eprintid: 10064481
rev_number: 20
eprint_status: archive
userid: 608
dir: disk0/10/06/44/81
datestamp: 2018-12-19 16:40:49
lastmod: 2021-10-01 23:50:43
status_changed: 2018-12-19 16:40:49
type: article
metadata_visibility: show
creators_name: Kern, S
creators_name: Syrjanen, JA
creators_name: Blennow, K
creators_name: Zetterberg, H
creators_name: Skoog, I
creators_name: Waern, M
creators_name: Hagen, CE
creators_name: van Harten, AC
creators_name: Knopman, DS
creators_name: Jack, CR
creators_name: Petersen, RC
creators_name: Mielke, MM
title: Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment
ispublished: inpress
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
divisions: F86
note: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
abstract: IMPORTANCE: Accumulating data suggest that elevated cerebrospinal fluid (CSF) neurofilament light (NfL) and neurogranin (Ng) levels are associated with cognitive decline and may be useful markers of neurodegeneration. However, to our knowledge, previous studies have not assessed these CSF markers in the community, evaluated them with regards to risk of mild cognitive impairment (MCI), or compared their prognostic value with CSF total tau (T-tau) or phosphorylated tau (P-tau). OBJECTIVE: To determine (1) whether CSF NfL and Ng levels were associated with risk of MCI, (2) the effect size of these markers compared with CSF T-tau or P-tau for risk of MCI, and (3) whether CSF amyloid-β (Aβ42) modified these associations. DESIGN, SETTING AND PARTICIPANTS: The analyses included 648 participants without cognitive impairment who were enrolled into the prospective population-based Mayo Clinic Study of Aging between January 2004 and December 2015 with available CSF data and at least 1 follow-up visit. Participants were followed up for a median of 3.8 years (interquartile range, 2.6-5.4 years). The CSF NfL and Ng levels were measured using an in-house sandwich enzyme-linked immunosorbent assay. The CSF Aβ42, T-tau, and P-tau levels were measured with automated electrochemiluminescence immunoassays. Cox proportional hazards models, with age as the timescale, were used to assess the association between CSF NfL, Ng, Aβ42, T-tau, or P-tau with risk of MCI after adjusting for sex, education, apolipoprotein E genotype, and the Charlson comorbidity index. To examine CSF Aβ42 as an effect modifier, it was categorized into tertiles; the bottom tertile was defined as having elevated brain amyloid. MAIN OUTCOMES AND MEASURES: Risk of MCI. RESULTS: At baseline, the median age of the 648 participants without cognitive impairment was 72.3 years (range, 50.7-95.3 years) and 366 (56.5%) were men; 96 (14.8%) developed incident MCI. Compared with the bottom quartile, the top quartile of CSF NfL was associated with a 3.1-fold increased risk of MCI (hazard ratio, 3.13; 95% CI, 1.36-7.18) in multivariate models. Neither CSF T-tau, P-tau, nor Ng was associated with risk of MCI. There was no interaction between Aβ42 and CSF NfL for risk of MCI. CONCLUSION AND RELEVANCE: Elevated CSF NfL levels but not CSF T-tau, P-tau or Ng are a risk factor for MCI in a community population and are independent of brain amyloid.
date: 2018-11-12
date_type: published
official_url: http://dx.doi.org/10.1001/jamaneurol.2018.3459
full_text_type: other
language: eng
article_type_text: Journal Article
verified: verified_manual
elements_id: 1601179
doi: 10.1001/jamaneurol.2018.3459
pii: 2712850
language_elements: English
lyricists_name: Zetterberg, Henrik
lyricists_id: HZETT94
actors_name: Zetterberg, Henrik
actors_name: Harriot, Anne-Marie
actors_id: HZETT94
actors_id: AHARA72
actors_role: owner
actors_role: impersonator
full_text_status: restricted
publication: JAMA Neurology
event_location: United States
issn: 2168-6149
citation:        Kern, S;    Syrjanen, JA;    Blennow, K;    Zetterberg, H;    Skoog, I;    Waern, M;    Hagen, CE;                     ... Mielke, MM; + view all <#>        Kern, S;  Syrjanen, JA;  Blennow, K;  Zetterberg, H;  Skoog, I;  Waern, M;  Hagen, CE;  van Harten, AC;  Knopman, DS;  Jack, CR;  Petersen, RC;  Mielke, MM;   - view fewer <#>    (2018)    Association of Cerebrospinal Fluid Neurofilament Light Protein With Risk of Mild Cognitive Impairment Among Individuals Without Cognitive Impairment.                   JAMA Neurology        10.1001/jamaneurol.2018.3459 <https://doi.org/10.1001/jamaneurol.2018.3459>.    (In press).   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10064481/1/Zetterberg_Association%20of%20Cerebrospinal%20Fluid%20Neurofilament%20Light%20Protein%20With%20Risk%20of%20Mild%20Cognitive%20Impairment%20Among%20Individuals%20Without%20Cognitive%20Impairment_AAM.pdf