PET Shows Potential in Identifying Earliest Stages of Dementia

By Charles Bankhead
NEW YORK, March 7 -- PET imaging with the glucose analog 18F-FDG distinguished different forms of dementia and separated them from mild cognitive impairment with greater than 90% accuracy, according to results of a multicenter trial.
Alzheimer's disease and other forms of dementia, Lisa Mosconi, Ph.D., of New York University, and colleagues, reported in the March issue of the Journal of Nuclear Medicine.
"The present study demonstrates the feasibility of using 18F-FDG PET in the differential diagnosis of the major neurodegenerative disorders, including mild and moderate-to-severe dementia patients, and in the characterization of [mild cognitive impairment] across multiple sites," the authors said.
Identification of different FDG PET profiles among subgroups of patients supports observations of heterogeneous cognitive deficits and clinical outcomes across the spectrum of patients with mild cognitive impairment, they added.
PET imaging of cerebral glucose metabolism is often used to support the clinical diagnosis of a major neurodegenerative disorder, such as Alzheimer's disease, the researchers said.
In particular, 18F-FDG PET has been proposed as an imaging modality to support the early and differential diagnosis of dementia, the authors said. The rationale has come from evidence that conditions such as Alzheimer's, frontotemporal dementia, and dementia with Lewy bodies are associated with specific patterns of regional glucose hypometabolism.
Widely considered a prodrome to dementia, mild cognitive impairment has attracted increased attention as a target of 18F-FDG PET imaging.
In the current study, investigators at seven centers evaluated 548 patients ages 50 to 85. The study population comprised 114 individuals diagnosed with mild cognitive impairment, 199 with Alzheimer's disease, 27 with dementia with Lewy bodies, 98 with frontotemporal dementia, and 110 age-matched controls without cognitive impairment.
All patients with dementia diagnoses met DSM-IV diagnostic criteria. The diagnosis of mild cognitive impairment was based on clinical interview and several validated assessment instruments. The control group underwent the same type of assessment as did the patients with mild cognitive impairment.
PET imaging was performed by means of standard imaging protocols at all seven participating centers. Interpretation centered on patterns of cortical and hippocampal uptake.
The results showed that disease-specific PET patterns correctly classified:
95% of patients with Alzheimer's disease
92% of patients with dementia with Lewy bodies
94% of patients with frontotemporal dementia
94% of the control group
Among patients with mild cognitive impairment, 81% exhibited predominant cingulate cortex and hippocampal hypometabolism, whereas neocortical abnormalities varied by neuropsychologic profile.
The authors observed an Alzheimer's disease PET pattern in 79% of mildly impaired patients with deficits in multiple cognitive domains and in 31% of patients with amnesic mild cognitive impairment.
A positive PET scan for any neurodegenerative disorder discriminated mild cognitive impairment from the control group with 86% sensitivity, 96% specificity, and 92% overall accuracy, the authors said.
About two thirds of the mildly impaired patients exhibited bilateral reductions in FDG uptake.
Little is known about the potential for 18F-FDG PET as a diagnostic tool for mild cognitive impairment, the authors said. They noted that this study showed that patterns of regional glucose metabolic abnormalities accurately distinguished mild cognitive impairment from the control group.
The authors pointed out the value of the development of automated techniques. "At present, a limitation to the use of PET in clinical practice is the reliance on qualitative interpretation of the images by visual reading. Visual ratings depend heavily on the observer's experience and training, and 18F-FDG PET measures often lack clearly defined cutoffs to distinguish between normal and pathologic findings," they said.
"The present study shows that objective image analysis procedures can be easily applied and shared across different PET centers, thanks to the development of voxel-based automated techniques for diagnostic examinations and of reliable normative databases," they concluded.
The authors reported no disclosures.
Primary source: Journal of Nuclear MedicineSource reference:Mosconi L, et al "Multicenter standardized 18F-FDG PET diagnosis of mild cognitive impairment, Alzheimer's disease, and other dementias" J Nucl Med 2008; 49: 390-398.