Evaluation of a calibrated (18)F-FDG PET score as a biomarker for progression in Alzheimer disease and mild cognitive impairment.

Abstract

UNLABELLED:

Increasingly, clinical trials are being planned in patients with mild cognitive impairment (MCI) to prevent or delay the onset of dementia in Alzheimer disease (AD) by disease-modifying intervention. Inclusion of imaging techniques as biomarkers for patient selection and assessment of outcome is expected to increase trial efficacy. PET using (18)F-FDG provides objective information about the impairment of synaptic function and could, with appropriate standardization, qualify as a biomarker.

METHODS:

We evaluated a predefined quantitative measure (PET score) that is extracted automatically from (18)F-FDG PET scans using a sample of controls (n = 44), patients with MCI (n = 94), and patients with mild AD (n = 40) from the Alzheimer Disease Neuroimaging Initiative (ADNI). Subjects received 4 scans and clinical assessments over 2 y.

RESULTS:

PET scores provide much higher test-retest reliability than standard neuropsychologic test scores (Alzheimer's Disease Assessment Scale-Cognitive [ADAS-cog] and Mini-Mental State Examination) and superior signal strength for measuring progression. At the same time, they are related linearly to ADAS-cog scores, thus providing a valid measure of cognitive impairment. In addition, PET scores at study entry in MCI patients significantly predict clinical progression to dementia with a higher accuracy than Mini-Mental State Examination and ADAS-cog.

CONCLUSION:

(18)F-FDG PET scores are a valid imaging biomarker to monitor the progression of MCI to AD. Their superior test-retest reliability and signal strength will allow the reduction in the number of subjects needed or shortening of study duration substantially.

• Authors: Karl Herholz, Sarah Westwood, Cathleen Haense, Graham Dunn
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 52 Issue 8 Pg. 1218-26 (Aug 2011) ISSN: 1535-5667 [Electronic] United States
• PMID: 21764801 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Biomarkers
• Fluorodeoxyglucose F18

Topics

• Aged
• Alzheimer Disease (diagnostic imaging, pathology)
• Biomarkers (metabolism)
• Calibration
• Cognition
• Cognition Disorders (diagnostic imaging, pathology)
• Disease Progression
• Female
• Fluorodeoxyglucose F18 (pharmacology)
• Humans
• Male
• Mental Status Schedule
• Middle Aged
• Neurology (methods)
• Neuropsychological Tests
• Positron-Emission Tomography (methods)
• Reproducibility of Results