Impact of demographics and comorbid conditions on plasma biomarkers concentrations and their diagnostic accuracy in a memory clinic cohort.
Blood biomarkers
Comorbidities
Dementia
Diagnostic performance
Neurodegenerative diseases
Journal
Journal of neurology
ISSN: 1432-1459
Titre abrégé: J Neurol
Pays: Germany
ID NLM: 0423161
Informations de publication
Date de publication:
27 Dec 2023
27 Dec 2023
Historique:
received:
22
10
2023
accepted:
07
12
2023
revised:
05
12
2023
medline:
28
12
2023
pubmed:
28
12
2023
entrez:
27
12
2023
Statut:
aheadofprint
Résumé
Plasma biomarkers have emerged as promising tools for identifying amyloid beta (Aβ) pathology. Before implementation in routine clinical practice, confounding factors modifying their concentration beyond neurodegenerative diseases should be identified. We studied the association of a comprehensive list of demographics, comorbidities, medication and laboratory parameters with plasma p-tau181, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) on a prospective memory clinic cohort and studied their impact on diagnostic accuracy for discriminating CSF/amyloid PET-defined Aβ status. Three hundred sixty patients (mean age 66.5 years, 55% females, 53% Aβ positive) were included. Sex, age and Aβ status-adjusted models showed that only estimated glomerular filtration rate (eGFR, standardized β -0.115 [-0.192 to -0.035], p = 0.005) was associated with p-tau181 levels, although with a much smaller effect than Aβ status (0.685 [0.607-0.763], p < 0.001). Age, sex, body mass index (BMI), Charlson comorbidity index (CCI) and eGFR significantly modified GFAP concentration. Age, blood volume (BV) and eGFR were associated with NfL levels. p-tau181 predicted Aβ status with 87% sensitivity and specificity with no relevant increase in diagnostic performance by adding any of the confounding factors. Using two cut-offs, plasma p-tau181 could have spared 62% of amyloid-PET/CSF testing. Excluding patients with chronic kidney disease did not change the proposed cut-offs nor the diagnostic performance. In conclusion, in a memory clinic cohort, age, sex, eGFR, BMI, BV and CCI slightly modified plasma p-tau181, GFAP and NfL concentrations but their impact on the diagnostic accuracy of plasma biomarkers for Aβ status discrimination was minimal.
Identifiants
pubmed: 38151575
doi: 10.1007/s00415-023-12153-8
pii: 10.1007/s00415-023-12153-8
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Alzheimer's Association
ID : AACSF-21-723056
Pays : United States
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.
Références
Gonzalez-Ortiz F, Kac PR, Brum WS et al (2023) Plasma phospho-tau in Alzheimer’s disease: towards diagnostic and therapeutic trial applications. Mol Neurodegener 18:1–12. https://doi.org/10.1186/s13024-023-00605-8
doi: 10.1186/s13024-023-00605-8
Hansson O, Edelmayer RM, Boxer AL et al (2022) The Alzheimer’s Association appropriate use recommendations for blood biomarkers in Alzheimer’s disease. Alzheimer’s Dement. https://doi.org/10.1002/alz.12756
doi: 10.1002/alz.12756
Ashton NJ, Janelidze S, Mattsson-Carlgren N et al (2022) Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring. Nat Med. https://doi.org/10.1038/s41591-022-02074-w
doi: 10.1038/s41591-022-02074-w
pubmed: 36456833
pmcid: 9800279
Teunissen CE, Verberk IMW, Thijssen EH et al (2022) Blood-based biomarkers for Alzheimer’s disease: towards clinical implementation. Lancet Neurol 21:66–77
doi: 10.1016/S1474-4422(21)00361-6
pubmed: 34838239
Karikari TK, Ashton NJ, Brinkmalm G et al (2022) Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility. Nat Rev Neurol 18:400–418. https://doi.org/10.1038/s41582-022-00665-2
