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

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

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

Patientswith MCI do not yet exhibit the criteria for the diagnosis of dementia,but the disorder is seen as a precursor to Alzheimer's disease, whichtakes years to develop in a person, said Drzezga. Many patients withMCI develop a progressive decline in their thinking abilities overtime, and Alzheimer's disease is usually the underlying cause.Alzheimer's is the most common form of dementia among older people; itis a progressive, irreversible brain disorder with no known cause orcure. More than 4.5 million Americans suffer from Alzheimer's and itssymptoms of memory loss, confusion, impaired judgment, personalitychanges, disorientation and loss of language skills.

"A highpercentage of MCI patients will develop Alzheimer's disease within ayear; however, some of these patients will never develop dementia andmay even improve with time," said Drzezga. Most MCI patients who showedabnormalities typical of Alzheimer's in their original PET scandeveloped dementia within 16 months, according to findings from the30-patient study. Most patients who did not show abnormalities in theiroriginal PET scan remained stable, he added.

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

Thestudy revealed that PET with FDG has a significantly higher accuracyfor detection of Alzheimer's than the genetic screening for theAPOEe4-risk factor. In addition, using both PET with FDG and theAPOEe4-genotype as genetic markers "allowed the definition of subgroupsof patients with very high risk and with very low risk," he added. Thisfinding could have implications for risk stratifying MCI patients intherapeutic trials, said Drzezga. "This study implies that PET—and inconsequence nuclear medicine—should continue to be strongly involved inthe challenging process of Alzheimer's research for early diagnosis aswell 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 insightinto the biology of the disease. "It is of increasing importance toidentify 'converters' at the earliest possible stage of disease todevelop and evaluate new and upcoming treatment options forAlzheimer's," added Drzezga, an SNM member.

PET is a safe,effective and painless biological imaging exam that "photographs" ordetects the presence and extent of neurological conditions. PET usesvery small amounts of radioactive materials that are targeted tospecific organs, bones or tissues. Radiotracers (such as FDG) areinjected and then detected by a special type of camera that works withcomputers to provide precise pictures of the area of the body beingimaged and molecular images of the body's biological functions. "Thecombination of molecular imaging with genotype assessment representsthe unique opportunity to interpret imaging findings in the context ofbackground information," explained Drzezga. "As we increase ourunderstanding of the human genome, individualized therapy andindividualized diagnosis will become increasingly important," he added."The current study underlines that a genetic disposition does notnecessarily represent a determined prognosis, thus, the need formeasures that allow the definition of the actual onset of a diseaseprocess is apparent. Molecular imaging could play an important role inthis context," he stated.

"Prediction of Individual Clinical Outcome in Mild Cognitive Impairment (MCI) by Means of Genetic Assessment and ¹⁸F-FDGPET" 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., MatthiasRiemenschneider, M.D., Panagiotis Alexopoulus, M.D., and AlexanderKurz, 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 WesternAustralia, Crawley, Australia; Hartwig Siebner, M.D., department ofneurology, Christian-Albrechts-University, Kiel, Germany, andNeuroImage-Nord, Hamburg, Germany; and Satoshi Minoshima, M.D., Ph.D.,department of radiology, University of Washington, Seattle.