Comparison of <sup>18</sup>F‐florbetaben quantification results using the standard Centiloid, MR‐based, and MR‐less CapAIBL<sup>®</sup> approaches: Validation against histopathology

Doré, Vincent; Bullich, Santiago; Rowe, Christopher C.; Bourgeat, Pierrick; Konate, Salamata; Sabri, Osama; Stephens, Andrew; Barthel, Henryk; Fripp, Jürgen; Masters, Colin L.; Dinkelborg, Ludger; Salvado, Olivier; Villemagne, Victor L.; Santi, Susan De

doi:10.1016/j.jalz.2019.02.005

Cited by 63 publications

(48 citation statements)

References 29 publications

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“…This is reasonably concordant with the findings of Navitsky and colleagues, who determined a threshold of 24.1 CL with florbetapir for CERAD amyloid plaque classification of moderate or frequent vs sparse or none, in 59 individuals [22]. This is also concordant with the Centiloid analysis by Dore and colleagues of a florbetaben phase III post-mortem study in 66 individuals, which yielded a threshold of 19 CL for the same categorisation [23]. These thresholds are higher than those identified by La Joie et al, who determined a threshold of 12.2 CL for separating none or sparse plaques from moderate or frequent plaques; but oddly they found the same threshold for separating any plaques from no plaques in 179 individuals scanned with 11 C-PiB PET [21].…”

Section: Discussionsupporting

confidence: 89%

“…Three recent studies have examined the performance of amyloid PET CL thresholds compared with SoT neuropathology. These studies reported thresholds for detection of moderate or frequent neuritic plaque ranging from 12 to 24 CL but did not correct for time elapsed between amyloid scan and death and had relatively few cases with CL values close to the threshold values [21][22][23]. Only one compared to Alzheimer's disease neuropathologic change (ADNC) rating [1] or to expert visual read report of a positive scan [21].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease

et al. 2020

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Background: The Centiloid scale was developed to standardise the results of beta-amyloid (Aβ) PET. We aimed to determine the Centiloid unit (CL) thresholds for CERAD sparse and moderate-density neuritic plaques, Alzheimer's disease neuropathologic change (ADNC) score of intermediate or high probability of Alzheimer's Disease (AD), final clinicopathological diagnosis of AD, and expert visual read of a positive Aβ PET scan. Methods: Aβ PET results in CL for 49 subjects were compared with post-mortem findings, visual read, and final clinicopathological diagnosis. The Youden Index was used to determine the optimal CL thresholds from receiver operator characteristic (ROC) curves. Results: A threshold of 20.1 CL (21.3 CL when corrected for time to death, AUC 0.97) yielded highest accuracy in detecting moderate or frequent plaque density while < 10 CL was optimal for excluding neuritic plaque. The threshold for ADNC intermediate or high likelihood AD was 49.4 CL (AUC 0.98). Those cases with a final clinicopathological diagnosis of AD yielded a median CL result of 87.7 (IQR ± 42.2) with 94% > 45 CL. Positive visual read agreed highly with results > 26 CL. Conclusions: Centiloid values < 10 accurately reflected the absence of any neuritic plaque and > 20 CL indicated the presence of at least moderate plaque density, but approximately 50 CL or more best confirmed both neuropathological and clinicopathological diagnosis of Alzheimer's disease.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease

et al. 2020

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“…This is reasonably concordant with the findings of Navitsky and colleagues, who determined a threshold of 24.1 CL with florbetapir for CERAD amyloid plaque classification of moderate or frequent vs sparse or none, in 59 individuals [21]. This is also concordant with the Centiloid analysis by Dore and colleagues of a florbetaban phase III post-mortem study in 66 individuals, which yielded a threshold of 19 CL for the same categorisation [22]. These thresholds are higher than those identified by La Joie et al, who determined a threshold of 12.2 CL for separating none or sparse plaques from moderate or frequent plaques; and the same threshold of 12.2CL for separating any plaques from no plaques in 179 individuals scanned with 11 C-PiB PET [20].…”

Section: Fig 1 Centiloid Results and "High" Vs "Low" C Score Categoriessupporting

confidence: 89%

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s Disease

Amadoru

Doré

McLean

et al. 2019

Preprint

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Background: We aimed to determine the Centiloid unit (CL) thresholds for sparse and moderate density neuritic plaques. Methods: Amyloid PET results in CL for 49 subjects were compared with post-mortem neuritic plaque density, visual read, and final clinicopathological diagnosis. A Youden Index was used to determine the optimal CL thresholds from receiver operator characteristic (ROC) curves. Results: A threshold of 20.1 CL yielded highest accuracy in detecting moderate or frequent plaque density (ROC AUC 0.97). A threshold of 9.5 CL was optimal for detecting sparse, moderate or frequent plaques (ROC AUC 0.96). Those cases with a final clinicopathological diagnosis of Alzheimer’s disease yielded a median CL result of 87.7 (IQR ±42.2) with 94% > 45 CL. Positive visual read agreed highly with results >26 CL. Conclusions: In this cohort, values <9.5 CL accurately reflected the absence of any neuritic plaques, and >20.1 CL indicated the presence of at least moderate plaque density. Clinicopathological diagnosis of AD was rare with CL <45.

