Plasma biomarkers increase diagnostic confidence in patients with Alzheimer's disease or frontotemporal lobar degeneration.
Alzheimer’s disease
Diagnosis
Diagnostic confidence
Frontotemporal lobar degeneration
Plasma biomarkers
Journal
Alzheimer's research & therapy
ISSN: 1758-9193
Titre abrégé: Alzheimers Res Ther
Pays: England
ID NLM: 101511643
Informations de publication
Date de publication:
11 May 2024
11 May 2024
Historique:
received:
29
11
2023
accepted:
01
05
2024
medline:
12
5
2024
pubmed:
12
5
2024
entrez:
11
5
2024
Statut:
epublish
Résumé
The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer's disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center. Anonymized clinical reports of patients diagnosed with AD or Frontotemporal Lobar Degeneration with available plasma biomarkers (Aβ Clinicians assessed 122 reports, and their concordance ranged from 81 to 91% at the three time points. At T1, the presentation of plasma biomarkers resulted in a change of diagnosis in 2% (2/122, p = 1.00) of cases, and in increased diagnostic confidence in 76% (91/120, p < 0.001) of cases with confirmed diagnosis. The change in diagnosis and the increase in diagnostic confidence after plasma biomarkers were consistent with the final diagnosis in 100% (2/2) and 81% (74/91) of cases, respectively. At T2, the presentation of traditional biomarkers resulted in a further change of diagnosis in 13% (12/94, p = 0.149) of cases, and in increased diagnostic confidence in 88% (72/82, p < 0.001) of cases with confirmed diagnosis. In an academic tertiary care center, plasma biomarkers supported clinicians by increasing their diagnostic confidence in most cases, despite a negligible impact on diagnosis. Future prospective studies are needed to assess the full potential of plasma biomarkers on clinical grounds.
Sections du résumé
BACKGROUND
BACKGROUND
The recent development of techniques to assess plasma biomarkers has changed the way the research community envisions the future of diagnosis and management of Alzheimer's disease (AD) and other neurodegenerative disorders. This work aims to provide real world evidence on the clinical impact of plasma biomarkers in an academic tertiary care center.
METHODS
METHODS
Anonymized clinical reports of patients diagnosed with AD or Frontotemporal Lobar Degeneration with available plasma biomarkers (Aβ
RESULTS
RESULTS
Clinicians assessed 122 reports, and their concordance ranged from 81 to 91% at the three time points. At T1, the presentation of plasma biomarkers resulted in a change of diagnosis in 2% (2/122, p = 1.00) of cases, and in increased diagnostic confidence in 76% (91/120, p < 0.001) of cases with confirmed diagnosis. The change in diagnosis and the increase in diagnostic confidence after plasma biomarkers were consistent with the final diagnosis in 100% (2/2) and 81% (74/91) of cases, respectively. At T2, the presentation of traditional biomarkers resulted in a further change of diagnosis in 13% (12/94, p = 0.149) of cases, and in increased diagnostic confidence in 88% (72/82, p < 0.001) of cases with confirmed diagnosis.
CONCLUSIONS
CONCLUSIONS
In an academic tertiary care center, plasma biomarkers supported clinicians by increasing their diagnostic confidence in most cases, despite a negligible impact on diagnosis. Future prospective studies are needed to assess the full potential of plasma biomarkers on clinical grounds.
Identifiants
pubmed: 38734612
doi: 10.1186/s13195-024-01474-z
pii: 10.1186/s13195-024-01474-z
doi:
Substances chimiques
Biomarkers
0
Amyloid beta-Peptides
0
tau Proteins
0
Peptide Fragments
0
amyloid beta-protein (1-42)
0
Neurofilament Proteins
0
neurofilament protein L
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107Subventions
Organisme : Ministero dell'Università e della Ricerca
ID : 202223XMAF
Informations de copyright
© 2024. The Author(s).
Références
Sosa-Ortiz AL, Acosta-Castillo I, Prince MJ. Epidemiology of dementias and Alzheimer’s disease. Arch Med Res. 2012;43:600–8.
doi: 10.1016/j.arcmed.2012.11.003
pubmed: 23159715
Frisoni GB, Altomare D, Thal DR, et al. The probabilistic model of Alzheimer disease: the amyloid hypothesis revised. Nat Rev Neurosci. 2022;23:53–66.
doi: 10.1038/s41583-021-00533-w
pubmed: 34815562
Kumar A, Fontana IC, Nordberg A. Reactive astrogliosis: A friend or foe in the pathogenesis of Alzheimer’s disease. J Neurochem. 2023;164:309–24.
doi: 10.1111/jnc.15565
pubmed: 34931315
Rabinovici GD, Miller BL. Frontotemporal lobar degeneration: epidemiology, pathophysiology, diagnosis and management. CNS Drugs. 2010;24:375–98.
doi: 10.2165/11533100-000000000-00000
pubmed: 20369906
pmcid: 2916644
Caprioglio C, Garibotto V, Jessen F, et al. The Clinical Use of Alzheimer’s Disease Biomarkers in Patients with Mild Cognitive Impairment: A European Alzheimer’s Disease Consortium Survey. J Alzheimers Dis. 2022;89:535–51.
doi: 10.3233/JAD-220333
pubmed: 35912743
pmcid: 9535580
Aducanumab (marketed as Aduhelm) Information | FDA. https://www.fda.gov/drugs/postmarket-drug-safety-information-patients-and-providers/aducanumab-marketed-aduhelm-information . Accessed 3 Jan 2023.
FDA Grants Accelerated Approval for Alzheimer’s Disease Treatment | FDA. https://www.fda.gov/news-events/press-announcements/fda-grants-accelerated-approval-alzheimers-disease-treatment . Accessed 10 Jan 2023.
Schindler SE, Bollinger JG, Ovod V, et al. High-precision plasma β-amyloid 42/40 predicts current and future brain amyloidosis. Neurology. 2019;93:E1647–59.
doi: 10.1212/WNL.0000000000008081
pubmed: 31371569
pmcid: 6946467
Karikari TK, Pascoal TA, Ashton NJ, et al. Blood phosphorylated tau 181 as a biomarker for Alzheimer’s disease: a diagnostic performance and prediction modelling study using data from four prospective cohorts. Lancet Neurol. 2020;19:422–33.
doi: 10.1016/S1474-4422(20)30071-5
pubmed: 32333900
Ashton NJ, Pascoal TA, Karikari TK, et al. Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol. 2021;141:709–24.
doi: 10.1007/s00401-021-02275-6
pubmed: 33585983
pmcid: 8043944
Milà-Alomà M, Ashton NJ, Shekari M, et al. Plasma p-tau231 and p-tau217 as state markers of amyloid-β pathology in preclinical Alzheimer’s disease. Nat Med. 2022;28:1797–801.
pubmed: 35953717
pmcid: 9499867
Ashton NJ, Janelidze S, Al Khleifat A, et al. A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. 2021;12. https://doi.org/10.1038/S41467-021-23620-Z .
Pereira JB, Janelidze S, Smith R, et al. Plasma GFAP is an early marker of amyloid-β but not tau pathology in Alzheimer’s disease. Brain. 2021;144:3505–16.
doi: 10.1093/brain/awab223
pubmed: 34259835
pmcid: 8677538
Altomare D, Stampacchia S, Ribaldi F, Tomczyk S, Chevalier C, Poulain G, Asadi S, Bancila B, Marizzoni M, Martins M, Lathuiliere A, Scheffler M, Ashton NJ, Zetterberg H, Blennow K, Kern I, Frias M, Garibotto V, Frisoni GB. Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic. J Neurol Neurosurg Psychiatry. 2023;94(6):420–7. https://doi.org/10.1136/jnnp-2022-330619 , https://pubmed.ncbi.nlm.nih.gov/37012066/ .
Teunissen CE, Verberk IMW, Thijssen EH, et al. Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol. 2022;21:66–77.
doi: 10.1016/S1474-4422(21)00361-6
pubmed: 34838239
McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:263–9.
doi: 10.1016/j.jalz.2011.03.005
pubmed: 21514250
Albert MS, DeKosky ST, Dickson D, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7:270–9.
doi: 10.1016/j.jalz.2011.03.008
pubmed: 21514249
Rascovsky K, Hodges JR, Knopman D, et al. Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain. 2011;134:2456–77.
doi: 10.1093/brain/awr179
pubmed: 21810890
pmcid: 3170532
Gorno-Tempini ML, Hillis AE, Weintraub S, et al. Classification of primary progressive aphasia and its variants. Neurology. 2011;76:1006–14.
doi: 10.1212/WNL.0b013e31821103e6
pubmed: 21325651
pmcid: 3059138
Armstrong MJ, Litvan I, Lang AE, et al. Criteria for the diagnosis of corticobasal degeneration. Neurology. 2013;80:496–503.
doi: 10.1212/WNL.0b013e31827f0fd1
pubmed: 23359374
pmcid: 3590050
Höglinger GU, Respondek G, Stamelou M, et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32:853–64.
