Contribution of Imaging to the future
understanding of loss of memory due
to neurodegeneration
Rosa Maria Moresco
University of Milan Bicocca
In vivo Imaging
Anatomy
Morphology
Connectivity
TAC, MRI,
Gray matter density
Fiber tracking DT-MRI
Knowledge
Function
Perfusion
Metabolism
PET, fMRI, TAC perf.
Technology
Molecules
Receptors
Enzymes
Proteins
PET SPET
Metodology
Brain glucose metabolism
Typical Alzheimer disease pattern
R
L
HSR Milano
Typical Cerebral
Metabolic Patterns
in Neurodegenerative
Disorders
Voxel-based analysis (SPM5)
96 patients
each group
vs. 18 HC
two sample t-test
Teune et al., 2010
R
HYPOMETABOLISM IN ND
neuronal dysfunction
neuronal dysconnection
neuronal death
amyloid burden
tau
neurotransmission dysfunction
immunitary system?
Longitudinal evaluation in the first patient studied with PIB Kadir A., Brain. 2011
MMSE
21
PIB in vivo
MMSE: 27
21
FDG-PET
13
13
PIB in vivo vs post mortem
Higher PIB retention
was observed in MCI
ApoE ε4 carriers
compared to nonApoE 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
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)
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):903-911. doi:10.1001/jamaneurol.2013.1062
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.
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
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
PD
Iannaccone et al. submitted
LBD
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.
HYPOMETABOLISM IN ND
neuronal dysfunction
neuronal dysconnection
neuronal death
amyloid burden
tau
neurotransmission dysfunction
immunitary system?
The contribution of astrocytes to the 18F-2-deoxyglucose signal in PET
activation studies. Magistretti et al., Mol Psychiatry. 1996
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.
In vivo Imaging: what , who, where, when, .........why
Small et al. Lancet Neurol. 2008