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Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients : A multi-cohort study

Salvadó, Gemma LU ; Larsson, Victoria LU ; Cody, Karly A. ; Cullen, Nicholas C. LU ; Jonaitis, Erin M. ; Stomrud, Erik LU orcid ; Kollmorgen, Gwendlyn ; Wild, Norbert ; Palmqvist, Sebastian LU orcid and Janelidze, Shorena LU , et al. (2023) In Alzheimer's and Dementia 19(7). p.2943-2955
Abstract

Introduction: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases. Methods: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of Aβ42, Aβ40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, α-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit). Results: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU)... (More)

Introduction: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases. Methods: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of Aβ42, Aβ40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, α-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit). Results: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/Aβ42 alone (R2 ≥ 0.31) or together with NfL (R2 = 0.25), while p-tau/Aβ42 (R2 ≥ 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/Aβ42 (AUC ≥ 0.87) and p-tau/Aβ42 together with NfL (AUC ≥ 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively. Discussion: P-tau/Aβ42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
amyloid-β, BioFINDER, cognitive decline, conversion to dementia, glial activation, inflammation, neurodegeneration, tau ratio, WADRC, WRAP
in
Alzheimer's and Dementia
volume
19
issue
7
pages
2943 - 2955
publisher
Wiley
external identifiers
  • scopus:85146317403
  • pmid:36648169
ISSN
1552-5260
DOI
10.1002/alz.12907
language
English
LU publication?
yes
id
a6738bbb-953f-4ebb-adb6-9e64c099fae0
date added to LUP
2023-02-15 11:06:59
date last changed
2024-06-13 23:59:50
@article{a6738bbb-953f-4ebb-adb6-9e64c099fae0,
  abstract     = {{<p>Introduction: Our objective was determining the optimal combinations of cerebrospinal fluid (CSF) biomarkers for predicting disease progression in Alzheimer's disease (AD) and other neurodegenerative diseases. Methods: We included 1,983 participants from three different cohorts with longitudinal cognitive and clinical data, and baseline CSF levels of Aβ42, Aβ40, phosphorylated tau at threonine-181 (p-tau), neurofilament light (NfL), neurogranin, α-synuclein, soluble triggering receptor expressed on myeloid cells 2 (sTREM2), glial fibrillary acidic protein (GFAP), YKL-40, S100b, and interleukin 6 (IL-6) (Elecsys NeuroToolKit). Results: Change of modified Preclinical Alzheimer's Cognitive Composite (mPACC) in cognitively unimpaired (CU) was best predicted by p-tau/Aβ42 alone (R<sup>2</sup> ≥ 0.31) or together with NfL (R<sup>2</sup> = 0.25), while p-tau/Aβ42 (R<sup>2</sup> ≥ 0.19) was sufficient to accurately predict change of the Mini-Mental State Examination (MMSE) in mild cognitive impairment (MCI) patients. P-tau/Aβ42 (AUC ≥ 0.87) and p-tau/Aβ42 together with NfL (AUC ≥ 0.75) were the best predictors of conversion to AD and all-cause dementia, respectively. Discussion: P-tau/Aβ42 is sufficient for predicting progression in AD, with very high accuracy. Adding NfL improves the prediction of all-cause dementia conversion and cognitive decline.</p>}},
  author       = {{Salvadó, Gemma and Larsson, Victoria and Cody, Karly A. and Cullen, Nicholas C. and Jonaitis, Erin M. and Stomrud, Erik and Kollmorgen, Gwendlyn and Wild, Norbert and Palmqvist, Sebastian and Janelidze, Shorena and Mattsson-Carlgren, Niklas and Zetterberg, Henrik and Blennow, Kaj and Johnson, Sterling C. and Ossenkoppele, Rik and Hansson, Oskar}},
  issn         = {{1552-5260}},
  keywords     = {{amyloid-β; BioFINDER; cognitive decline; conversion to dementia; glial activation; inflammation; neurodegeneration; tau ratio; WADRC; WRAP}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{2943--2955}},
  publisher    = {{Wiley}},
  series       = {{Alzheimer's and Dementia}},
  title        = {{Optimal combinations of CSF biomarkers for predicting cognitive decline and clinical conversion in cognitively unimpaired participants and mild cognitive impairment patients : A multi-cohort study}},
  url          = {{http://dx.doi.org/10.1002/alz.12907}},
  doi          = {{10.1002/alz.12907}},
  volume       = {{19}},
  year         = {{2023}},
}