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Publication Detail
Association of CSF, Plasma, and Imaging Markers of Neurodegeneration With Clinical Progression in People With Subjective Cognitive Decline
  • Publication Type:
    Journal article
  • Authors:
    Ebenau JL, Pelkmans W, Verberk IMW, Verfaillie S, van den Bosch KA, van Leeuwenstijn M, Collij L, Scheltens P, Prins N, Barkhof F, van Berckel B, Teunissen CE, Van der Flier WM
  • Publisher:
    Ovid Technologies (Wolters Kluwer Health)
  • Publication date:
    02/02/2022
  • Journal:
    Neurology
  • Medium:
    Print-Electronic
  • Status:
    Accepted
  • Country:
    United States
  • PII:
    WNL.0000000000200035
  • Language:
    English
  • Notes:
    This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
Abstract
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 (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 MMSE over time (linear mixed models). Models included age and sex, CSF abeta (A), and CSF p-tau (T) as covariates, in addition to the N biomarker. RESULT: We included 401 individuals (61±9 years, 42%F, MMSE28 ± 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 abeta and p-tau (HR 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 beta -0.17 - -0.11, p < 0.05), but only HV remained associated beyond abeta and p-tau (beta -0.13 (SE 0.04), p < 0.05). DISCUSSION: In cognitively unimpaired elderly, 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 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.
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