ADNI PET CORE Boston April 27 Bill Jagust, Suzanne Baker, Bob Koeppe, Eric Reiman, Kewei Chen, Chet Mathis, Julie Price
ADNI Florbetapir scan counts Number of Florbetapir scans N SMC EMCI LMCI AD Total 265 4 32 223 98 93 2 25 77 29 53 5 75 3 27 5 72 7 322 4 7 3 7 8 248 ADNI AV45 scan counts Number of AV45 scans N SMC EMCI LMCI AD Total 34 23 22 2 3 2 3 4 2 2
Amyloid Imaging Followup N=7 New (N=3) Florbetapir or Florbetaben Every 2 Years Florbetapir or Florbetaben Tau Imaging 8% of Amyloid Positive 2% of Amyloid Negative All (N=) [ 8 F]AV45 3 additional scans over 4 years [ 8 F]AV45 [ 8 F]AV45 [ 8 F]AV45 2% of Amyloid Positive 8% of Amyloid Negative FDG Imaging MCI/AD (N~65) FDG additional scan at 4 years [ 8 F]AV45
Baseline Florbetapir Distribution 3% are Florbetapir+ Normal N= 264 36% are Florbetapir+ SMC N=4 Frequency 48% are Florbetapir+ 67% are Florbetapir+ EMCI N=33 LMCI N=224 86% are Florbetapir+ AD N=93 Baseline florbetapir cortical SUVR
Florbetapir annual change Florbetapir rate of change >2 florbetapir scans 3 florbetapir scans Baseline florbetapir SUVR (composite ref region) Baseline florbetapir SUVR (composite ref region)
Florbetapir trajectories by diagnosis 3 florbetapir scans (N=322) 4 florbetapir scans (N=8).2. Florbetapir Cortical SUVR (composite reference region)..8.2..8.2..8.2..8.2..8 N SMC EMCI LMCI AD Florbetapir Cortical SUVR (composite reference region)..9.8.7...9.8.7...9.8.7...9.8.7 N EMCI LMCI AD 6 7 8 9 Age 7 8 9 Age
Florbetapir change in amyloid-negaive normals Florbetapir SUVR Accumulators (slope>) Early AccumulaIon Regions CorIcal Summary Regions Non-accumulators Florbetapir SUVR Age
Episodic memory NegaIve normal accumulators are more likely to experience cogniive decline Accumulators Early AccumulaIon Regions CorIcal Summary Regions Episodic memory p=.2 Non-accumulators Years relaive to baseline florbetapir
AV45 PET SUVR quantification Medial temporal Inferolateral temporal NeocorIcal Braak staging approach Braak I/II Braak III/IV Braak V/VI Schwarz et al. Brain 26, Schöll, Lockhart, et al. Neuron 26; Maass et al. in revision
ADNI AV45 PET summary Braak Staging AV45 Braak /2 (PVC) 3. 2.5 2..5 Medial temporal Inferolateral temporal NeocorIcal N= Amyloid - Amyloid + AV45 Braak 3/4 (PVC) 3. 2.5 2..5 AV45 Braak 5/6 (PVC) 3. 2.5 2..5... N SMC EMCI LMCI AD DX Group N SMC EMCI LMCI AD DX Group N SMC EMCI LMCI AD DX Group Whole brain average AV45 Braak All (PVC) 3. 2.5 2..5 Amyloid - Amyloid +. N SMC EMCI LMCI AD DX Group
