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

Lookup NU author(s): Professor David BrooksORCiD



This is the authors' accepted manuscript of an article that has been published in its final definitive form by Wiley, 2019.

For re-use rights please refer to the publisher's terms and conditions.


Background and purpose: In vivo detection of b-amyloid (Ab) 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 categorise 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 two years and compared findings with those for 12 healthy controls (HC) and 5 AD cases.Results: Twenty-four subjects were classified as normal Abload at baseline with mean cortical PiB standard uptake value ratios (SUVR) between 1.2-1.5. Their cognitive status remained stable over time. Three of these cases increased their amyloid load above a threshold of 1.5 over two years. Twenty-seven ‘raised Ab’ MCI cases with baseline cortical SUVRs above 1.5, showed deteriorating cognition. 50% of these cases converted clinically to AD during the follow-up period. Conclusion: Use of a PiB SUVR threshold of >1.5 to categorise subjects as having raised amyloid missed 14.3% of MCI cases who likely had Thal stage 1 or 2 pathology and showed a progressive Abload increase over two years. Lowering the threshold for abnormally raised Abto 1.3 abolished all false negatives but resulted in 75% of HCs being falsely diagnosed as raised amyloid subjects.

Publication metadata

Author(s): Ismail R, Parbo P, Hansen KV, Schaldemose JL, Dalby JB, Tietze A, Kjeldsen PL, LaCour SH, Qvist P, Gottrup H, Eskildsen SF, Brooks DJ

Publication type: Article

Publication status: Published

Journal: Journal of Neuroimaging

Year: 2019

Volume: 29

Issue: 4

Pages: 499-505

Print publication date: 01/07/2019

Online publication date: 10/05/2019

Acceptance date: 30/04/2019

Date deposited: 30/04/2019

ISSN (print): 1051-2284

ISSN (electronic): 1552-6569

Publisher: Wiley


DOI: 10.1111/jon.12629


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