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Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study.
Lancet Neurol. 2012 Aug; 11(8):669-78.LN

Abstract

BACKGROUND

Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-β pathology measured at autopsy. However, these studies were small and not designed to prospectively measure sensitivity or specificity of amyloid PET imaging against a reference standard. We therefore prospectively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy.

METHODS

This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment. Participants had autopsy within 2 years of PET imaging with florbetapir ((18)F). For one of the primary analyses, the interpretation of the florbetapir scans (majority interpretation of five nuclear medicine physicians, who classified each scan as amyloid positive or amyloid negative) was compared with amyloid pathology (assessed according to the Consortium to Establish a Registry for Alzheimer's Disease standards, and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques); correlation of the image analysis results with amyloid burden was tested as a coprimary endpoint. Correlation, sensitivity, and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints. The study is registered with ClinicalTrials.gov, number NCT 01447719 (original study NCT 00857415).

FINDINGS

We included 59 participants (aged 47-103 years; cognitive status ranging from normal to advanced dementia). The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92% (36 of 39; 95% CI 78-98) and 100% (20 of 20; 80-100%), respectively, in people who had autopsy within 2 years of PET imaging, and 96% (27 of 28; 80-100%) and 100% (18 of 18; 78-100%), respectively, for those who had autopsy within 1 year. Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years (Spearman ρ=0·76; p<0·0001) and within 12 months between imaging and autopsy (0·79; p<0·0001).

INTERPRETATION

The results of this study validate the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. Additional research is needed to understand the prognostic implications of moderate to frequent plaque density.

FUNDING

Avid Radiopharmaceuticals.

Authors+Show Affiliations

Avid Radiopharmaceuticals, Philadelphia, PA, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22749065

Citation

Clark, Christopher M., et al. "Cerebral PET With Florbetapir Compared With Neuropathology at Autopsy for Detection of Neuritic Amyloid-β Plaques: a Prospective Cohort Study." The Lancet. Neurology, vol. 11, no. 8, 2012, pp. 669-78.
Clark CM, Pontecorvo MJ, Beach TG, et al. Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. Lancet Neurol. 2012;11(8):669-78.
Clark, C. M., Pontecorvo, M. J., Beach, T. G., Bedell, B. J., Coleman, R. E., Doraiswamy, P. M., Fleisher, A. S., Reiman, E. M., Sabbagh, M. N., Sadowsky, C. H., Schneider, J. A., Arora, A., Carpenter, A. P., Flitter, M. L., Joshi, A. D., Krautkramer, M. J., Lu, M., Mintun, M. A., & Skovronsky, D. M. (2012). Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. The Lancet. Neurology, 11(8), 669-78.
Clark CM, et al. Cerebral PET With Florbetapir Compared With Neuropathology at Autopsy for Detection of Neuritic Amyloid-β Plaques: a Prospective Cohort Study. Lancet Neurol. 2012;11(8):669-78. PubMed PMID: 22749065.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cerebral PET with florbetapir compared with neuropathology at autopsy for detection of neuritic amyloid-β plaques: a prospective cohort study. AU - Clark,Christopher M, AU - Pontecorvo,Michael J, AU - Beach,Thomas G, AU - Bedell,Barry J, AU - Coleman,R Edward, AU - Doraiswamy,P Murali, AU - Fleisher,Adam S, AU - Reiman,Eric M, AU - Sabbagh,Marwan N, AU - Sadowsky,Carl H, AU - Schneider,Julie A, AU - Arora,Anupa, AU - Carpenter,Alan P, AU - Flitter,Matthew L, AU - Joshi,Abhinay D, AU - Krautkramer,Michael J, AU - Lu,Ming, AU - Mintun,Mark A, AU - Skovronsky,Daniel M, AU - ,, Y1 - 2012/06/28/ PY - 2012/7/4/entrez PY - 2012/7/4/pubmed PY - 2012/12/10/medline SP - 669 EP - 78 JF - The Lancet. Neurology JO - Lancet Neurol VL - 11 IS - 8 N2 - BACKGROUND: Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-β pathology measured at autopsy. However, these studies were small and not designed to prospectively measure sensitivity or specificity of amyloid PET imaging against a reference standard. We therefore prospectively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy. METHODS: This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment. Participants had autopsy within 2 years of PET imaging with florbetapir ((18)F). For one of the primary analyses, the interpretation of the florbetapir scans (majority interpretation of five nuclear medicine physicians, who classified each scan as amyloid positive or amyloid negative) was compared with amyloid pathology (assessed according to the Consortium to Establish a Registry for Alzheimer's Disease standards, and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques); correlation of the image analysis results with amyloid burden was tested as a coprimary endpoint. Correlation, sensitivity, and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints. The study is registered with ClinicalTrials.gov, number NCT 01447719 (original study NCT 00857415). FINDINGS: We included 59 participants (aged 47-103 years; cognitive status ranging from normal to advanced dementia). The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92% (36 of 39; 95% CI 78-98) and 100% (20 of 20; 80-100%), respectively, in people who had autopsy within 2 years of PET imaging, and 96% (27 of 28; 80-100%) and 100% (18 of 18; 78-100%), respectively, for those who had autopsy within 1 year. Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years (Spearman ρ=0·76; p<0·0001) and within 12 months between imaging and autopsy (0·79; p<0·0001). INTERPRETATION: The results of this study validate the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques. Additional research is needed to understand the prognostic implications of moderate to frequent plaque density. FUNDING: Avid Radiopharmaceuticals. SN - 1474-4465 UR - https://www.unboundmedicine.com/medline/citation/22749065/Cerebral_PET_with_florbetapir_compared_with_neuropathology_at_autopsy_for_detection_of_neuritic_amyloid_β_plaques:_a_prospective_cohort_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1474-4422(12)70142-4 DB - PRIME DP - Unbound Medicine ER -