ADNI AV45 summary NeocorIcal 3. RID 452 74 yo APOE4+ male Recently converted from MCI MMSE=4 ADAS-cog=37 Florbetapir SUVR =.6 AV45 Braak 5/6 (PVC) 2.5 2..5. N SMC EMCI LMCI AD DX Group RID 4765 8yo APOE4+ male Recently converted from EMCI MMSE=2 ADAS-cog=9 Florbetapir SUVR =.32
AV45 tau and cognitive performance Medial temporal Inferolateral temporal NeocorIcal ADAS-cog 3 2 Florbetapir+ Florbetapir- InteracIon p=.5 ADAS-cog 3 2 p=. ADAS-cog 3 2 p=.5..3.5.7 AV45 Braak 2..25.5.75 AV45 Braak 34..2.4.6.8 AV45 Braak 56
AV45 comparison in 2 samples Maass et al. in revision
U Penn CSF Elecsys and AV45 N=49 (22 N/SMC, 2 MCI, 6 AD) with AV45-PET and CSF measurements within.5yrs CSF elecsys tau 7 6 5 4 3 CSF tau CSF elecsys ptau 4 CSF ptau CSF elecsys abeta 2 9 CSF Aβ42 R 2 =.2 R 2 =.23 R 2 =.28 5 6 Amyloid - Amyloid + 2 2 6..5 2. 2.5 AV45 Braak /2..5 2. 2.5 AV45 Braak /2 3..5 2. 2.5 AV45 Braak /2 7 6 CSF tau CSF ptau 5 6 CSF Aβ42 R 2 =.2 R 2 =.4 R 2 =.6 CSF elecsys tau 5 4 3 CSF elecsys ptau 4 CSF elecsys abeta 2 9 2 2 6..5 2. 2.5 3. AV45 Braak 3/4..5 2. 2.5 3. AV45 Braak 3/4 3..5 2. 2.5 3. AV45 Braak 3/4
U Penn CSF AlzBio3 and AV45 N=24 ( N, MCI, 3 AD) with AV45-PET and CSF measurements within 3 yrs 25 2 CSF tau 2 5 CSF ptau R 2 =.28 R 2 =.9 Amyloid - Amyloid + 25 CSF Aβ R 2 =.49 CSF AlzBio3 tau 5 CSF AlzBio3 ptau CSF AlzBio3 abeta 2 5 5 5..5 2. 2.5 AV45 Braak /2..5 2. 2.5 AV45 Braak /2..5 2. 2.5 AV45 Braak /2 25 CSF tau 2 CSF ptau R 2 =.2 R 2 =.3 25 CSF Aβ R 2 =.29 2 5 CSF AlzBio3 tau 5 CSF AlzBio3 ptau CSF AlzBio3 abeta 2 5 5 5..5 2. 2.5 3. AV45 Braak 3/4..5 2. 2.5 3. AV45 Braak 3/4..5 2. 2.5 3. AV45 Braak 3/4
Recent AV45-CSF tau studies Harvard Aging Brain Study N=3 Normals Wash U N=4 Normal, Impaired Chhatwal et al. Neurology 26 Gordon et al. Brain 26
Upcoming PET Core work Pipeline for florbetaben +/- categorization for ADNI3 tau scanning schedule AV45 quantification methods Cross-sectional and longitudinal relationships between florbetapir, AV45, CSF, cognition
Thank you
CSF Elecsys and AV45 N=49 (22 N/SMC, 2 MCI, 6 AD) with AV45-PET and CSF measurements within.5yrs 3 R 2 =.45.3 Amyloid - Amyloid + R 2 =.45 R 2 =.28 5 CSF Elecsys tau/abeta 2 CSF Elecsys ptau/abeta.2. CSF elecsys abeta 2 9 6..5 2. 2.5 AV45 Braak /2...5 2. 2.5 AV45 Braak /2 3..5 2. 2.5 AV45 Braak /2 3 R 2 =.24 R 2 =.24 R 2 =.6.3 5 CSF Elecsys tau/abeta 2 CSF Elecsys ptau/abeta.2. CSF elecsys abeta 2 9 6..5 2. 2.5 3. AV45 Braak 3/4...5 2. 2.5 3. AV45 Braak 3/4 3..5 2. 2.5 3. AV45 Braak 3/4
Tau, neurodegeneration & cognitive change Entorhinal/hippocampal Braak I/II FDG Hippocampal volume ADAS-cog change 6 4 2 Florbetapir+ Florbeatpir- InteracIon p=. ADAS-cog change 6 4 2 ADAS2.pdf InteracIon p=.2 ADAS-cog change 6 4 2 InteracIon p=. -2-2 -2..5 2. 2.5 AV45 SUVR Braak2..2.3.4.5 FDG.3.4.5.6 Hippocampal Volume Post Cingulate Gyrus L Angular Gyrus L Inf Temporal Gyrus R Angular Gyrus R Inf Temporal Gyrus
