Computerized decision support is an effective approach to select memory clinic patients for amyloid-PET

PLoS One. 2024 May 20;19(5):e0303111. doi: 10.1371/journal.pone.0303111. eCollection 2024.

Abstract

Background: The use of amyloid-PET in dementia workup is upcoming. At the same time, amyloid-PET is costly and limitedly available. While the appropriate use criteria (AUC) aim for optimal use of amyloid-PET, their limited sensitivity hinders the translation to clinical practice. Therefore, there is a need for tools that guide selection of patients for whom amyloid-PET has the most clinical utility. We aimed to develop a computerized decision support approach to select patients for amyloid-PET.

Methods: We included 286 subjects (135 controls, 108 Alzheimer's disease dementia, 33 frontotemporal lobe dementia, and 10 vascular dementia) from the Amsterdam Dementia Cohort, with available neuropsychology, APOE, MRI and [18F]florbetaben amyloid-PET. In our computerized decision support approach, using supervised machine learning based on the DSI classifier, we first classified the subjects using only neuropsychology, APOE, and quantified MRI. Then, for subjects with uncertain classification (probability of correct class (PCC) < 0.75) we enriched classification by adding (hypothetical) amyloid positive (AD-like) and negative (normal) PET visual read results and assessed whether the diagnosis became more certain in at least one scenario (PPC≥0.75). If this was the case, the actual visual read result was used in the final classification. We compared the proportion of PET scans and patients diagnosed with sufficient certainty in the computerized approach with three scenarios: 1) without amyloid-PET, 2) amyloid-PET according to the AUC, and 3) amyloid-PET for all patients.

Results: The computerized approach advised PET in n = 60(21%) patients, leading to a diagnosis with sufficient certainty in n = 188(66%) patients. This approach was more efficient than the other three scenarios: 1) without amyloid-PET, diagnostic classification was obtained in n = 155(54%), 2) applying the AUC resulted in amyloid-PET in n = 113(40%) and diagnostic classification in n = 156(55%), and 3) performing amyloid-PET in all resulted in diagnostic classification in n = 154(54%).

Conclusion: Our computerized data-driven approach selected 21% of memory clinic patients for amyloid-PET, without compromising diagnostic performance. Our work contributes to a cost-effective implementation and could support clinicians in making a balanced decision in ordering additional amyloid PET during the dementia workup.

MeSH terms

  • Aged
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / metabolism
  • Amyloid / metabolism
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism
  • Dementia, Vascular / diagnostic imaging
  • Dementia, Vascular / metabolism
  • Female
  • Frontotemporal Dementia / diagnostic imaging
  • Frontotemporal Dementia / metabolism
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Middle Aged
  • Positron-Emission Tomography* / methods

Grants and funding

The Vrije Universiteit Medical Center Alzheimer Center is supported by the Stichting Alzheimer Nederland and Stichting Vrije Universiteit Medical Center Fonds. The clinical database structure was developed with funding from Stichting Dioraphte. For development of the PredictAD tool, VTT Technical Research Centre of Finland has received funding from European Union’s Seventh Framework Programme for research, technological development and demonstration under grant agreements 601055 (VPH-DARE@IT) ), 224328 (PredictAD), and 611005 (PredictND). The collaboration project DAILY (project number LSHM19123-HSGF) is co-funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships. The ABIDE clinical utility study is funded by the PPP Allowance made available by Health-Holland, Top Sector Life Sciences & Health, to stimulate public-private partnerships and co-funded by Life Molecular Imaging GmbH (grant no. LSHM18075). HR is the recipient of the Memorable Dementia Fellowship 2021 (ZonMw project number 10510022110004) and Alzheimer Nederland InterACT grant (project number WE.08-2022-06). LC is supported by the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 115952. This Joint Undertaking receives the support from the European Union’s Horizon 2020 research and innovation program and EFPIA. FB is supported by the NIHR biomedical research centre at UCLH. The chair of WF is supported by the Pasman Stichting. WF is recipient of ABOARD, which is a public–private partnership receiving funding from ZonMW (number 73305095007) and Health-Holland, Top Sector Life Sciences and Health (public–private partnership allowance; number LSHM2010). HR and WF are recipients of Prominent. The Prominent project is supported by the Innovative Health Initiative Joint Undertaking (JU) under grant agreement no. 101112145. The JU receives support from the European Union’s Horizon Europe research and innovation programme and COCIR, EFPIA, EuropaBio MedTech Europe, Vaccines Europe, BioArctic AB and Combinostics Oy. Views and opinions expressed are those of the authors and do not necessarily reflect those of the aforementioned parties. Neither of the aforementioned parties can be held responsible for them.