Ebenau, Jarith L;
Pelkmans, Wiesje;
Verberk, Inge MW;
Verfaillie, Sander;
van den Bosch, Karlijn A;
van Leeuwenstijn, Mardou;
Collij, Lyduine;
... Van der Flier, Wiesje M; + view all
(2022)
Association of CSF, Plasma, and Imaging Markers of Neurodegeneration With Clinical Progression in People With Subjective Cognitive Decline.
Neurology
10.1212/WNL.0000000000200035.
(In press).
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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.
| Type: | Article |
|---|---|
| Title: | Association of CSF, Plasma, and Imaging Markers of Neurodegeneration With Clinical Progression in People With Subjective Cognitive Decline |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1212/WNL.0000000000200035 |
| Publisher version: | https://doi.org/10.1212/WNL.0000000000200035 |
| Language: | English |
| Additional information: | 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/ |
| UCL classification: | UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Brain Repair and Rehabilitation UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10143777 |
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