Florbetapir+ only p<. Age Sex EducaIon ApoE4 + AV45 PET p=.3 FDG PET p=.2 Hippocampal Vol ADAS-cog Long ADAS-cog p=.9
-.55** Hippocampal volume -.96 ** Hipp/entorhinal AV45.32* (.75**) ADAS-cog Indirect effect:.29 [.9,.6]
Florbetapir annual change distribuion Baseline florbetapir- Baseline florbetapir+ 6% are APOE4+ 73% are APOE4+ Normal N= 28 4% are APOE4+ 92% are APOE4+ SMC N= 73 Frequency 7% are APOE4+ 7% are APOE4+ EMCI N= 28 38% are APOE4+ 66% are APOE4+ LMCI N= 49 % are APOE4+ 66% are APOE4+ AD N= 49 Annual florbetapir change (WM ref region) Total N= 697
>2 yr Florbetapir Trajectories Nonaccumulators Accumulators Baseline florbetapir - Baseline florbetapir + Florbetapir SUVR annual change 2..5. 2..5. 2..5. 2..5. 2..5. 6 7 8 9 6 7 8 9 Age 78% of Florbetapir+ are Accumulators 5% of Florbetapir- are Accumulators (5% convert to +) 76% of Florbetapir+ are Accumulators 59% of Florbetapir- are Accumulators (2% convert to +) 7% of Florbetapir+ are Accumulators 58% of Florbetapir- are Accumulators (5% convert to +) 67% of Florbetapir+ are Accumulators 58% of Florbetapir- are Accumulators (% convert to +) 68% of Florbetapir+ are Accumulators 44% of Florbetapir- are Accumulators (% convert to +) N SMC EMCI LMCI AD N= 28 N= 73 factor(av45_ N= 28 N= 49 N= 49 Total N= 697
>4 yr Florbetapir Trajectories Baseline florbetapir - Baseline florbetapir + 2. Nonaccumulators Accumulators 9% of Florbetapir+ are Accumulators Florbetapir SUVR annual change.5. 2..5. 2..5. 2..5. 56% of Florbetapir- are Accumulators (7% convert to +) 77% of Florbetapir+ are Accumulators 63% of Florbetapir- are Accumulators (23% convert to +) 76% of Florbetapir+ are Accumulators 58% of Florbetapir- are Accumulators (5% convert to +) 33% of Florbetapir+ are Accumulators 5% of Florbetapir- are Accumulators (% convert to +) 6 7 8 9 6 7 8 9 Age N EMCI LMCI AD N= 8 N= 9 factor(av45_nontp N= 44 N= 5 Total N= 29
ADNI FDG scan counts Number of FDG scans N SMC EMCI LMCI AD Total 343 6 36 49 24 48 2 258 67 279 2 86 3 92 8 75 349 4 85 62 58 35 5 72 46 28 6 39 5 44 7 25 56 8 8 5 28 33 9 5 5 Total 99 6 474 37 486 3359
A second (or third?) tau tracer in ADNI? Strong commitment to adding a second tau tracer to ADNI3 - As of today, no additional tracers available for summer 27 startup Requirements for a tau tracer Preclinical/clinical supportive data Regulatory pathway Manufacture at no cost to ADNI Distribution to a substantial proportion of sites