaging, fluorodeoxyglucose and amyloid, are the most effective methods of diagnosing Alzheimer’s Disease. The degenerative aspect of Alzheimer’s is caused by plaque and tangles in the nerve cells of the brain. Abnormal clusters of protein fragments called beta amyloid accumulate in the synaptic gap between neurons and block cell-to-cell signaling (Alzheimer’s Association). This build up of plaque may also activate an autoimmune response, which kills the deactivated cells (Medicine Net). Simultaneously, tangles in a protein called tau destroy a vital nerve cell transport system. Healthy transport systems are kept orderly and parallel by tau (Alzheimer’s Association). In Alzheimer’s patients, however, tau collapses in to twisted strands called tangles. The transport system can no longer stay parallel, which causes it to disintegrate. Key materials like food molecules and cell parts can no longer move through the cells, so the neurons eventually die. These two phenomena result in widespread cell death and tissue loss that cause the brain to shrink. The cortex shrivels, damaging areas of the brain involved in thinking, planning, and remembering (Alzheimer’s Association). Especially severe shrinkage occurs in the hippocampus, an area of the cortex that plays a key role in the formation of new memories (Alzheimer’s Association). Medication for the treatment of Alzheimer’s can slow the process of cell death and subsequent brain tissue loss by regulating chemical messengers in the brain that are important for cell memory. Cholinesterase inhibitors are one such class of drug, which prevents the breakdown of acetylcholine (Alzheimer’s Association), a critical neurotransmitter involved in the initial formation of memory (Animal Behavior Online). Cholinesterase inhibitors are generally prescribed for patients in the early stages of Alzheimer’s because they are most effective at reducing the speed of cell death (Alzheimer’s Association). As the disease progresses, the brain produces less acetylcholine, so cholinesterase inhibitors eventually lose their effect (Alzheimer’s Medication Fact Sheet). For patients with severe Alzheimer’s, doctors recommend a different type of drug. A medication called memantine regulates the activity of glutamate, a different neurotransmitter involved in learning and memory (Alzheimer’s Association). Memantine works in much the same way as cholinesterase inhibitors, but has generally more severe side effects, so it is reserved for the final stages of Alzheimer’s. PET imaging can diagnose Alzheimer’s earlier than conventional methods and, therefore, can maximize the amount of time cholinesterase inhibitors are effective for the patient. This is important because it provides the patient with considerably more time to prepare logistically, financially, and psychologically for the future. Patients who are diagnosed in the earliest stages of disease by PET imaging are afforded comfort, dignity, and independence for longer periods of time than patients who are diagnosed by clinical methods like memory tests or urine screenings. Positron emitting tomography (PET) imaging is the most effective neuroimaging method used in screening for Alzheimer’s Disease. PET imaging is a type of nuclear medicine. The patient ingests or is injected intravenously with a small amount of radioactive material called a radiotracer that accumulates in the part of the body being examined (Radiology Info). For Alzheimer’s patients, the radiotracer gathers in the brain and gives off gamma rays. These rays are detected by the PET scanner and used to produce an image. The radiotracer used in a PET scan can vary based on what kind of activity is being examined. For example, there are two types of radiotracers commonly used to diagnose Alzheimer’s. One measures the relative amount of metabolic activity in the brain, and the other determines the amount of beta amyloid present between the neurons. Even though these two types of PET imaging use different radiotracers, they can both reliably diagnose Alzheimer’s. Standard FDG-PET scans assess brain activity by measuring the amount of glucose taken up by the brain in proportion to the metabolic activity. Fluorodeoxyglucose, abbreviated FDG, combines a radionuclide that has a measurable level of radioactivity with a glucose substrate that is taken up by high-glucose-using cells like neurons (FDG Facts). Once the FDG enters the nerve cell, it undergoes phosphorylation to prevent the neuron from releasing the glucose after it was absorbed (FDG Facts). The tissues with the highest metabolic activity retain the FDG best, so those areas appear brightest on the PET scan. Research of FDG-PET imaging has shown that measuring the uptake of sugar in the brain significantly improves the accuracy in differentiating between Alzheimer’s and a type of dementia that is often mistaken for Alzheimer’s. A study led by Normal L. Foster, M.D., professor of neurology and director of the Center for Alzheimer’s Care, Imaging, and Research at the University of Utah School of Medicine proved that FDG-PET imaging helped six doctors from three national Alzheimer’s disease centers correctly diagnose frontotemporal dementia and Alzheimer’s in almost 90 percent of the cases in the study (Science Daily). This is an improvement of as much as 14 percent from usual clinical diagnostic methods (Science Daily). 45 individuals were asked to participate in the study. These patients all received autopsies to confirm the results of the study. The expert neurologists were asked to decide whether each patient was suffering from frontotemporal dementia or Alzheimer’s using clinical information alone or using FDG-PET images (Science Daily). Frontotemporal dementia and Alzheimer’s meet the same clinical diagnostic criteria, so it is often difficult even for experts to distinguish between the two forms of dementia using only clinical methods. According to this study, FDG-PET imaging can help the physicians differentiate between frontotemporal dementia and Alzheimer’s with relative ease. In frontotemporal dementia, low activity is located mostly in the front of the brain, which shows up dark on the FDG-PET scan. These PET scans are in direct contrast with the scans of Alzheimer’s patients who have low activity centered in the back of the brain around the hippocampus. FDG-PET scans increased the experts’ confidence in a correct diagnosis in 42 percent of the cases in the study (Science Daily). While Dr Foster’s research proved that FDG-PET imaging is a powerful tool in the early detection of Alzheimer’s Disease, it is equally important to remember that this type of PET imaging is very generic. Low metabolic activity in the brain can be caused by multiple reasons including seizure or stroke (Radiology Info), so dark regions in the brain does not automatically validate an Alzheimer’s diagnosis.