doi: 10.1002/mds.26987
pubmed: 28467028
pmcid: 5516529
Lomen-Hoerth C, Anderson T, Miller B. The overlap of amyotrophic lateral sclerosis and frontotemporal dementia. Neurology. 2002;59:1077–9.
doi: 10.1212/WNL.59.7.1077
pubmed: 12370467
Burrell JR, Kiernan MC, Vucic S, Hodges JR. Motor neuron dysfunction in frontotemporal dementia. Brain. 2011;134:2582–94.
doi: 10.1093/brain/awr195
pubmed: 21840887
Benussi A, Cantoni V, Rivolta J, et al. Classification accuracy of blood-based and neurophysiological markers in the differential diagnosis of Alzheimer’s disease and frontotemporal lobar degeneration. Alzheimers Res Ther. 2022;14. https://doi.org/10.1186/S13195-022-01094-5 .
Altomare D, Barkhof F, Caprioglio C, et al. Clinical effect of early vs late amyloid positron emission tomography in memory clinic patients: The AMYPAD-DPMS randomized clinical trial. JAMA Neurol. 2023;80. https://doi.org/10.1001/JAMANEUROL.2023.0997 .
Ossenkoppele R, Prins ND, Pijnenburg YAL, et al. Impact of molecular imaging on the diagnostic process in a memory clinic. Alzheimers Dement. 2013;9:414–21.
doi: 10.1016/j.jalz.2012.07.003
pubmed: 23164552
Zwan MD, Bouwman FH, Konijnenberg E, et al. Diagnostic impact of [18F]flutemetamol PET in early-onset dementia. Alzheimers Res Ther. 2017;9:2.
doi: 10.1186/s13195-016-0228-4
pubmed: 28093088
pmcid: 5240413
Pontecorvo MJ, Siderowf A, Dubois B, et al. Effectiveness of florbetapir PET imaging in changing patient management. Dement Geriatr Cogn Disord. 2017;44:129–43.
doi: 10.1159/000478007
pubmed: 28787712
De Wilde A, Van Der Flier WM, Pelkmans W, et al. Association of amyloid positron emission tomography with changes in diagnosis and patient treatment in an unselected memory clinic cohort: The ABIDE project. JAMA Neurol. 2018;75:1062–70.
doi: 10.1001/jamaneurol.2018.1346
pubmed: 29889941
pmcid: 6143118
Hattori N, Sherwin P, Farrar G. Initial physician experience with [18 F] flutemetamol amyloid PET imaging following availability for routine clinical use in Japan. J Alzheimers Dis Rep. 2020;4:165–74.
doi: 10.3233/ADR-190150
pubmed: 32715277
pmcid: 7369136
Benussi A, Ashton NJ, Karikari TK, et al. Serum Glial Fibrillary Acidic Protein (GFAP) is a marker of disease severity in frontotemporal lobar degeneration. J Alzheimers Dis. 2020;77:1129–41.
doi: 10.3233/JAD-200608
pubmed: 32804092
Benussi A, Karikari TK, Ashton N, et al. Diagnostic and prognostic value of serum NfL and p-Tau181 in frontotemporal lobar degeneration. J Neurol Neurosurg Psychiatry. 2020;91:960–7.
doi: 10.1136/jnnp-2020-323487
pubmed: 32611664
Simren J, Andreasson U, Gobom J, et al. Establishment of reference values for plasma neurofilament light based on healthy individuals aged 5–90 years. Brain Commun. 2022;4. https://doi.org/10.1093/BRAINCOMMS/FCAC174 .
Altomare D, Molinuevo JL, Ritchie C, et al. Brain health services: organization, structure, and challenges for implementation. A user manual for Brain Health Services-part 1 of 6. Alzheimers Res Ther. 2021;13. https://doi.org/10.1186/S13195-021-00827-2 .
Rabe C, Bittner T, Jethwa A, et al. Clinical performance and robustness evaluation of plasma amyloid-β42/40 prescreening. Alzheimers Dement. 2023;19. https://doi.org/10.1002/ALZ.12801 .
Benedet AL, Brum WS, Hansson O, et al. The accuracy and robustness of plasma biomarker models for amyloid PET positivity. Alzheimers Res Ther. 2022;14. https://doi.org/10.1186/S13195-021-00942-0 .
Ashton NJ, Puig-Pijoan A, Milà-Alomà M, et al. Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays. Alzheimers Dement. 2023;19:1913–24.
doi: 10.1002/alz.12841
pubmed: 36370462
Ashton NJ, Janelidze S, Mattsson-Carlgren N, et al. Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring. Nat Med. 2022;28:2555–62.
doi: 10.1038/s41591-022-02074-w
pubmed: 36456833
pmcid: 9800279