Abstract
BACKGROUND AND PURPOSE: Different biomarkers for AD may potentially be complementary in diagnosis and prognosis of AD. Our aim was to combine MR imaging, FDG-PET, and CSF biomarkers in the diagnostic classification and 2-year prognosis of MCI and AD, by examining the following: 1) which measures are most sensitive to diagnostic status, 2) to what extent the methods provide unique information in diagnostic classification, and 3) which measures are most predictive of clinical decline.
MATERIALS AND METHODS: ADNI baseline MR imaging, FDG-PET, and CSF data from 42 controls, 73 patients with MCI, and 38 patients with AD; and 2-year clinical follow-up data for 36 controls, 51 patients with MCI, and 25 patients with AD were analyzed. The hippocampus and entorhinal, parahippocampal, retrosplenial, precuneus, inferior parietal, supramarginal, middle temporal, lateral, and medial orbitofrontal cortices were used as regions of interest. CSF variables included Aβ42, t-tau, p-tau, and ratios of t-tau/Aβ42 and p-tau/Aβ42. Regression analyses were performed to determine the sensitivity of measures to diagnostic status as well as 2-year change in CDR-SB, MMSE, and delayed logical memory in MCI.
RESULTS: Hippocampal volume, retrosplenial thickness, and t-tau/Aβ42 uniquely predicted diagnostic group. Change in CDR-SB was best predicted by retrosplenial thickness; MMSE, by retrosplenial metabolism and thickness; and delayed logical memory, by hippocampal volume.
CONCLUSIONS: All biomarkers were sensitive to the diagnostic group. Combining MR imaging morphometry and CSF biomarkers improved diagnostic classification (controls versus AD). MR imaging morphometry and PET were largely overlapping in value for discrimination. Baseline MR imaging and PET measures were more predictive of clinical change in MCI than were CSF measures.
Abbreviations
- Aβ42
- β amyloid 1–42
- AD
- Alzheimer disease
- ADNI
- Alzheimer's Disease Neuroimaging Initiative
- AUC
- area under the curve
- B
- B coefficient for each predictor in the regression equation
- CDR-SB
- Clinical Dementia Rating sum of boxes
- Corr. Class.
- correlation classification
- CSHC
- Center for the Study of Human Cognition
- FDA
- US Food and Drug Administration
- 18F-FDG
- [18F] fluorodeoxyglucose
- FDG-PET
- fluorodeoxyglucose–positron-emission tomography
- inf.
- inferior
- lat.
- lateral
- LM-del
- delayed Logical Memory from the Wechsler Memory Scale Logical Memory II
- M
- mean
- MCI
- mild cognitive impairment
- med. orb. front.
- medial orbital frontal
- mid
- middle
- MMSE
- Mini-Mental State Examination
- MRI
- MR imaging
- NIH
- National Institutes of Health
- NC
- healthy control
- orb. front.
- orbital frontal
- p-tau
- phosphorylated tau protein 181
- parahippoc.
- parahippocampus
- PET
- positron-emission tomography
- t-tau
- tau protein
- ROC
- receiver operating characteristics
- Copyright © American Society of Neuroradiology
Indicates open access to non-subscribers at www.ajnr.org