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ADNI Update– Utah Analysis Laboratory, PET Core

ADNI Update– Utah Analysis Laboratory, PET Core. Norman L. Foster, M.D. University of Utah, Salt Lake City, UT. Utah Analysis Laboratory. 3D-Stereotactic Surface Projection (3D-SSP) Results of topographic extent of significant hypometabolism (group data) Findings on individual case analysis

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ADNI Update– Utah Analysis Laboratory, PET Core

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  1. ADNI Update– Utah Analysis Laboratory, PET Core Norman L. Foster, M.D. University of Utah, Salt Lake City, UT

  2. Utah Analysis Laboratory 3D-Stereotactic Surface Projection (3D-SSP) Results of topographic extent of significant hypometabolism (group data) Findings on individual case analysis FDG-PET correlates of MCI conversion to AD Summary of major findings Hypotheses we plan to test

  3. Utah Analysis: 3-Dimensional Stereotactic Surface Projection (3D-SSP) Maps with Neurostat • Scan rotated and warped into a uniform space • Vectors constructed perpendicular to approximately 16,800 predefined pixels on the outer and medial brain surfaces • Maximum value on each vector is projected to the brain surface • Using peak rather than average values make results relatively resistant to effects of atrophy • Surface values normalized to Pons • Z-score maps in comparison to reference population

  4. Alzheimer’s Disease

  5. Topographic Extent of Hypometabolism at Baseline Is Intermediate inaMCI # of Significant Pixels (Z>3) Diagnosis at Baseline • aMCI (n = 161) • 217 ± 307 • AD (n = 75) • 579 ± 865 (p< 0.001) • CN (n = 80) • 86 ± 152 (p< 0.01) Median and quartile plots

  6. Case-by-Case Image Analysis • Grouped data show typical, symmetric pattern • Individual analysis reveals remarkable pattern variability

  7. Background • Long-standing concern that studies of Alzheimer’s disease (AD) could be contaminated with other disorders • Frontotemporal dementia (FTD) and AD are difficult to distinguish clinically • Patients with FTD often meet NINCDS-ADRDA criteria for probable AD

  8. Simple Rules for Classification 98% specificity for FTD in autopsy-confirmed cases; Foster et al. Brain 2007; 130: 2616-35.

  9. Results • 10 of 93 subjects (10.8%) had metabolic patterns classified as FTD

  10. FTD-like Pattern is Heterogeneous

  11. Characteristics of Subjects with FTD-like Metabolic Pattern • All from different clinical sites • No significant demographic differences • 6 men, 4 women • Slightly older (78.9 ± 6.7 vs 75.3 ± 7.3) • No significant cognitive test differences • Lower MMSE (21.6 ± 1.8 vs 23.8 ± 2.2) • Lower Immediate Logical Memory (4.0 ± 2.8 vs 1.9 ± 1.5) • Higher NPI (5.0 ± 4.0 vs 4.0 ± 3.5)

  12. Hypometabolism is More Extensive in MCI Subjects Converting to AD by 1 Year # of Significant Pixels • Remain MCI at 1 year • N=138 (92 men, 46 women) • Age: 75.4 ± 6.5 • Pixels: 217 ± 307 • Convert to AD by 1 year • N=23 (14 men, 9 women) • Age: 75.3 ± 6.5 • Pixels 511 ± 627 (p< 0.02) Median and quartile plots

  13. In MCI Extent of Hypometabolism Predicted Timing of Conversion • Conversion to AD at 6 months: N=5 • # Significant Pixels 1128 ± 1000 • Conversion to AD at 12 months: N=18 • # Significant Pixels 340 ± 363 • Remain MCI at 12 months: N=138 • # Significant Pixels 168 ± 283

  14. Extent of Significant Hypometabolism at Baseline Predicts Timing of Conversion to AD inaMCISubjects

  15. Major Findings – Utah Component, PET Core Topographic extent of hypometabolism is a promising outcome measure showing group differences and correlation with dementia severity While AD patients on average have symmetric hypometabolism, individual patients may have dramatic hemispheric asymmetry About 10% of clinically diagnosed AD patients have an FTD-like pattern of hypometabolism The extent of hypometabolism at baseline in aMCI predicts likelihood and timing of conversion to AD

  16. Hypotheses to Test – Utah Component, PET Core • 3D-SSP can aid analysis of AV-45 scans by: • Limiting analysis to peak cortical areas, minimizing effects of atrophy • Providing statistical Z-score displays • Individual differences in regional amyloid binding explain patterns of glucose hypometabolism • ADNI AD subjects with FTD-like pattern don’t have increased amyloid binding • Baseline patterns of asymmetry and topographic extent of hypometabolism have prognostic value

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