Topographic staging of tau positron emission tomography images

Introduction: It has been proposed that the signal distribution on tau positron emission tomography (PET) images could be used to define pathologic stages similar to those seen in neuropathology. Methods: Three topographic staging schemes for tau PET, two sampling the temporal and occipital subregions only and one sampling cortical gray matter across the major brain lobes, were evaluated on flortaucipir F 18 PET images in a test-retest scenario and from Alzheimer's Disease Neuroimaging Initiative 2. Results: All three schemes estimated stages that were significantly associated with amyloid status and when dichotomized to tau positive or negative were 90% to 94% concordant in the populations identified. However, the schemes with fewer regions and simpler decision rules yielded more robust performance in terms of fewer unclassified scans and increased test-retest reproducibility of assigned stage. Discussion: Tau PET staging schemes could be useful tools to concisely index the regional involvement of tau pathology in living subjects. Simpler schemes may be more robust

Amyloid imaging and cognitive decline in nondemented oldest-old: the 90+ Study.

BackgroundThe goal of this study was to examine cross-sectional and longitudinal associations between cognitive performance and beta amyloid (Aβ) load determined by florbetapir F18 positron emission tomography (PET) in nondemented oldest-old.MethodsThirteen nondemented (normal or cognitively impaired nondemented) participants (median age, 94.2 years) from The 90+ Study underwent florbetapir-PET scanning within 3 months of baseline neuropsychological testing. Amyloid load was measured with a semi-automated quantitative analysis of average cortical-to-cerebellar standardized uptake value ratio (SUVr) and a visual interpretation (Aβ- or Aβ+). Neuropsychological testing was repeated every 6 months.ResultsAt baseline, SUVr correlated significantly with tests of global cognition and memory. During follow-up (median, 1.5 years), the Aβ+ group had steeper declines on most cognitive tests, particularly global cognitive measures.ConclusionThis preliminary study suggests that greater amyloid load is associated with poorer cognition and faster cognitive decline in nondemented oldest-old. Amyloid load may identify individuals at increased risk of developing Alzheimer's disease

Amyloid Imaging with Florbetapir-PET Correlates with Cognitive Performance in Non-Demented Oldest-Old

Volleyball meet results, scoresHead coach: Beth LauniereWomen's VolleyballUtah 3 (30, 32, 30, 30); UNLV 1 (16, 34, 28, 23)Volleyball Box Score Utah Volleyball #18 Utah Utes vs UNLV (09-21-06 at Las Vegas, Nev.) Attack E TA Serve Ast SA SE RE Block Dig BS BA BE BHE ## Utah Utes S K 2 5 8 11 15 17 12 14 16 18 ANDERSON, Sydney BAIRD, Lori LOVELL, Kathryn SALVO, Airial TOONE, Emillie WEBB, Whitney KRUG, Shannon DANGERFIELD, Connie ROBISON, Kate LAVARIAS, Lacey 3 4 4 4 4 4 2 4 4 1 1 12 13 17 10 8 0 0 1 0 1 2 6 4 2 5 0 0 0 0 7 26 32 55 23 23 1 0 5 0 .000 .385 .219 .236 .348 .130 .000 .000 .200 .000 33 0 1 1 0 1 20 0 1 0 0 0 0 2 0 0 0 1 1 0 1 3 0 2 0 2 1 2 2 0 0 0 1 0 1 0 0 0 0 0 11 3 5 21 1 11 7 11 8 1 0 0 0 0 0 0 0 0 0 0 2 7 2 3 8 7 2 0 0 0 0 0 4 0 0 1 0 0 0 0 1 0 0 0 0 0 0 0 1 0 - Totals 4 62 20 172 .244 57 4 13 2 79 0 31 5 2 - Team Attack By Set Set K E TA Pct 1 16 2 38 .368 2 20 7 53 .245 3 12 8 43 .093 4 14 3 38 .289 Pts TOTAL TEAM BLOCKS: 15.5 SET SCORES Utah Utes (3) UNLV (1) Attack E TA ## UNLV S K 2 3 6 10 15 18 4 5 7 8 9 14 LUMSDEN, Brittani NUA, Melody ALADJOVA, Maria MIRAMONTES, Lauren WALTERS, Jessica GREENWOOD, Erin CUNNINGHAM, Camille KOOCHI, Kristin WALKER, Jada BANKS, Michelle NOLAND, Samantha JOHNSON, Jennifer Team 4 4 4 3 4 4 4 4 4 1 3 4 13 0 20 1 15 5 0 0 0 2 0 7 10 1 9 0 8 2 1 0 0 1 2 3 51 2 52 7 41 17 1 0 0 8 5 17 Totals 4 63 37 201 Team Attack By Set Set K E TA Pct 1 9 12 50 -.060 2 23 3 55 .364 3 15 11 46 .087 4 16 11 50 .100 Pct 1 Pct .059 4 Team Records: 30 32 30 30 16 34 28 23 2 3 10-2, 3-0 MWC 9-4, 1-1 MWC Serve Ast SA SE RE Block Dig BS BA BE BHE Pts .235 1 32 1 0 1 0 2 20 1 0 0 2 0 0 1 0 0 0 0 1 0 0 0 0 1 1 1 0 0 1 1 2 0 0 0 0 1 0 1 0 1 0 0 0 0 0 0 0 1 9 11 15 1 4 6 11 9 18 0 1 0 0 0 1 0 0 0 0 0 0 0 0 0 1 0 1 1 2 4 0 0 0 0 4 3 0 0 0 0 0 1 0 0 0 1 1 0 0 2 1 0 0 0 0 0 0 0 0 3 - .129 60 2 7 4 85 1 16 3 6 - -.500 .212 .143 .171 .176 -1.000 .000 .000 .125 -.400 TOTAL TEAM BLOCKS: 9.0 Site: Las Vegas, Nev. (Cox Pavilion) Date: 09-21-06 Attend: 224 Time: 2:06 Referees: Patsy Malta, Moose Knudtso

