Association of CSF, Plasma, and Imaging Markers of Neurodegeneration With Clinical Progression in People With Subjective Cognitive Decline.

Autor:	Ebenau JL; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK. j.ebenau@amsterdamumc.nl., Pelkmans W; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Verberk IMW; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Verfaillie SCJ; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., van den Bosch KA; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., van Leeuwenstijn M; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Collij LE; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Scheltens P; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Prins ND; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Barkhof F; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., van Berckel BNM; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., Teunissen CE; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK., van der Flier WM; From the Alzheimer Center, Departments of Neurology (J.L.E., W.P., I.M.W.V., K.A.v.d.B., M.v.L., P.S., N.D.P., B.N.M.v.B., W.M.V.d.F.) and Radiology & Nuclear Medicine (S.C.J.V., L.E.C., F.B., B.N.M.v.B.), Amsterdam Neuroscience, and Neurochemistry Laboratory, Department of Clinical Chemistry (I.M.W.V., C.E.T.), and Department of Epidemiology & Biostatistics (W.M.v.d.F.), Vrije Universiteit Amsterdam, Amsterdam UMC, the Netherlands; and UCL Institutes of Neurology and Healthcare Engineering (F.B.), London, UK.
Jazyk:	angličtina
Zdroj:	Neurology [Neurology] 2022 Mar 29; Vol. 98 (13), pp. e1315-e1326. Date of Electronic Publication: 2022 Feb 02.
DOI:	10.1212/WNL.0000000000200035
Abstrakt:	Background and Objectives: Multiple biomarkers have been suggested to measure neurodegeneration (N) in the AT(N) framework, leading to inconsistencies between studies. We investigated the association of 5 N biomarkers with clinical progression and cognitive decline in individuals with subjective cognitive decline (SCD). Methods: We included individuals with SCD from the Amsterdam Dementia Cohort and SCIENCe project, a longitudinal cohort study (follow-up 4±3 years). We used the following N biomarkers: CSF total tau (t-tau), medial temporal atrophy visual rating on MRI, hippocampal volume (HV), serum neurofilament light (NfL), and serum glial fibrillary acidic protein (GFAP). We determined correlations between biomarkers. We assessed associations between N biomarkers and clinical progression to mild cognitive impairment or dementia (Cox regression) and Mini-Mental State Examination (MMSE) over time (linear mixed models). Models included age, sex, CSF β-amyloid (Aβ) (A), and CSF p-tau (T) as covariates, in addition to the N biomarker. Result: We included 401 individuals (61±9 years, 42% female, MMSE 28 ± 2, vascular comorbidities 8%-19%). N biomarkers were modestly to moderately correlated (range r -0.28 - 0.58). Serum NfL and GFAP correlated most strongly ( r 0.58, p < 0.01). T-tau was strongly correlated with p-tau ( r 0.89, p < 0.01), although these biomarkers supposedly represent separate biomarker groups. All N biomarkers individually predicted clinical progression, but only HV, NfL, and GFAP added predictive value beyond Aβ and p-tau (hazard ratio 1.52 [95% CI 1.11-2.09]; 1.51 [1.05-2.17]; 1.50 [1.04-2.15]). T-tau, HV, and GFAP individually predicted MMSE slope (range β -0.17 to -0.11, p < 0.05), but only HV remained associated beyond Aβ and p-tau (β -0.13 [SE 0.04]; p < 0.05). Discussion: In cognitively unimpaired older adults, correlations between different N biomarkers were only moderate, indicating they reflect different aspects of neurodegeneration and should not be used interchangeably. T-tau was strongly associated with p-tau (T), which makes it less desirable to use as a measure for N. HV, NfL, and GFAP predicted clinical progression beyond A and T. Our results do not allow to choose one most suitable biomarker for N, but illustrate the added prognostic value of N beyond A and T. Classification of Evidence: This study provides Class II evidence that HV, NfL, and GFAP predicted clinical progression beyond A and T in individuals with SCD. (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu