Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design

Wilde, Arno de; Maurik, Ingrid S. van; Kunneman, Marleen; Bouwman, Femke H.; Zwan, Marissa D.; Willemse, Eline A.J.; Biessels, Geert Jan; Minkman, Mirella; Pel, Ruth; Schoonenboom, Niki S.M.; Smets, Ellen M. A.; Wattjes, Mike P.; Barkhof, Frederik; Stephens, Andrew; Lier, E.; Batrla-Utermann, Richard; Scheltens, Philip; Teunissen, Charlotte E.; Berckel, Bart N.M. van; Flier, Wiesje M. van der

doi:10.1016/j.dadm.2017.01.003

Cited by 65 publications

(83 citation statements)

References 48 publications

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“…This study analyzes data acquired as part of the AD biomarkers in daily practice (ABIDE) project that focuses on the optimal use of diagnostics test, including CSF, in daily clinical practice [23]. For the present study, we included patients that were screened for suspected AD in eight nonacademic local memory clinics.…”

Section: Patientsmentioning

confidence: 99%

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

Willemse

Maurik

Tijms

et al. 2018

Alz & Dem Diag Ass & Dis Mo

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Introduction We compared the automated Elecsys and manual Innotest immunoassays for cerebrospinal fluid (CSF) Alzheimer's disease biomarkers in a multicenter diagnostic setting. Methods We collected CSF samples from 137 participants in eight local memory clinics. Amyloid β(1–42) (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) were centrally analyzed with Innotest and Elecsys assays. Concordances between methods were assessed. Results Biomarker results strongly correlated between assays with Spearman's ρ 0.94 for Aβ42, 0.98 for t-tau, and 0.98 for p-tau. Using Gaussian mixture modeling, cohort-specific cut-points were estimated at 1092 pg/mL for Aβ42, 235 pg/mL for t-tau, and 24 pg/mL for p-tau. We found an excellent concordance of biomarker abnormality between assays of 97% for Aβ42 and 96% for both t-tau and p-tau. Discussion The high concordances between Elecsys and Innotest in this nonacademic, multicenter cohort support the use of Elecsys for CSF Alzheimer's disease diagnostics and allow conversion of results between methods.

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Section: Patientsmentioning

confidence: 99%

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

Willemse

Maurik

Tijms

et al. 2018

Alz & Dem Diag Ass & Dis Mo

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“…Patients underwent an amyloid-β PET for research purposes in the vast majority (38)(39)(40)(41)(42)(43) or otherwise in case of a diagnostic dilemma. Amyloid-β PET scans were performed using the following PET scanners:…”

Section: Petmentioning

confidence: 99%

“…ECAT EXACT HR+ scanner (Siemens Healthcare, Germany) and Gemini TF PET/CT, Ingenuity TF PET-CT and Ingenuity PET/MRI (Philips Medical Systems, the Netherlands). We included PET scans using four different radiotracers: [ 18 F]Florbetaben (38,43)…”

Section: Petmentioning

confidence: 99%

PET and CSF amyloid-β status are differently predicted by patient features: Information from discordant cases

Reimand

Wilde

Teunissen

et al. 2019

Preprint

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Background:Amyloid-β PET and CSF Aβ42 yield discordant results in 10-20% of patients, possibly providing unique information. Although the predictive power of demographic, clinical, genetic and imaging features for amyloid-positivity has previously been investigated, it is unknown whether these features differentially predict amyloid-β status based on PET or CSF, or whether this differs by disease stage. Methods:We included 768 patients (subjective cognitive decline (SCD, n=194), mild cognitive impairment (MCI, n=127), dementia (AD and non-AD, n=447) with amyloid-β PET and CSF Aβ42 measurement within oneyear. 97(13%) patients had discordant PET/CSF amyloid-β status. We performed parallel random forest models predicting separately PET and CSF status using 17 patient features (demographics, APOE4 positivity, CSF (p)tau, cognitive performance, and MRI visual ratings) in the total patient group and stratified by syndrome diagnosis. Thereafter, we selected features with the highest variable importance measure (VIM) as input for logistic regression models, where amyloid status on either PET or CSF was predicted by (i) the selected patient feature, and (ii) the patient feature adjusted for the status of the other amyloid modality. Results:APOE4, CSF tau and p-tau had highest VIM for PET and CSF in all groups. In the amyloid-adjusted logistic regression models, p-tau was a significant predictor for PET-amyloid in SCD (OR=1.02[1.01-1.04], pFDR=0.03), MCI (OR=1.05[1.02-1.07], pFDR<0.01) and dementia (OR=1.04[1.03-1.05], pFDR<0.001), but not for CSF-amyloid. APOE4 (OR=3.07[1.33-7.07], punc<0.01) was associated with CSF-amyloid in SCD, while it was only predictive for PET-amyloid in MCI (OR=9.44[2.93,30.39], pFDR<0.01). Worse MMSE scores (OR=1.21[1.03-1.41], punc=0.02) were associated to CSF-amyloid status in SCD, whereas worse memory (OR=1.17[1.05-1.31], pFDR=0.02) only predicted PET positivity in dementia. Conclusion :Amyloid status based on either PET or CSF was predicted by different patient features and this varied by disease stage, suggesting that PET-CSF discordance yields unique information. The stronger associations of both APOE4 carriership and worse memory z-scores with CSF-amyloid in SCD suggests that CSF-amyloid is more sensitive early in the disease course. The higher predictive value of CSF p-tau for a positive PET scan suggests that PET is more specific to AD pathology. These findings can influence the choice between amyloid biomarkers in future studies or trials.

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“…Whether, when and if so how MCI patients will develop dementia is still difficult to predict . Second, novel diagnostic measures are developed to enable earlier and a more accurate diagnosis of AD . Examples are tests detecting biomarkers through imaging techniques or in cerebrospinal fluid (CSF) .…”

Section: Introductionmentioning

confidence: 99%

“…However, these tests do not always provide the desired certainty . The interpretation of diagnostic test results is often complicated, for instance when they are borderline abnormal or conflicting . In addition, for individuals without dementia, results of AD‐biomarker diagnostic tests only yield a risk indication of developing dementia within the next years .…”

Section: Introductionmentioning

confidence: 99%

Communicating uncertainties when disclosing diagnostic test results for (Alzheimer's) dementia in the memory clinic: The ABIDE project

Visser

Pelt

Kunneman

et al. 2019

Health Expectations

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Background: The development of novel diagnostics enables increasingly earlier diagnosis of Alzheimer's disease (AD). Timely diagnosis may benefit patients by reducing their uncertainty regarding the cause of symptoms, yet does not always provide patients with the desired certainty. Objective: To examine, using both quantitative and qualitative methods, uncertainty communicated by memory clinic clinicians in post-diagnostic testing consultations with patients and their caregivers. Methods: First, we identified all uncertainty expressions of 22 clinicians in audiotaped post-diagnostic testing consultations with 78 patients. Second, we statistically | 53 VISSER Et al.

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Alzheimer's biomarkers in daily practice (ABIDE) project: Rationale and design

Cited by 65 publications

References 48 publications

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

Diagnostic performance of Elecsys immunoassays for cerebrospinal fluid Alzheimer's disease biomarkers in a nonacademic, multicenter memory clinic cohort: The ABIDE project

PET and CSF amyloid-β status are differently predicted by patient features: Information from discordant cases

Communicating uncertainties when disclosing diagnostic test results for (Alzheimer's) dementia in the memory clinic: The ABIDE project

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