Comparing positron emission tomography imaging and cerebrospinal fluid measurements of β-amyloid

ObjectiveWe examined agreement and disagreement between 2 biomarkers of β-amyloid (Aβ) deposition (amyloid positron emission tomography [PET] and cerebrospinal fluid [CSF] Aβ1-42 ) in normal aging and dementia in a large multicenter study.MethodsConcurrently acquired florbetapir PET and CSF Aβ were measured in cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease participants (n = 374) from the Alzheimer's Disease Neuroimaging Initiative. We also compared Aβ measurements in a separate group with serial CSF measurements over 3.1 ± 0.8 years that preceded a single florbetapir session. Additional biomarker and cognitive data allowed us to further examine profiles of discordant cases.ResultsFlorbetapir and CSF Aβ were inversely correlated across all diagnostic groups, and dichotomous measurements were in agreement in 86% of subjects. Among subjects showing the most disagreement, the 2 discordant groups had different profiles: the florbetapir(+) /CSF Aβ(-) group was larger (n = 13) and was made up of only normal and early MCI subjects, whereas the florbetapir(-) /CSF Aβ(+) group was smaller (n = 7) and had poorer cognitive function and higher CSF tau, but no ApoE4 carriers. In the longitudinal sample, we observed both stable longitudinal CSF Aβ trajectories and those actively transitioning from normal to abnormal, but the final CSF Aβ measurements were in good agreement with florbetapir cortical retention.InterpretationCSF and amyloid PET measurements of Aβ were consistent in the majority of subjects in the cross-sectional and longitudinal populations. Based on our analysis of discordant subjects, the available evidence did not show that CSF Aβ regularly becomes abnormal prior to fibrillar Aβ accumulation early in the course of disease

