Abnormal Amyloid Load in Mild Cognitive Impairment: The Effect of Reducing the PiB-PET Threshold

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Abnormal Amyloid Load in Mild Cognitive Impairment : The Effect of Reducing the PiB-PET Threshold. / Ismail, Rola; Parbo, Peter; Hansen, Kim V.; Schaldemose, Jeppe L.; Dalby, Rikke B.; Tietze, Anna; Kjeldsen, Pernille L.; la Cour, Sanne Hage; Qvist, Per; Gottrup, Hanne; Eskildsen, Simon F.; Brooks, David J.

In: Journal of Neuroimaging, Vol. 29, No. 4, 01.07.2019, p. 499-505.

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@article{4f0c505f2b9141a1a19c22360cb3edc6,
title = "Abnormal Amyloid Load in Mild Cognitive Impairment: The Effect of Reducing the PiB-PET Threshold",
abstract = "BACKGROUND AND PURPOSE: In vivo detection of β-amyloid (Aβ) plaques in Alzheimer's disease (AD) is now possible with 11C-PiB positron emission tomography (PET). Conventionally, a cortical:cerebellar PiB uptake ratio threshold of 1.4-1.5 has been used to categorize at-risk subjects as “amyloid-positive” and “amyloid-negative.” It has been suggested that this threshold is too conservative and may miss early amyloid pathology. We investigated the relationship between conventional and lower baseline 11C-PiB PET thresholds for raised amyloid load and the subsequent clinical and radiological progression of mild cognitive impairment (MCI) cases longitudinally. METHODS: We serially determined the cortical amyloid load with 11C-PiB PET of 44 MCI subjects over 2 years and compared findings with those for 12 healthy controls (HC) and 5 AD cases. RESULTS: Twenty-four subjects were classified as normal at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2 and 1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over 2 years. Twenty-seven “raised amyloid” MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. Note that 50% of these cases converted clinically to AD during the follow-up period. CONCLUSION: Use of a PiB SUVR threshold of >1.5 for raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive amyloid increase over 2 years. Lowering the threshold for abnormality to 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.",
keywords = "11C-Pittsburgh compound-B, Alzheimer's disease, Amyloid-β, mild cognitive impairment, positron emission tomography",
author = "Rola Ismail and Peter Parbo and Hansen, {Kim V.} and Schaldemose, {Jeppe L.} and Dalby, {Rikke B.} and Anna Tietze and Kjeldsen, {Pernille L.} and {la Cour}, {Sanne Hage} and Per Qvist and Hanne Gottrup and Eskildsen, {Simon F.} and Brooks, {David J.}",
year = "2019",
month = jul,
day = "1",
doi = "10.1111/jon.12629",
language = "English",
volume = "29",
pages = "499--505",
journal = "Journal of Neuroimaging",
issn = "1051-2284",
publisher = "Wiley-Blackwell Publishing, Inc.",
number = "4",

}

RIS

TY - JOUR

T1 - Abnormal Amyloid Load in Mild Cognitive Impairment

T2 - The Effect of Reducing the PiB-PET Threshold

AU - Ismail, Rola

AU - Parbo, Peter

AU - Hansen, Kim V.

AU - Schaldemose, Jeppe L.

AU - Dalby, Rikke B.

AU - Tietze, Anna

AU - Kjeldsen, Pernille L.

AU - la Cour, Sanne Hage

AU - Qvist, Per

AU - Gottrup, Hanne

AU - Eskildsen, Simon F.

AU - Brooks, David J.

PY - 2019/7/1

Y1 - 2019/7/1

N2 - BACKGROUND AND PURPOSE: In vivo detection of β-amyloid (Aβ) plaques in Alzheimer's disease (AD) is now possible with 11C-PiB positron emission tomography (PET). Conventionally, a cortical:cerebellar PiB uptake ratio threshold of 1.4-1.5 has been used to categorize at-risk subjects as “amyloid-positive” and “amyloid-negative.” It has been suggested that this threshold is too conservative and may miss early amyloid pathology. We investigated the relationship between conventional and lower baseline 11C-PiB PET thresholds for raised amyloid load and the subsequent clinical and radiological progression of mild cognitive impairment (MCI) cases longitudinally. METHODS: We serially determined the cortical amyloid load with 11C-PiB PET of 44 MCI subjects over 2 years and compared findings with those for 12 healthy controls (HC) and 5 AD cases. RESULTS: Twenty-four subjects were classified as normal at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2 and 1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over 2 years. Twenty-seven “raised amyloid” MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. Note that 50% of these cases converted clinically to AD during the follow-up period. CONCLUSION: Use of a PiB SUVR threshold of >1.5 for raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive amyloid increase over 2 years. Lowering the threshold for abnormality to 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.

AB - BACKGROUND AND PURPOSE: In vivo detection of β-amyloid (Aβ) plaques in Alzheimer's disease (AD) is now possible with 11C-PiB positron emission tomography (PET). Conventionally, a cortical:cerebellar PiB uptake ratio threshold of 1.4-1.5 has been used to categorize at-risk subjects as “amyloid-positive” and “amyloid-negative.” It has been suggested that this threshold is too conservative and may miss early amyloid pathology. We investigated the relationship between conventional and lower baseline 11C-PiB PET thresholds for raised amyloid load and the subsequent clinical and radiological progression of mild cognitive impairment (MCI) cases longitudinally. METHODS: We serially determined the cortical amyloid load with 11C-PiB PET of 44 MCI subjects over 2 years and compared findings with those for 12 healthy controls (HC) and 5 AD cases. RESULTS: Twenty-four subjects were classified as normal at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2 and 1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over 2 years. Twenty-seven “raised amyloid” MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. Note that 50% of these cases converted clinically to AD during the follow-up period. CONCLUSION: Use of a PiB SUVR threshold of >1.5 for raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive amyloid increase over 2 years. Lowering the threshold for abnormality to 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.

KW - 11C-Pittsburgh compound-B

KW - Alzheimer's disease

KW - Amyloid-β

KW - mild cognitive impairment

KW - positron emission tomography

UR - http://www.scopus.com/inward/record.url?scp=85065657150&partnerID=8YFLogxK

U2 - 10.1111/jon.12629

DO - 10.1111/jon.12629

M3 - Journal article

C2 - 31074062

AN - SCOPUS:85065657150

VL - 29

SP - 499

EP - 505

JO - Journal of Neuroimaging

JF - Journal of Neuroimaging

SN - 1051-2284

IS - 4

ER -