1. Rosa Maria Moresco University of Milan Bicocca
Contribution of Imaging to the future understanding of loss of memory due to neurodegeneration
Rosa Maria Moresco
University of Milan Bicocca

2. In vivo Imaging Anatomy Function Molecules Knowledge Technology
Morphology
Connectivity
TAC, MRI,
Gray matter density
Fiber tracking DT-MRI
Perfusion
Metabolism
PET, fMRI, TAC perf.
Receptors
Enzymes
Proteins
PET SPET
Knowledge
Technology
Metodology

3. Brain glucose metabolism Typical Alzheimer disease pattern
HSR Milano

4. Typical Cerebral Metabolic Patterns Voxel-based analysis (SPM5)
in Neurodegenerative
Disorders R
Voxel-based analysis (SPM5)
96 patients
each group
vs. 18 HC
two sample t-test
The differential diagnosis of neurodegenerative diseases on clinical grounds is difficult, especially at an early stage. This study shows how a quantitative voxel-based analysis could identify disease-specific patterns of relatively decreased metabolic activity in degenerative patients. For example it is evident in DLB the involvement of occipital and parietotemporal regions, in AD parietotemporal regions, and in FTD frontotemporal regions. This method provided means to discriminate patient groups also at early disease stages.
Teune et al., 2010

5. HYPOMETABOLISM IN ND neuronal dysfunction neuronal dysconnection
neuronal death
amyloid burden
tau
neurotransmission dysfunction
immunitary system?

7. PIB in vivo vs post mortem FDG-PET
Longitudinal evaluation in the first patient studied with PIB Kadir A., Brain. 2011
MMSE 21 13
PIB in vivo
MMSE:
PIB in vivo vs post mortem
FDG-PET

8. Higher PIB retention was observed in MCI ApoE ε4 carriers compared to non-ApoE ε4 carriers (p < 0.005)
67% of the PIB+ MCI converted to AD at 28 ± 15 m follow-up
PIB+ MCI patients progressed to AD at an estimated rate of 25% per year
Nordberg A, 2013

9. 22% of HCs had PIB binding ranging from stages A to C
stages of amyloid A deposition in the human brain as proposed by Braak and Braak (1997)

10. Cross-sectional and Longitudinal Analysis of the Relationship Between Aβ Deposition, Cortical Thickness, and Memory in Cognitively Unimpaired Individuals and in Alzheimer Disease
JAMA Neurol. 2013;70(7): doi: /jamaneurol
Gray matter loss over 36 months was more extensive, especially in the temporal, precuneus and posterior cingulate gyrus, and occipital cortices, in the NC+ group compared with the NC− group.
Faster rates of gray matter loss were observed in the hippocampal regions. INF indicates inferior; LAT, lateral; LT, left; MED, medial; RT, right; and SUP, superior.

11. [(18)F]FDDNP:amyloid and Tau
Prediction of Cognitive Decline by Positron Emission Tomography of Brain Amyloid and Tau
[(18)F]FDDNP:amyloid and Tau
Best prediction?
Small et al., Arch Neurol. 2012

12. Brain inflammation: [11C](R)-PK11195 PET studies
Low level of PBR
High level of PBR
In vitro
Resting
Activated
In vivo
Microglia activation
Expression of peripheral benzodiazepine receptors (PBBS)
In vivo measurement using the PBR ligand [C-11]PK11195

13. PD
LBD
Iannaccone et al. submitted

14. Microglial activation and amyloid deposition in mild cognitive impairment. A Okello Neurology 2009
Our findings indicate that, while amyloid deposition and microglial activation can be detected in vivo in around 50% of patients with mild cognitive impairment (MCI), these pathologies can occur independently.

15. HYPOMETABOLISM IN ND neuronal dysfunction neuronal dysconnection
neuronal death
amyloid burden
tau
neurotransmission dysfunction
immunitary system?

16. The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET activation studies. Magistretti et al., Mol Psychiatry. 1996

17. Walburg effect in brain: when glucose metabolism exceeds that used for oxidative phosphorylation despite sufficient oxygen to metabolize glucose to carbon dioxide and water, it has traditionally been referred to as aerobic glycolysis.

19. In vivo Imaging: what , who, where, when, .........why
Small et al. Lancet Neurol. 2008