Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Cerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer's Disease

Wattmo, Carina LU ; Blennow, Kaj LU and Hansson, Oskar LU orcid (2021) In Current Alzheimer Research 18(7). p.573-584
Abstract

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer's disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results.

OBJECTIVE: We investigated potential relationships between CSF amyloid-β1-42 (Aβ42), phosphorylated tau (P-tau), and total tau (T-tau) with time to nursing home placement (NHP) and life expectancy after diagnosis.

METHODS: This prospective observational study included 129 outpatients clinically diagnosed with mild-to-moderate AD who underwent a lumbar puncture. The CSF biomarkers were analysed with xMAP technology. Dates of institutionalisation and death were recorded.

RESULTS: After... (More)

BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer's disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results.

OBJECTIVE: We investigated potential relationships between CSF amyloid-β1-42 (Aβ42), phosphorylated tau (P-tau), and total tau (T-tau) with time to nursing home placement (NHP) and life expectancy after diagnosis.

METHODS: This prospective observational study included 129 outpatients clinically diagnosed with mild-to-moderate AD who underwent a lumbar puncture. The CSF biomarkers were analysed with xMAP technology. Dates of institutionalisation and death were recorded.

RESULTS: After 20 years of follow-up, 123 patients (95%) were deceased. The participants with abnormal P-tau and T-tau (A+ T+ (N)+) died earlier than those with normal P-tau/abnormal T-tau (A+ T- (N)+) (mean, 80.5 vs. 85.4 years). Linear associations were demonstrated between lower Aβ42 and shorter time to NHP (p = 0.017), and higher P-tau and younger age at death (p = 0.016). No correlations were detected between survival after AD diagnosis and CSF biomarkers. In sex- and-age-adjusted Cox regression models, higher P-tau and T-tau were independent predictors of shorter lifespan after diagnosis. In multivariate Cox models, older age and lower baseline cognitive status, but not elevated tau, significantly precipitated both institutionalisation and death.

CONCLUSION: These findings suggest that CSF biomarker levels plateau in the dementia phase of AD, which may limit their possible relationships with clinical end-points, such as NHP and survival time. However, the biomarkers reflect the central pathophysiologies of AD. In particular, pathologic tau is associated with more advanced disease, younger age at onset, and earlier death.

(Less)
Please use this url to cite or link to this publication:
author
; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Current Alzheimer Research
volume
18
issue
7
pages
573 - 584
publisher
Bentham Science Publishers
external identifiers
  • pmid:34719365
  • scopus:85122546321
ISSN
1875-5828
DOI
10.2174/1567205018666211022164952
language
English
LU publication?
yes
id
9165161f-5d72-4a1f-8856-2e75c274926a
date added to LUP
2021-11-29 09:09:42
date last changed
2024-06-07 15:03:43
@article{9165161f-5d72-4a1f-8856-2e75c274926a,
  abstract     = {{<p>BACKGROUND: Cerebrospinal fluid (CSF) biomarkers are associated with conversion from mild cognitive impairment to Alzheimer's disease (AD), but their predictive value for later end-points has been less evaluated with inconsistent results.</p><p>OBJECTIVE: We investigated potential relationships between CSF amyloid-β1-42 (Aβ42), phosphorylated tau (P-tau), and total tau (T-tau) with time to nursing home placement (NHP) and life expectancy after diagnosis.</p><p>METHODS: This prospective observational study included 129 outpatients clinically diagnosed with mild-to-moderate AD who underwent a lumbar puncture. The CSF biomarkers were analysed with xMAP technology. Dates of institutionalisation and death were recorded.</p><p>RESULTS: After 20 years of follow-up, 123 patients (95%) were deceased. The participants with abnormal P-tau and T-tau (A+ T+ (N)+) died earlier than those with normal P-tau/abnormal T-tau (A+ T- (N)+) (mean, 80.5 vs. 85.4 years). Linear associations were demonstrated between lower Aβ42 and shorter time to NHP (p = 0.017), and higher P-tau and younger age at death (p = 0.016). No correlations were detected between survival after AD diagnosis and CSF biomarkers. In sex- and-age-adjusted Cox regression models, higher P-tau and T-tau were independent predictors of shorter lifespan after diagnosis. In multivariate Cox models, older age and lower baseline cognitive status, but not elevated tau, significantly precipitated both institutionalisation and death.</p><p>CONCLUSION: These findings suggest that CSF biomarker levels plateau in the dementia phase of AD, which may limit their possible relationships with clinical end-points, such as NHP and survival time. However, the biomarkers reflect the central pathophysiologies of AD. In particular, pathologic tau is associated with more advanced disease, younger age at onset, and earlier death.</p>}},
  author       = {{Wattmo, Carina and Blennow, Kaj and Hansson, Oskar}},
  issn         = {{1875-5828}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{573--584}},
  publisher    = {{Bentham Science Publishers}},
  series       = {{Current Alzheimer Research}},
  title        = {{Cerebrospinal Fluid Biomarker Levels as Markers for Nursing Home Placement and Survival Time in Alzheimer's Disease}},
  url          = {{https://lup.lub.lu.se/search/files/110315068/Wattmo_CSF_biomarkers_NHP_survival.pdf}},
  doi          = {{10.2174/1567205018666211022164952}},
  volume       = {{18}},
  year         = {{2021}},
}