Amyloid deposition, hypometabolism, and longitudinal cognitive decline

Objective: Using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) population, we examined (1) cross‐sectional relationships between amyloid deposition, hypometabolism, and cognition, and (2) associations between amyloid and hypometabolism measurements and longitudinal cognitive measurements. Methods: We examined associations between mean cortical florbetapir uptake, mean 18 F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) within a set of predefined regions, and Alzhiemer's Disease Assessment Scale (ADAS‐cog) performance in 426 ADNI participants (126 normal, 162 early mild cognitive impairment [EMCI], 85 late MCI [LMCI], 53 Alzheimer disease [AD] patients). For a subset of these (76 normal, 81 LMCI) we determined whether florbetapir and FDG‐PET were associated with retrospective decline in longitudinal ADAS‐cog measurements. Results: Twenty‐nine percent of normal subjects, 43% of EMCI patients, 62% of LMCI patients, and 77% of AD patients were categorized as florbetapir positive. Florbetapir was negatively associated with concurrent FDG and ADAS‐cog in both MCI groups. In longitudinal analyses, florbetapir‐positive subjects in both normal and LMCI groups had greater ongoing ADAS‐cog decline than those who were florbetapir negative. However, in normal subjects, florbetapir positivity was associated with greater ADAS‐cog decline than FDG, whereas in LMCI, FDG positivity was associated with greater decline than florbetapir. Interpretation: Although both hypometabolism and β‐amyloid (Aβ) deposition are detectable in normal subjects and all diagnostic groups, Aβ showed greater associations with cognitive decline in normal participants. In view of the minimal cognitive deterioration overall in this group, this suggests that amyloid deposition has an early and subclinical impact on cognition that precedes metabolic changes. At moderate and later stages of disease (LMCI/AD), hypometabolism becomes more pronounced and more closely linked to ongoing cognitive decline. ANN NEUROL 2012;72:578–586Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94245/1/23650_ftp.pd

PET imaging of amyloid with Florbetapir F 18 and PET imaging of dopamine degeneration with \u3csup\u3e18\u3c/sup\u3eF-AV-133 (florbenazine) in patients with Alzheimer\u27s disease and Lewy body disorders

Background: Biomarkers based on the underlying pathology of Alzheimer\u27s disease (AD) and Dementia with Lewy Bodies (DLB) have the potential to improve diagnosis and understanding of the substrate for cognitive impairment in these disorders. The objective of this study was to compare the patterns of amyloid and dopamine PET imaging in patients with AD, DLB and Parkinson\u27s disease (PD) using the amyloid imaging agent florbetapir F 18 and 18F-AV-133 (florbenazine), a marker for vesicular monamine type 2 transporters (VMAT2).Methods: Patients with DLB and AD, Parkinson\u27s disease (PD) and healthy controls (HC) were recruited for this study. On separate days, subjects received intravenous injections of florbetapir, and florbenazine. Amyloid burden and VMAT2 density were assessed quantitatively and by binary clinical interpretation. Imaging results for both tracers were compared across the four individual diagnostic groups and for combined groups based on underlying pathology (AD/DLB vs. PD/HC for amyloid burden and PD/DLB vs. AD/HC for VMAT binding) and correlated with measures of cognition and parkinsonism.Results: 11 DLB, 10 AD, 5 PD, and 5 controls participated in the study. Amyloid binding was significantly higher in the combined AD/DLB patient group (n = 21) compared to the PD/HC groups (n = 10, mean SUVr: 1.42 vs. 1.07; p = 0.0006). VMAT2 density was significantly lower in the PD/DLB group (n = 16) compared to the AD/ HC group (n = 15; 1.83 vs. 2.97; p \u3c 0.0001). Within the DLB group, there was a significant correlation between cognitive performance and striatal florbenazine binding (r = 0.73; p = 0.011).Conclusions: The results of this study show significant differences in both florbetapir and florbenazine imaging that are consistent with expected pathology. In addition, VMAT density correlated significantly with cognitive impairment in DLB patients (ClinicalTrials.gov identifier: NCT00857506, registered March 5, 2009). © 2014 Siderowf et al.; licensee BioMed Central Ltd

Amyloid imaging and cognitive decline in nondemented oldest-old: The 90+ Study

BACKGROUND: The goal of this study was to examine cross-sectional and longitudinal associations between cognitive performance and beta amyloid (Aβ) load determined by florbetapir F18 positron emission tomography (PET) in non-demented oldest-old. METHODS: Thirteen non-demented (normal or cognitively impaired non-demented) participants (median age=94.2 years) from The 90+ Study underwent florbetapir-PET scanning within 3 months of baseline neuropsychological testing. Amyloid load was measured with a semiautomated quantitative analysis of average cortical to cerebellar standard uptake values (SUVr) ratio and a visual interpretation (Aβ- or Aβ+). Neuropsychological testing was repeated every 6 months. RESULTS: At baseline, SUVr correlated significantly with tests of global cognition and memory. During follow-up (median=1.5 years), the Aβ+ group had steeper declines on most cognitive tests, particularly global cognitive measures. CONCLUSION: This preliminary study suggests that greater amyloid load is associated with poorer cognition and faster cognitive decline in non-demented oldest-old. Amyloid load may identify individuals at increased risk of developing Alzheimer's disease