doi: 10.1038/s41582-022-00665-2
pubmed: 35585226
van Dyck CH, Swanson CJ, Aisen P et al (2023) Lecanemab in early Alzheimer’s disease. N Engl J Med 388:9–21. https://doi.org/10.1056/NEJMoa2212948
doi: 10.1056/NEJMoa2212948
pubmed: 36449413
Sims JR, Zimmer JA, Evans CD et al (2023) Donanemab in early symptomatic Alzheimer disease. JAMA 330:512. https://doi.org/10.1001/jama.2023.13239
doi: 10.1001/jama.2023.13239
pubmed: 37459141
Sarto J, Ruiz-García R, Guillén N et al (2022) Diagnostic performance and clinical applicability of blood-based biomarkers in a prospective memory clinic cohort. Neurology. https://doi.org/10.1212/WNL.0000000000201597
doi: 10.1212/WNL.0000000000201597
pubmed: 36450604
Karikari TK, Pascoal TA, Ashton NJ et al (2020) 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 19:422–433. https://doi.org/10.1016/S1474-4422(20)30071-5
doi: 10.1016/S1474-4422(20)30071-5
pubmed: 32333900
Moscoso A, Grothe MJ, Ashton NJ et al (2021) Longitudinal associations of blood phosphorylated tau181 and neurofilament light chain with neurodegeneration in Alzheimer disease. JAMA Neurol 78:396–406. https://doi.org/10.1001/jamaneurol.2020.4986
doi: 10.1001/jamaneurol.2020.4986
pubmed: 33427873
Mielke MM, Dage JL, Frank RD et al (2022) Performance of plasma phosphorylated tau 181 and 217 in the community. Nat Med 28:1398–1405. https://doi.org/10.1038/s41591-022-01822-2
doi: 10.1038/s41591-022-01822-2
pubmed: 35618838
pmcid: 9329262
Planche V, Bouteloup V, Pellegrin I et al (2022) Validity and performance of blood biomarkers for Alzheimer disease to predict dementia risk in a large clinic-based cohort. Neurology. https://doi.org/10.1212/WNL.0000000000201479
doi: 10.1212/WNL.0000000000201479
pubmed: 36261295
Altomare D, Stampacchia S, Ribaldi F et al (2023) Plasma biomarkers for Alzheimer’s disease: a field-test in a memory clinic. J Neurol Neurosurg Psychiatry 94:420–427. https://doi.org/10.1136/jnnp-2022-330619
doi: 10.1136/jnnp-2022-330619
pubmed: 37012066
Mattsson-Carlgren N, Salvadó G, Ashton NJ et al (2023) Prediction of longitudinal cognitive decline in preclinical Alzheimer disease using plasma biomarkers. JAMA Neurol 80:360–369. https://doi.org/10.1001/jamaneurol.2022.5272
doi: 10.1001/jamaneurol.2022.5272
pubmed: 36745413
pmcid: 10087054
Jack CR, Wiste HJ, Algeciras-Schimnich A et al (2023) Predicting amyloid PET and tau PET stages with plasma biomarkers. Brain 146:2029–2044. https://doi.org/10.1093/brain/awad042
doi: 10.1093/brain/awad042
pubmed: 36789483
pmcid: 10151195
Janelidze S, Palmqvist S, Leuzy A et al (2022) Detecting amyloid positivity in early Alzheimer’s disease using combinations of plasma Aβ42/Aβ40 and p-tau. Alzheimer’s Dement 18:283–293. https://doi.org/10.1002/alz.12395
doi: 10.1002/alz.12395
Chouliaras L, Thomas A, Malpetti M et al (2022) Differential levels of plasma biomarkers of neurodegeneration in Lewy body dementia, Alzheimer’s disease, frontotemporal dementia and progressive supranuclear palsy. J Neurol Neurosurg Psychiatry. https://doi.org/10.1136/jnnp-2021-327788
doi: 10.1136/jnnp-2021-327788
pubmed: 35078917
Bellaver B, Povala G, Ferreira PCL et al (2023) Astrocyte reactivity influences amyloid-β effects on tau pathology in preclinical Alzheimer’s disease. Nat Med. https://doi.org/10.1038/s41591-023-02380-x
doi: 10.1038/s41591-023-02380-x
pubmed: 37248300
pmcid: 10353939
Ebenau JL, Pelkmans W, Verberk IMW et al (2022) Association of CSF, plasma, and imaging markers of neurodegeneration with clinical progression in people with subjective cognitive decline. Neurology. https://doi.org/10.1212/WNL.0000000000200035
