SNM 2009: PET Can Be Used to Classify Dementia Subtype

Louise Gagnon

June 23, 2009

June 23, 2009 (Toronto, Ontario) — Preliminary results of an ongoing study show that the use of positron emission tomography (PET) can help improve the accuracy of a dementia diagnosis.

We know that dementia is misdiagnosed," Kirk Frey, MD, professor of radiology and psychiatry at the University of Michigan Hospitals' Division of Nuclear Medicine in Ann Arbor, said in an interview here at the Society of Nuclear Medicine 56th Annual Meeting. To date, "the best way [to diagnose it is] to compare the clinical diagnosis with what is found at autopsy."

Study subjects diagnosed with mild cognitive impairment or mild dementia (Mini-Mental State Examination score ≥ 18) received standard neurological, neuropsychometric, and anatomic brain-imaging evaluations. Three experts in the field were asked to evaluate the results. They arrived at a diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), or dementia with Lewy bodies (DLB).

Investigators performed PET imaging with both carbon-11-labelled Pittsburgh-compound B (11C-PiB) to detect amyloid deposits and [11C]dihydrotetrabenazine (DTBZ) to measure nigrostriatal projection integrity. Individuals with FTD showed normal uptake of both PiB and DTBZ. Individuals with DLB showed severe striatal DTBZ defects. Those with AD had normal DTBZ uptake and augmented frontal cortical PiB binding.

There was a lack of agreement between clinical evaluations and PET classifications in 26% of subjects. Specifically, 3 of 9 patients had nigrostriatal lesions on PET that were not identified clinically. Nine of 43 patients were positive for PiB but were not clinically diagnosed as such, and 3 of 14 FTD patients were incorrectly classified, based on clinical findings, as having AD.

Dr. Frey described the rate of misdiagnosis as "significant." "If you take the imaging as truth, our clinical diagnosis was in error 24% of the time, which is well within the range of what clinical autopsy studies that have been previously published found," said Dr. Frey.

The researchers plan to compile 2 years of data on 150 patients who are currently being followed. "The patients are being followed longitudinally," said Dr. Frey. "It could be that the clinical diagnosis may be different after 2 years."

The consequence of misdiagnosis can be inappropriate management of patients, he cautioned.

"In the clinic, it is often impossible [clinically] to distinguish between DLB and Alzheimer's disease," said Dr. Frey in an interview with Medscape Radiology. "These patients have a degeneration of their dopamine neurons, as well as the nerve cells in the forebrain, that relate to cognitive decline.

"If you have such a patient and you don't know the patient has DLB, you may administer an antipsychotic medication to help with behavioral management," explained Dr. Frey. "In these patients, that can be lethal."

Similarly, acetylcholinesterase inhibitors, which are frequently prescribed for symptom management of dementia, are believed now to be more effective in treating DLB than AD and are regarded as having no benefit in treating FTD, according to Dr. Frey.

"This is not necessarily a safety risk from the standpoint of the patient, but unnecessary use of acetylcholinesterase inhibitors is a significant expense to the patient or the healthcare system," said Dr. Frey.

Moreover, being able to identify the subtypes of dementia using PET with emerging imaging tracers will open the research door to more targeted therapies and narrow the study populations to more suitable candidates. "If the drug is targeting an amyloid pathology, you would want to restrict a trial of that drug to patients who have the amyloid problem," said Dr. Frey.

He stressed that clinically approved radiotracers are not able to identify neurochemical features that differentiate between dementia subtypes and that the tracers used in this study are not yet approved by the US Food and Drug Administration.

"It is a very relevant study," said Alexander Drzezga, MD, a visiting assistant professor in the Department of Radiology at Harvard University/Massachusetts General Hospital in Boston, who moderated the oral session at which the research was presented. "There is a benefit of imaging procedures in cases that are not clear. Even experienced clinicians may judge the cases wrong."

Dr. Drzezga said it does occur in clinical practice that patients are prescribed inappropriate medications because of inappropriate disease classification.

"It's good to have measures that give you an objective answer," said Dr. Drzezga. "The symptoms can be misleading, and imaging may give you a more definite proof of what patients are suffering from."

Dr. Frey and Dr. Drzezga have disclosed no relevant financial relationships.

Society of Nuclear Medicine 2009 Annual Meeting, Abstract 251. Presented June 15, 2009.
J Nuclear Med. 2009;50:65P.

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