Amyloid PET imaging techniques are gradually becoming more popular in the medical community because they are much more specific that FDG-PET imaging and may be even more effective. These types of PET scans use a radiotracer called Pittsburgh Compound B, or PIB. This compound binds to the plaque-forming beta amyloid in the brains of Alzheimer’s patients (Health Blog). Highly concentrated regions of beta amyloid show up brightest in the PET image. Physicians favor this type of PET scan because it is highly specific. There is no threat of mistaking Alzheimer’s with other mild types of dementia caused by normal aging because dementia does not form plaque in the brain. Unfortunately, the compound PIB is based off the radioactive isotope carbon-13, which has a half-life of 20 minutes (Health Blog). This means that in a mere twenty minutes, half of the radiotracer is degraded and unusable. Logistical concerns are obviously a major obstacle in amyloid PET imaging. Health care workers have a small time frame to work with PIB. Also, the short half-life creates complications in transporting the compound from the manufacturer to the hospitals, which can be over one hundred miles away. Because of the obvious potential in amyloid PET imaging for the diagnosis of Alzheimer’s, Dean F. Wong, M.D., Ph.D., professor of radiology and psychiatry at the Johns Hopkins University School of Medicine, developed a radiotracer with a substantially longer half-life than PIB. This compound called 18F-AV-45, or florbetapir F18, is based off the fluorine-18 isotope (Health Blog). Florbetapir binds to the beta amyloid the same way as the Pittsburgh Compound, but it has a half-life of 110 minutes (Health Blog). The longer half-life of florbetapir provides physicians and PET scan technicians with more time to perform each PET scan. Florbetapir also helps solve the problem or transporting the compound to more remote hospital locations. Florbetapir has passed its first clinical tests and is moving closer to FDA approval. Christopher M. Clark, M.D., and a team of other researchers designed a study to determine if florbetapir PET imaging performed during a patient’s life accurately predicts the presence of beta-amyloid in the brain at autopsy (JAMA). Over a 13 month period, 35 patients near the end of their lives were evaluated using amyloid PET imaging with the radiotracer florbetapir F-18 (JAMA). The postpartum results agreed with the PET images 96 percent of the time (Health Imaging Hub). The study also provided a test to better understand the frequency of potential false positive interpretations of a florbetapir PET image. All 74 of the young individuals (18 to 50 years) presumed to be free of brain amyloid had amyloid negative PET scans using florbetapir (JAMA). This data correlates with a miniscule occurrence of false positive diagnoses in florbetapir PET scans. Promising results from studies like this help to further push florbetapir towards an FDA approval. PET imaging is a clear and efficient method for diagnosing Alzheimer’s, but like every other type of neuroimaging, it has drawbacks. One of the biggest concerns associated with PET imaging is radiation exposure. PET scans only use a minimal amount of radioactive material during the scan, however, so the radiation exposure is far less than that of a CT scan (Help With Cancer). Also, PET scans require cyclotrons, machines that synthesize and store the radioactive isotopes used to create the radiotracers (Radiology Info). Cyclotrons are large, expensive, and cumbersome, so PET scans are unavailable in the majority of medical centers around the world (Radiology Info), especially in developing countries with poor health care infrastructure. Another limitation of PET imaging is the cost. PET scans are a relatively new medical procedure, and have an average cost ranging from $900 to $1400 (Radiology Info). Despite these few downsides, PET imaging is an extremely effective method of diagnosing Alzheimer’s Disease - one that is not utilized often enough in the modern medical community. The degenerative nature of Alzheimer’s highlights the importance of early diagnosis. The sooner patients are diagnosed, the sooner they can begin a drug regime to slow the process of the disease and maximize their remaining years of independence. Big steps have been taken in the field of neuroimaging to improve the effectiveness of both FDG-PET scans and amyloid PET scans in diagnosing Alzheimer’s. Hopefully, in the years to come, PET imaging will continue to improve and result in even earlier Alzheimer’s diagnoses. Perhaps PET imaging will even provide clues to the origin of the disease and point scientists in the right direction towards finding a cure.