doi: 10.1212/WNL.0000000000200035
pubmed: 35110378
pmcid: 8967429
Cousins KAQ, Shaw LM, Chen-Plotkin A et al (2022) Distinguishing frontotemporal lobar degeneration tau from TDP-43 using plasma biomarkers. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2022.3265
doi: 10.1001/jamaneurol.2022.3265
pubmed: 36215050
pmcid: 9552044
Benedet AL, Milà-Alomà M, Vrillon A et al (2021) Differences between plasma and cerebrospinal fluid glial fibrillary acidic protein levels across the Alzheimer disease continuum. JAMA Neurol 78:1471–1483. https://doi.org/10.1001/jamaneurol.2021.3671
doi: 10.1001/jamaneurol.2021.3671
pubmed: 34661615
del Campo M, Zetterberg H, Gandy S et al (2022) New developments of biofluid-based biomarkers for routine diagnosis and disease trajectories in frontotemporal dementia. Alzheimer’s Dement. https://doi.org/10.1002/alz.12643
doi: 10.1002/alz.12643
Mok TH, Nihat A, Majbour N et al (2023) Seed amplification and neurodegeneration marker trajectories in individuals at risk of prion disease. Brain 146:2570–2583. https://doi.org/10.1093/brain/awad101
doi: 10.1093/brain/awad101
pubmed: 36975162
pmcid: 10232278
Ashton NJ, Janelidze S, Al Khleifat A et al (2021) A multicentre validation study of the diagnostic value of plasma neurofilament light. Nat Commun. https://doi.org/10.1038/s41467-021-23620-z
doi: 10.1038/s41467-021-23620-z
pubmed: 34262030
pmcid: 8280160
O’Bryant SE, Petersen M, Hall J, Johnson LA (2022) Medical comorbidities and ethnicity impact plasma Alzheimer’s disease biomarkers: important considerations for clinical trials and practice. Alzheimer’s Dement. https://doi.org/10.1002/alz.12647
doi: 10.1002/alz.12647
Tsiknia AA, Edland SD, Sundermann EE et al (2022) Sex differences in plasma p-tau181 associations with Alzheimer’s disease biomarkers, cognitive decline, and clinical progression. Mol Psychiatry. https://doi.org/10.1038/s41380-022-01675-8
doi: 10.1038/s41380-022-01675-8
pubmed: 35768637
pmcid: 9718670
Syrjanen JA, Campbell MR, Algeciras-Schimnich A et al (2022) Associations of amyloid and neurodegeneration plasma biomarkers with comorbidities. Alzheimer’s Dement 18:1128–1140. https://doi.org/10.1002/alz.12466
doi: 10.1002/alz.12466
Dittrich A, Ashton NJ, Zetterberg H et al (2023) Association of chronic kidney disease with plasma NfL and other biomarkers of neurodegeneration: the H70 Birth Cohort Study in Gothenburg. Neurology. https://doi.org/10.1212/wnl.0000000000207419
doi: 10.1212/wnl.0000000000207419
pubmed: 37476021
pmcid: 10382262
Malek-Ahmadi M, Su Y, Ghisays V et al (2023) Plasma NfL is associated with the APOE ε4 allele, brain imaging measurements of neurodegeneration, and lower recall memory scores in cognitively unimpaired late-middle-aged and older adults. Alzheimer’s Res Ther 15:1–10. https://doi.org/10.1186/s13195-023-01221-w
doi: 10.1186/s13195-023-01221-w
Lehmann S, Schraen-Maschke S, Vidal J-S et al (2023) Plasma phosphorylated tau 181 predicts amyloid status and conversion to dementia stage dependent on renal function. J Neurol Neurosurg Psychiatry 94:411–419. https://doi.org/10.1136/jnnp-2022-330540
doi: 10.1136/jnnp-2022-330540
pubmed: 37012068
Zhang B, Zhang C, Wang Y et al (2023) Effect of renal function on the diagnostic performance of plasma biomarkers for Alzheimer’s disease. Front Aging Neurosci. https://doi.org/10.3389/fnagi.2023.1150510
doi: 10.3389/fnagi.2023.1150510
pubmed: 38131009
pmcid: 10722415
