Biomarkers for the diagnosis of Alzheimer's disease in clinical practice: an Italian intersocietal roadmap

Frisoni, Giovanni B.; Perani, Daniela; Bastianello, Stefano; Bernardi, Gaetano; Porteri, Corinna; Boccardi, Marina; Cappa, Stefano F.; Trabucchi, Marco; Padovani, Alessandro

doi:10.1016/j.neurobiolaging.2016.02.033

Cited by 17 publications

(17 citation statements)

References 73 publications

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“…Their accuracy depends on the type (e.g., amyloid PET imaging, FDG-PET or MRI) as well as on the measurement method [36]. Semi-quantitative or quantitative assessment and standard operating procedures are strongly suggested by scientific societies as key to a welladvised use of biomarkers in research, clinical settings and trials [37]. In addition, the combined use of different biomarkers and the standardized procedures are expected to facilitate the diagnostic process at the single-subject level [38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

Perani

Cerami

Caminiti

et al. 2015

Eur J Nucl Med Mol Imaging

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In this clinical setting, FDG PET SPM t-maps and the p-tau/Aβ42 ratio improved clinical diagnostic accuracy, supporting the importance of these biomarkers in the emerging diagnostic criteria for Alzheimer's disease dementia. FDG PET using SPM t-maps had the highest predictive value by identifying hypometabolic patterns in different neurodegenerative dementias and normal brain metabolism in MCI, confirming its additional crucial exclusionary role.

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Section: Introductionmentioning

confidence: 99%

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

Perani

Cerami

Caminiti

et al. 2015

Eur J Nucl Med Mol Imaging

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“…On the basis of our study design, in which amyloid PET results were used to revise initial diagnoses and treatment plans, our findings provide an estimate of the incremental value of this type of investigation in the clinical setting. Thus, this study fulfils the requirements of a phase 4 study as defined by the five-phase biomarker validation framework recently introduced to the field [ 34 , 35 ]. This type of study is vital to assess the utility of amyloid PET and to accelerate the development of evidence-based guidelines for its clinical use [ 36 ].…”

Section: Discussionmentioning

confidence: 92%

Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis

Leuzy

Savitcheva

Chiotis

et al. 2019

Eur J Nucl Med Mol Imaging

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Purpose To investigate the impact of amyloid PET with [ 18 F]flutemetamol on diagnosis and treatment management in a cohort of patients attending a tertiary memory clinic in whom, despite extensive cognitive assessment including neuropsychological testing, structural imaging, CSF biomarker analysis and in some cases [ 18 F]FDG PET, the diagnosis remained unclear. Methods The study population consisted of 207 patients with a clinical diagnosis prior to [ 18 F]flutemetamol PET including mild cognitive impairment (MCI; n = 131), Alzheimer’s disease (AD; n = 41), non-AD ( n = 10), dementia not otherwise specified (dementia NOS; n = 20) and subjective cognitive decline (SCD; n = 5). Results Amyloid positivity was found in 53% of MCI, 68% of AD, 20% of non-AD, 20% of dementia NOS, and 60% of SCD patients. [ 18 F]Flutemetamol PET led, overall, to a change in diagnosis in 92 of the 207 patients (44%). A high percentage of patients with a change in diagnosis was observed in the MCI group ( n = 67, 51%) and in the dementia NOS group ( n = 11; 55%), followed by the non-AD and AD (30% and 20%, respectively). A significant increase in cholinesterase inhibitor treatment was observed after [ 18 F]flutemetamol PET (+218%, 34 patients before and 108 patients after). Conclusion The present study lends support to the clinical value of amyloid PET in patients with an uncertain diagnosis in the tertiary memory clinic setting.

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“…The evidence for the clinical validity of different biomarkers for dementia in AD, including FDG-PET, has been recently revised in a validation framework derived from oncology [11, 14-16]. One secondary aim of phase 2 of the validation process, which concerns the use of the assay in the clinical disease phase, is the assessment of factors associated with biomarker status or level in control subjects and in patients.…”

Section: Discussionmentioning

confidence: 99%

Education-Adjusted Normality Thresholds for FDG-PET in the Diagnosis of Alzheimer Disease

et al. 2018

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Background: A corollary of the reserve hypothesis is that what is regarded as pathological cortical metabolism in patients might vary according to education. Objective: The aim of this study is to assess the incremental diagnostic value of education-adjusted over unadjusted thresholds on the diagnostic accuracy of FDG-PET as a biomarker for Alzheimer disease (AD). Methods: We compared cortical metabolism in 90 healthy controls and 181 AD patients from the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The AUC of the ROC curve did not differ significantly between the whole group and the higher-education patients or the lower-education subjects. Results: The threshold of wMetaROI values providing 80% sensitivity was lower in higher-education patients and higher in the lower-education patients, compared to the standard threshold derived over the whole AD collective, without, however, significant changes in sensitivity and specificity. Conclusion: These data show that education, as a proxy of reserve, is not a major confounder in the diagnostic accuracy of FDG-PET in AD and the adoption of education-adjusted thresholds is not required in daily practice.

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Biomarkers for the diagnosis of Alzheimer's disease in clinical practice: an Italian intersocietal roadmap

Cited by 17 publications

References 73 publications

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

Cross-validation of biomarkers for the early differential diagnosis and prognosis of dementia in a clinical setting

Clinical impact of [18F]flutemetamol PET among memory clinic patients with an unclear diagnosis

Education-Adjusted Normality Thresholds for FDG-PET in the Diagnosis of Alzheimer Disease

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