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PET's Molecular Imaging Power May Be Best Indicator for Determining Which Patients Develop Alzheimer's

October 06, 2005

Imaging With Radiotracer FDG in Patients With Mild Cognitive Disorder Has Significantly Higher Accuracy Than Genetic Screening, Says Study in Journal of Nuclear Medicine

RESTON, Va.-Positron emission tomography (PET) imaging-with the radiotracer fluorodeoxyglucose (FDG)-is a promising tool in detecting Alzheimer's disease in patients who have mild cognitive impairment (MCI), according to a study reported in the October issue of the Society of Nuclear Medicine's Journal of Nuclear Medicine.

"PET imaging with FDG represents one of the most promising tools for diagnosis of Alzheimer's," said Alexander Drzezga, M.D., who is the senior physician with the department of nuclear medicine at the Technical University of Munich in Germany. In fact, using PET imaging with FDG "may be the best indicator for determining which MCI patients are most at risk of developing Alzheimer's," added the lead author of "Prediction of Individual Clinical Outcome in Mild Cognitive Impairment (MCI) by Means of Genetic Assessment and 18F-FDG PET."

Mild cognitive impairment (MCI) is a term used to describe a subtle but measurable deterioration of cognitive capabilities, such as memory function. Individuals with MCI are able to function reasonably well in everyday activities, such as managing finances and purchasing items at stores without assistance, but may have difficulty remembering details of conversations, events and upcoming appointments.

Patients with MCI do not yet exhibit the criteria for the diagnosis of dementia, but the disorder is seen as a precursor to Alzheimer's disease, which takes years to develop in a person, said Drzezga. Many patients with MCI develop a progressive decline in their thinking abilities over time, and Alzheimer's disease is usually the underlying cause. Alzheimer's is the most common form of dementia among older people; it is a progressive, irreversible brain disorder with no known cause or cure. More than 4.5 million Americans suffer from Alzheimer's and its symptoms of memory loss, confusion, impaired judgment, personality changes, disorientation and loss of language skills.

"A high percentage of MCI patients will develop Alzheimer's disease within a year; however, some of these patients will never develop dementia and may even improve with time," said Drzezga. Most MCI patients who showed abnormalities typical of Alzheimer's in their original PET scan developed dementia within 16 months, according to findings from the 30-patient study. Most patients who did not show abnormalities in their original PET scan remained stable, he added.

Patients with Alzheimer's show characteristic changes of the cerebral glucose metabolic pattern, with a decrease in affected brain regions, said Drzezga. PET imaging with FDG allows the analysis of regional cerebral glucose metabolism. The study showed that "the assessment of cerebral glucose metabolism actually reflects ongoing pathological changes associated with Alzheimer's disease on a molecular level and that the molecular imaging method PET is capable of depicting subtle changes in the brain of MCI patients before a diagnosis of Alzheimer's based on neuropsychological evaluation is possible," said Drzezga.

The study revealed that PET with FDG has a significantly higher accuracy for detection of Alzheimer's than the genetic screening for the APOEe4-risk factor. In addition, using both PET with FDG and the APOEe4-genotype as genetic markers "allowed the definition of subgroups of patients with very high risk and with very low risk," he added. This finding could have implications for risk stratifying MCI patients in therapeutic trials, said Drzezga. "This study implies that PET-and in consequence nuclear medicine-should continue to be strongly involved in the challenging process of Alzheimer's research for early diagnosis as well as for the development and evaluation of new treatment options," he added.

Although there is currently no cure for Alzheimer's, new treatments are on the horizon as a result of accelerating insight into the biology of the disease. "It is of increasing importance to identify 'converters' at the earliest possible stage of disease to develop and evaluate new and upcoming treatment options for Alzheimer's," added Drzezga, an SNM member.

PET is a safe, effective and painless biological imaging exam that "photographs" or detects the presence and extent of neurological conditions. PET uses very small amounts of radioactive materials that are targeted to specific organs, bones or tissues. Radiotracers (such as FDG) are injected and then detected by a special type of camera that works with computers to provide precise pictures of the area of the body being imaged and molecular images of the body's biological functions. "The combination of molecular imaging with genotype assessment represents the unique opportunity to interpret imaging findings in the context of background information," explained Drzezga. "As we increase our understanding of the human genome, individualized therapy and individualized diagnosis will become increasingly important," he added. "The current study underlines that a genetic disposition does not necessarily represent a determined prognosis, thus, the need for measures that allow the definition of the actual onset of a disease process is apparent. Molecular imaging could play an important role in this context," he stated.

"Prediction of Individual Clinical Outcome in Mild Cognitive Impairment (MCI) by Means of Genetic Assessment and 18F-FDG PET" appears in the October issue of the Journal of Nuclear Medicine, which is published by the Society of Nuclear Medicine. Besides Drzezga, authors include Markus Schwaiger, M.D., department of nuclear medicine, Technical University of Munich, Germany; Timo Grimmer, M.D., Matthias Riemenschneider, M.D., Panagiotis Alexopoulus, M.D., and Alexander Kurz, M.D., all with the department of psychiatry and psychotherapy, Technical University of Munich, Germany; Nicola Lautenschlager, M.D., school of psychiatry and clinical neurosciences, University of Western Australia, Crawley, Australia; Hartwig Siebner, M.D., department of neurology, Christian-Albrechts-University, Kiel, Germany, and NeuroImage-Nord, Hamburg, Germany; and Satoshi Minoshima, M.D., Ph.D., department of radiology, University of Washington, Seattle.

Society of Nuclear Medicine