Janelidze S, Barthélemy NR, He Y et al (2023) Mitigating the associations of kidney dysfunction with blood biomarkers of Alzheimer disease by using phosphorylated tau to total tau ratios. JAMA Neurol. https://doi.org/10.1001/jamaneurol.2023.0199
doi: 10.1001/jamaneurol.2023.0199
pubmed: 38048096
pmcid: 10061310
Pichet Binette A, Janelidze S, Cullen N et al (2022) Confounding factors of Alzheimer’s disease plasma biomarkers and their impact on clinical performance. Alzheimer’s Dement. https://doi.org/10.1002/alz.12787
doi: 10.1002/alz.12787
Berry K, Asken BM, Grab JD et al (2022) Hepatic and renal function impact concentrations of plasma biomarkers of neuropathology. Alzheimer’s Dement Diagnosis Assess Dis Monit. https://doi.org/10.1002/dad2.12321
doi: 10.1002/dad2.12321
Rebelos E, Rissanen E, Bucci M et al (2022) Circulating neurofilament is linked with morbid obesity, renal function, and brain density. Sci Rep 12:1–10. https://doi.org/10.1038/s41598-022-11557-2
doi: 10.1038/s41598-022-11557-2
McKhann G (2011) 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 7:263–269. https://doi.org/10.1016/j.jalz.2011.03.005.The
doi: 10.1016/j.jalz.2011.03.005.The
pubmed: 21514250
pmcid: 3312024
Albert MS, DeKosky ST, Dickson D et al (2011) 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. Alzheimer’s Dement 11:96–106. https://doi.org/10.1176/appi.focus.11.1.96
doi: 10.1176/appi.focus.11.1.96
McKeith IG, Boeve BF, Dickson DW et al (2017) Diagnosis and management of dementia with Lewy bodies. Neurology 89:88–100. https://doi.org/10.1212/WNL.0000000000004058
doi: 10.1212/WNL.0000000000004058
pubmed: 28592453
pmcid: 5496518
Rascovsky K, Hodges JR, Knopman D et al (2011) Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain 134:2456–2477. https://doi.org/10.1093/brain/awr179
doi: 10.1093/brain/awr179
pubmed: 21810890
pmcid: 3170532
Höglinger GU, Respondek G, Stamelou M et al (2017) Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria. Mov Disord 32:853–864. https://doi.org/10.1002/mds.26987
doi: 10.1002/mds.26987
pubmed: 28467028
pmcid: 5516529
Armstrong MJ, Litvan I, Lang AE et al (2013) Criteria for the diagnosis of corticobasal degeneration. Neurology 80:496–503. https://doi.org/10.1212/WNL.0b013e31827f0fd1
doi: 10.1212/WNL.0b013e31827f0fd1
pubmed: 23359374
pmcid: 3590050
Gorno-Tempini ML, Hillis AE, Weintraub S et al (2011) Classification of primary progressive aphasia and its variants. Neurology 76:1006–1014. https://doi.org/10.1212/WNL.0b013e31821103e6
doi: 10.1212/WNL.0b013e31821103e6
pubmed: 21325651
pmcid: 3059138
Charlson ME, Pompei P, Ales KL, MacKenzie CR (1987) A new method of classifying prognostic comorbidity in longitudinal studies: Development and validation. J Chronic Dis 40:373–383. https://doi.org/10.1016/0021-9681(87)90171-8
doi: 10.1016/0021-9681(87)90171-8
pubmed: 3558716
Ramanan VK, Graff-Radford J, Syrjanen J et al (2023) Association of plasma biomarkers of Alzheimer disease with cognition and medical comorbidities in a biracial cohort. Neurology. https://doi.org/10.1212/WNL.0000000000207675
doi: 10.1212/WNL.0000000000207675
pubmed: 37586881
pmcid: 10356132
Brickman AM, Manly JJ, Honig LS et al (2021) Plasma p-tau181, p-tau217, and other blood-based Alzheimer’s disease biomarkers in a multi-ethnic, community study. Alzheimer’s Dement 17:1353–1364. https://doi.org/10.1002/alz.12301
doi: 10.1002/alz.12301
Vermunt L, Otte M, Verberk IMW et al (2022) Age- and disease-specific reference values for neurofilament light presented in an online interactive support interface. Ann Clin Transl Neurol 9:1832–1837. https://doi.org/10.1002/acn3.51676
doi: 10.1002/acn3.51676
pubmed: 36196979
pmcid: 9639622