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“…An SUVR abnormality cutoff of 1.478 in a global cortical composite region relative to the cerebellar cortex was developed using histopathological confirmation as the standard of truth providing excellent sensitivity (89.4%) and specificity (92.3%) to detect established Aβ pathology [9]. Other groups have developed other SUVR abnormality cutoffs for 18 F-florbetaben PET ranging from 1.38 to 1.45 using different populations, analytical methods, and standards of truth [10,[12][13][14][15][16][17][18]. These SUVR cutoffs, however, were developed with the aim of discriminating between subjects with established Aβ pathology (e.g., AD) and other populations (e.g., cognitively normal elderly subjects).…”

Section: Introductionmentioning

confidence: 99%

Early detection of amyloid load using 18F-florbetaben PET

Bullich¹,

Roé-Vellvé²,

Marquié

et al. 2021

Alz Res Therapy

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Background A low amount and extent of Aβ deposition at early stages of Alzheimer’s disease (AD) may limit the use of previously developed pathology-proven composite SUVR cutoffs. This study aims to characterize the population with earliest abnormal Aβ accumulation using 18F-florbetaben PET. Quantitative thresholds for the early (SUVRearly) and established (SUVRestab) Aβ deposition were developed, and the topography of early Aβ deposition was assessed. Subsequently, Aβ accumulation over time, progression from mild cognitive impairment (MCI) to AD dementia, and tau deposition were assessed in subjects with early and established Aβ deposition. Methods The study population consisted of 686 subjects (n = 287 (cognitively normal healthy controls), n = 166 (subjects with subjective cognitive decline (SCD)), n = 129 (subjects with MCI), and n = 101 (subjects with AD dementia)). Three categories in the Aβ-deposition continuum were defined based on the developed SUVR cutoffs: Aβ-negative subjects, subjects with early Aβ deposition (“gray zone”), and subjects with established Aβ pathology. Results SUVR using the whole cerebellum as the reference region and centiloid (CL) cutoffs for early and established amyloid pathology were 1.10 (13.5 CL) and 1.24 (35.7 CL), respectively. Cingulate cortices and precuneus, frontal, and inferior lateral temporal cortices were the regions showing the initial pathological tracer retention. Subjects in the “gray zone” or with established Aβ pathology accumulated more amyloid over time than Aβ-negative subjects. After a 4-year clinical follow-up, none of the Aβ-negative or the gray zone subjects progressed to AD dementia while 91% of the MCI subjects with established Aβ pathology progressed. Tau deposition was infrequent in those subjects without established Aβ pathology. Conclusions This study supports the utility of using two cutoffs for amyloid PET abnormality defining a “gray zone”: a lower cutoff of 13.5 CL indicating emerging Aβ pathology and a higher cutoff of 35.7 CL where amyloid burden levels correspond to established neuropathology findings. These cutoffs define a subset of subjects characterized by pre-AD dementia levels of amyloid burden that precede other biomarkers such as tau deposition or clinical symptoms and accelerated amyloid accumulation. The determination of different amyloid loads, particularly low amyloid levels, is useful in determining who will eventually progress to dementia. Quantitation of amyloid provides a sensitive measure in these low-load cases and may help to identify a group of subjects most likely to benefit from intervention. Trial registration Data used in this manuscript belong to clinical trials registered in ClinicalTrials.gov (NCT00928304, NCT00750282, NCT01138111, NCT02854033) and EudraCT (2014-000798-38).

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Comparison of ¹⁸F‐florbetaben quantification results using the standard Centiloid, MR‐based, and MR‐less CapAIBL^® approaches: Validation against histopathology

Cited by 63 publications

References 29 publications

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s Disease

Early detection of amyloid load using 18F-florbetaben PET

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Comparison of 18F‐florbetaben quantification results using the standard Centiloid, MR‐based, and MR‐less CapAIBL® approaches: Validation against histopathology

Cited by 63 publications

References 29 publications

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s disease

Comparison of amyloid PET measured in Centiloid units with neuropathological findings in Alzheimer’s Disease

Early detection of amyloid load using 18F-florbetaben PET

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Product

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About

Comparison of ¹⁸F‐florbetaben quantification results using the standard Centiloid, MR‐based, and MR‐less CapAIBL^® approaches: Validation against histopathology