Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load
Leuzy, Antoine LU ; Lilja, Johan LU ; Buckley, Christopher J. ; Ossenkoppele, Rik LU ; Palmqvist, Sebastian LU
; Battle, Mark
LU
; Farrar, Gill
; Thal, Dietmar R.
; Janelidze, Shorena
LU
and Stomrud, Erik
LU
, et al.
(2020)
In Neurology
95(21).
p.2834-2844
- Abstract
OBJECTIVE: To evaluate a novel β-amyloid (Aβ)-PET-based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ42/Aβ40, and post-mortem neuritic plaque burden as standards of truth. METHODS: One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with Aβ-PET: Swedish BioFINDER, n = 392, [18F]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [18F]florbetapir; and a phase 3 end-of-life study, n = 100, [18F]flutemetamol. The relationships between Aβ index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed. The diagnostic... (More)
OBJECTIVE: To evaluate a novel β-amyloid (Aβ)-PET-based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ42/Aβ40, and post-mortem neuritic plaque burden as standards of truth. METHODS: One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with Aβ-PET: Swedish BioFINDER, n = 392, [18F]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [18F]florbetapir; and a phase 3 end-of-life study, n = 100, [18F]flutemetamol. The relationships between Aβ index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed. The diagnostic performances of Aβ index and SUVR were compared with visual reads, CSF Aβ42/Aβ40, and Aβ histopathology used as reference standards. RESULTS: Strong associations were observed between Aβ index and SUVR (R2: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating Aβ-positive from Aβ-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF Aβ42/Aβ40, and AUCs of 0.820 to 0.823 to detect abnormal Aβ histopathology. Both measures also showed a similar distribution across postmortem-based Aβ phases (based on anti-Aβ 4G8 antibodies). Compared to models using visual read alone, the addition of the Aβ index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal Aβ histopathology. CONCLUSION: The proposed Aβ index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. Aβ index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different Aβ-PET tracers. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the Aβ accumulation index accurately differentiates Aβ-positive from Aβ-negative participants compared to Aβ-PET visual reads, CSF Aβ42/Aβ40, and Aβ histopathology.
(Less)
- author
- Leuzy, Antoine
LU
; Lilja, Johan
LU
; Buckley, Christopher J.
; Ossenkoppele, Rik
LU
; Palmqvist, Sebastian
LU
; Battle, Mark
LU
; Farrar, Gill
; Thal, Dietmar R.
; Janelidze, Shorena
LU
and Stomrud, Erik
LU
, et al. (More)
- Leuzy, Antoine
LU
; Lilja, Johan
LU
; Buckley, Christopher J.
; Ossenkoppele, Rik
LU
; Palmqvist, Sebastian
LU
; Battle, Mark
LU
; Farrar, Gill
; Thal, Dietmar R.
; Janelidze, Shorena
LU
; Stomrud, Erik
LU
; Strandberg, Olof
LU
; Smith, Ruben
LU
and Hansson, Oskar
LU
(Less)
- organization
- publishing date
- 2020
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Neurology
- volume
- 95
- issue
- 21
- pages
- 2834 - 2844
- publisher
- Lippincott Williams & Wilkins
- external identifiers
-
- scopus:85096815753
- pmid:33077542
- ISSN
- 1526-632X
- DOI
- 10.1212/WNL.0000000000011031
- language
- English
- LU publication?
- yes
- id
- ff2f2713-59b7-465e-a3d9-c60e7800a7c0
- date added to LUP
- 2021-03-18 16:17:14
- date last changed
- 2024-05-02 05:15:12
@article{ff2f2713-59b7-465e-a3d9-c60e7800a7c0,
abstract = {{<p>OBJECTIVE: To evaluate a novel β-amyloid (Aβ)-PET-based quantitative measure (Aβ accumulation index [Aβ index]), including the assessment of its ability to discriminate between participants based on Aβ status using visual read, CSF Aβ42/Aβ40, and post-mortem neuritic plaque burden as standards of truth. METHODS: One thousand one hundred twenty-one participants (with and without cognitive impairment) were scanned with Aβ-PET: Swedish BioFINDER, n = 392, [18F]flutemetamol; Alzheimer's Disease Neuroimaging Initiative (ADNI), n = 692, [18F]florbetapir; and a phase 3 end-of-life study, n = 100, [18F]flutemetamol. The relationships between Aβ index and standardized uptake values ratios (SUVR) from Aβ-PET were assessed. The diagnostic performances of Aβ index and SUVR were compared with visual reads, CSF Aβ42/Aβ40, and Aβ histopathology used as reference standards. RESULTS: Strong associations were observed between Aβ index and SUVR (R2: BioFINDER 0.951, ADNI 0.943, end-of-life, 0.916). Both measures performed equally well in differentiating Aβ-positive from Aβ-negative participants, with areas under the curve (AUCs) of 0.979 to 0.991 to detect abnormal visual reads, AUCs of 0.961 to 0.966 to detect abnormal CSF Aβ42/Aβ40, and AUCs of 0.820 to 0.823 to detect abnormal Aβ histopathology. Both measures also showed a similar distribution across postmortem-based Aβ phases (based on anti-Aβ 4G8 antibodies). Compared to models using visual read alone, the addition of the Aβ index resulted in a significant increase in AUC and a decrease in Akaike information criterion to detect abnormal Aβ histopathology. CONCLUSION: The proposed Aβ index showed a tight association to SUVR and carries an advantage over the latter in that it does not require the definition of regions of interest or the use of MRI. Aβ index may thus prove simpler to implement in clinical settings and may also facilitate the comparison of findings using different Aβ-PET tracers. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that the Aβ accumulation index accurately differentiates Aβ-positive from Aβ-negative participants compared to Aβ-PET visual reads, CSF Aβ42/Aβ40, and Aβ histopathology.</p>}},
author = {{Leuzy, Antoine and Lilja, Johan and Buckley, Christopher J. and Ossenkoppele, Rik and Palmqvist, Sebastian and Battle, Mark and Farrar, Gill and Thal, Dietmar R. and Janelidze, Shorena and Stomrud, Erik and Strandberg, Olof and Smith, Ruben and Hansson, Oskar}},
issn = {{1526-632X}},
language = {{eng}},
number = {{21}},
pages = {{2834--2844}},
publisher = {{Lippincott Williams & Wilkins}},
series = {{Neurology}},
title = {{Derivation and utility of an Aβ-PET pathology accumulation index to estimate Aβ load}},
url = {{http://dx.doi.org/10.1212/WNL.0000000000011031}},
doi = {{10.1212/WNL.0000000000011031}},
volume = {{95}},
year = {{2020}},
}