Pathologie in vivo: Amyloid PET bij de ziekte van Alzheimer Ph

Pathologie in vivo: Amyloid PET bij de ziekte van Alzheimer Ph

Pathologie in vivo:
Amyloid PET bij de
ziekte van
Alzheimer
Ph.Scheltens
Amsterdam
Biomarkers for (Prodromal) AD
Abnormal
CSF Aβ42
Amyloid imaging
FDG-PET
MRI hippocampal
volume
CSF Tau
Cognitive performance
Function (ADL)
FDG-PET
MRI hippocampal
volume
Amyloid
imaging
CSF Aβ42
Cognitive performance
Function (ADL)
CSF Tau
Normal
Presymptomatic
Prodromal
Dementia
Aisen PS, Petersen RC, Donohue MC, et al. Alzheimers Dement. 2010;6:239-246.
Time
[11C]PIB: first human studies
•
•
•
•
16 patients mild AD
9 controls
60 minutes scans
300 MBq [11C]PIB
SUV 40-60: initial studies were only 60 minutes
Klunk et al, Annals of Neurology, 2004; 55:306-319
First dutch [11C] PIB images
Tolboom et al, J Nucl Med. 2009 Feb;50(2):191-7.
PIB-PET predictive in MCI?
Tolboom, J Nucl Med 2009
1,20
1,00
BP ND
0,80
0,60
AD
0,40
0,20
0,00
-0,20
Controls
Milde cognitive impairment
MCI: looks like 2 subgroups..
Repeated PIB-scan
Ossenkoppele, EJNMMI, 2012. March 23
control
1,2
mild cognitive impairment
AD
1
0,8
BPND
0,6
0,4
0,2
0
-0,2
-10
0
10
20
30
40
50
Tim e (m onths )
PIB-PET predicts AD
[11C]PIB – mild cognitive impairment
Baseline:
1,2
1
Global BP ND
0,8
0,6
0,4
3 yr follow-up
0,2
0
-0,2
-10
0
10
20
Time (months)
30
40
50
•
•
•
•
N= 154 (<70y) patients underwent [11C]PIB and [18F]FDG
Setting: tertiary referral clinic
“forced to formulate one clinical diagnosis + indicate confidence”
5 clinicians with variable levels of experience and ‘confidence’ in PET
• [11C]PIB positive in:
–
–
–
–
40/66 (61%) patients with a clinical diagnosis AD
5/18 (28%) patients with clinical diagnosis FTD
4/5 (80%) patients with clinical diagnosis DLB
3/10 (30%) patients with other dementias
• PET results led to a change in diagnosis in 35 (23%)
patients.
• This only occurred when prior diagnostic certainty < 90%.
• Diagnostic confidence increased from 71±17% before to
87±16% after PET (p<0·001)
Coming soon……….
• [18F] Flutemetamol (FDA, 2013)
• [18F] Florbetapir (Amyvid) (FDA +EMA 2013)
• [18F] Florbetaben (submitted)
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TAU imaging
Future of diagnosis
Combination of markers  accurate + early diagnosis
Abnormal
FDG-PET
MRI hippocampal
volume
Amyloid
imaging
CSF Aβ42
Cognitive performance
Function (ADL)
CSF Tau
Normal
Preclinical
Prodromal
Clinical
criteria
Dementia
allow diagnosis
Time
Future of diagnosis
Combination of markers  accurate + early diagnosis
Abnormal
FDG-PET
MRI hippocampal
volume
Amyloid
imaging
CSF Aβ42
Cognitive performance
Function (ADL)
CSF Tau
Normal
Preclinical
Biomarkers
Prodromal
allow diagnosis
Dementia
Time
Future of diagnosis
Combination of markers  accurate + early diagnosis
Abnormal
FDG-PET
MRI hippocampal
volume
Amyloid
imaging
CSF Aβ42
Cognitive performance
Function (ADL)
CSF Tau
Normal
Biomarkers
predict diagnosis
Preclinical
Prodromal
Dementia
Time
Diagnostic role for amyloid imaging
• Discriminate underlying pathology: amyloid vs. non-amyloid
• Especially in young age-at-onset
– Atypical presentation
– No evident MRI abnormalities
– Less likely to have “age-related” amyloid
• Accurate diagnosis has implications
– Prognosis, heritability, symptomatic tx
– Prerequisite for developing disease-specific tx
– Selection for clinical trials
Twintig jaar achter bij oncologie
Dam opwerpen tegen dementie
Zorg beheersbaar houden
Minder groei aantal patiënten
 één nationale aanpak
DB
 voor patiënt van VANDAAG (zorg en ondersteuning) én
voor patiënt van MORGEN (preventie en genezing)
KERNWOORDEN
Sneller signaleren
Meer onderzoek doen naar en
inzicht verwerven in dementie
Bestaande kennis en
mogelijkheden beter toepassen
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