Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults

Hammers, Dustin B.; Atkinson, Taylor J; Dalley, Bonnie C A; Suhrie, Kayla R; Horn, Kevin P.; Rasmussen, Kelli M; Beardmore, Britney; Burrell, Lance D.; Duff, Kevin; Hoffman, John M.

doi:10.1177/1533317517698795

Cited by 14 publications

(7 citation statements)

References 67 publications

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“…"The Centiloid Project" was recently published with the purpose to standardize the semi-quantification of Aβ-PET (7). To our knowledge, no studies have compared standardized uptake value ratios (SUVR) from commercially available software for semi-quantification of 18 F-Flutemetamol PET, although methods of semi-quantification have been explored quite extensively (9,(13)(14)(15)(16). Hence, it is of interest to explore differences in SUVR obtained from different software and compare SUVR and Centiloid (CL) with validated visual classification to facilitate appropriate use of semiquantification and thresholds in both research and clinical practice.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of semi-quantitative measures of 18F-flutemetamol PET for the clinical diagnosis of Alzheimer’s disease

Müller¹,

Stokke²,

Stokmo³

et al. 2022

Quant Imaging Med Surg

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Background: 18 F-Flutemetamol positron emission tomography (PET) is used to assess cortical amyloid-β burden in patients with cognitive impairment to support a clinical diagnosis. Visual classification is the most widely used method in clinical practice although semi-quantification is beneficial to obtain an objective and continuous measure of the Aβ burden. The aims were: first to evaluate the correspondence between standardized uptake value ratios (SUVRs) from three different software, Centiloids and visual classification, second to estimate thresholds for supporting visual classification and last to assess differences in semiquantitative measures between clinical diagnoses.Methods: This observational study included 195 patients with cognitive impairment who underwent 18 F-Flutemetamol PET. PET images were semi-quantified with SyngoVia, CortexID suite, and PMOD.Receiver operating characteristics curves were used to compare visual classification with composite SUVR normalized to pons (SUVRpons) and cerebellar cortex (SUVRcer), and Centiloids. We explored correlations and differences between semi-quantitative measures as well as differences in SUVR between two clinical diagnosis groups: Alzheimer's disease-group and non-Alzheimer's disease-group.Results: PET images from 191 patients were semi-quantified with SyngoVia and CortexID and 86 PETmagnetic resonance imaging pairs with PMOD. All receiver operating characteristics curves showed a high area under the curve (>0.98). Thresholds for a visually positive PET was for SUVRcer: 1.87 (SyngoVia) and 1.64 (CortexID) and for SUVRpons: 0.54 (SyngoVia) and 0.55 (CortexID). The threshold on the Centiloid scale was 39.6 Centiloids. All semi-quantitative measures showed a very high correlation between different software and normalization methods. Composite SUVRcer was significantly different between SyngoVia and PMOD, SyngoVia and CortexID but not between PMOD and CortexID. Composite SUVRpons were significantly different between all three software. There were significant differences in the mean rank of SUVRpons, SUVRcer, and Centiloid between Alzheimer's disease-group and non-Alzheimer's disease-group.

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Section: Introductionmentioning

confidence: 99%

Evaluation of semi-quantitative measures of 18F-flutemetamol PET for the clinical diagnosis of Alzheimer’s disease

Müller¹,

Stokke²,

Stokmo³

et al. 2022

Quant Imaging Med Surg

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“…In healthy controls, the use of SUVR measures and visual rating to predict decreased memory performances led to conflicting data. Cross-sectional studies failed to identify solid associations between 18 F-Flutemetamol or Florbetapir data (both visual cut-off and quantitative) and cognitive decrement 54,55 . Longitudinally, the INSIGHT-preAD study demonstrated that 18 F-Florbetapir SUVR values were not related to significant changes in MMSE scores over a 30-month period 56 .…”

Section: Discussionmentioning

confidence: 97%

PET amyloid in normal aging: direct comparison of visual and automatic processing methods

Haller

Montandon

Lilja

et al. 2020

Sci Rep

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Assessment of amyloid deposits is a critical step for the identification of Alzheimer disease (AD) signature in asymptomatic elders. Whether the different amyloid processing methods impacts on the quality of clinico-radiological correlations is still unclear. We directly compared in 155 elderly controls with extensive neuropsychological testing at baseline and 4.5 years follow-up three approaches: (i) operator-dependent standard visual reading, (ii) operator-independent automatic SUVR with four different reference regions, and (iii) novel operator and region of reference-independent automatic Aβ-index. The coefficient of variance was used to examine inter-individual variability for each processing method. Using visually-established amyloid positivity as the gold standard, the area under the receiver operating characteristic curve (ROC) was computed. Linear regression models were used to assess the association between changes in continuous cognitive score and amyloid uptake values. In SUVR analyses, the coefficient of variance varied from 1.718 to 1.762 according to the area of reference and was of − 3.045 for the Aβ-index method. Compared to the visual rating, Aβ-index method showed the largest area under the ROC curve [0.9568 (95% CI 0.9252, 0.98833)]. The best cut-off score was of − 0.3359 with sensitivity and specificity values of 0.97 and 0.83, respectively. Only the Aß-index was related to more severe decrement of cognitive performances [regression coefficient: 9.103 (95% CI 1.148, 17.058)]. The Aβ-index is considered as preferred option in asymptomatic elders, since it is operator-independent, avoids the selection of reference area, is closer to established visual scoring and correlates with the evolution of cognitive performances.

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“…Although amyloid-cognition correlations are debated, some studies reveal a declining cognitive functioning linked to amyloid deposition, even in CU individuals [ 40 , 46 ]. A weak, significant, negative partial correlation was found between the delayed RCFT and PC1 loadings (Fig.…”

Section: Discussionmentioning

confidence: 99%

Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78–94

et al. 2022

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Amyloid-beta (Aβ) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to 18F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aβ. Good correspondence existed between binary (+/−) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8–17% of individuals being unstageable, i.e., not following the sequential progression of Aβ deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aβ, thus, it remains an open topic what constitutes abnormal brain Aβ in the oldest-old and what is the best method to determine that.

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Amyloid Positivity Using [18F]Flutemetamol-PET and Cognitive Deficits in Nondemented Community-Dwelling Older Adults

Cited by 14 publications

References 67 publications

Evaluation of semi-quantitative measures of 18F-flutemetamol PET for the clinical diagnosis of Alzheimer’s disease

Evaluation of semi-quantitative measures of 18F-flutemetamol PET for the clinical diagnosis of Alzheimer’s disease

PET amyloid in normal aging: direct comparison of visual and automatic processing methods

Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78–94

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