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Preclinical amyloid-β and axonal degeneration pathology in delirium

Idland, Ane Victoria; Wyller, Torgeir Bruun; Stoen, Randi; Eri, Lars Magne; Frihagen, Frede; Ræder, Johan; Chaudhry, Farrukh Abbas; Hansson, Oskar LU ; Zetterberg, Henrik and Blennow, Kaj, et al. (2016) In Journal of Alzheimer's Disease 55(1). p.371-379
Abstract

Background: The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. Objective: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. Methods: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon... (More)

Background: The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. Objective: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ42), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. Methods: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Aβ42, T-tau, and P-tau were analyzed. Results: In patients without dementia, we found lower CSF Aβ42 levels (median, 310ng/L versus 489ng/L, p=0.006), higher T-tau levels (median, 505ng/L versus 351ng/L, p=0.02), but no change in P-tau in patients who developed delirium (n=16) compared to those who remained lucid (n=49). Delirious patients also had lower ratios of Aβ42 to T-tau (p<0.001) and P-tau (p=0.001) relative to those without delirium. CSF Aβ42 and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n=54) and without delirium (n=10). Conclusion: The reduction in CSF Aβ42, indicating β-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology.

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published
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keywords
Alzheimer's disease, biomarkers, cerebrospinal fluid, delirium, dementia, physiopathology
in
Journal of Alzheimer's Disease
volume
55
issue
1
pages
9 pages
publisher
IOS Press
external identifiers
  • scopus:84994633792
  • wos:000387671600030
ISSN
1387-2877
DOI
10.3233/JAD-160461
language
English
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yes
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d2684b63-b658-4609-bb6e-14b88ece3eaa
date added to LUP
2016-12-05 10:10:54
date last changed
2017-09-10 05:12:40
@article{d2684b63-b658-4609-bb6e-14b88ece3eaa,
  abstract     = {<p>Background: The clinical relevance of brain β-amyloidosis in older adults without dementia is not established. As delirium and dementia are strongly related, studies on patients with delirium may give pathophysiological clues. Objective: To determine whether the Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers amyloid-β 1-42 (Aβ<sub>42</sub>), total tau (T-tau), and phosphorylated tau (P-tau) are associated with delirium in hip fracture patients with and without dementia. Methods: CSF was collected in conjunction to spinal anesthesia in 129 patients. Delirium was assessed using the Confusion Assessment Method once daily in all patients, both pre- and postoperatively. The diagnosis of dementia at admission was based upon clinical consensus. CSF levels of Aβ<sub>42</sub>, T-tau, and P-tau were analyzed. Results: In patients without dementia, we found lower CSF Aβ<sub>42</sub> levels (median, 310ng/L versus 489ng/L, p=0.006), higher T-tau levels (median, 505ng/L versus 351ng/L, p=0.02), but no change in P-tau in patients who developed delirium (n=16) compared to those who remained lucid (n=49). Delirious patients also had lower ratios of Aβ<sub>42</sub> to T-tau (p&lt;0.001) and P-tau (p=0.001) relative to those without delirium. CSF Aβ<sub>42</sub> and T-tau remained significantly associated with delirium status in adjusted analyses. In patients with dementia, CSF biomarker levels did not differ between those with (n=54) and without delirium (n=10). Conclusion: The reduction in CSF Aβ<sub>42</sub>, indicating β-amyloidosis, and increase in T-tau, indicating neurodegeneration, in hip fracture patients without dementia developing delirium indicates that preclinical AD brain pathology is clinically relevant and possibly plays a role in delirium pathophysiology.</p>},
  author       = {Idland, Ane Victoria and Wyller, Torgeir Bruun and Stoen, Randi and Eri, Lars Magne and Frihagen, Frede and Ræder, Johan and Chaudhry, Farrukh Abbas and Hansson, Oskar and Zetterberg, Henrik and Blennow, Kaj and Bogdanovic, Nenad and Brækhus, Anne and Watne, L.O.},
  issn         = {1387-2877},
  keyword      = {Alzheimer's disease,biomarkers,cerebrospinal fluid,delirium,dementia,physiopathology},
  language     = {eng},
  number       = {1},
  pages        = {371--379},
  publisher    = {IOS Press},
  series       = {Journal of Alzheimer's Disease},
  title        = {Preclinical amyloid-β and axonal degeneration pathology in delirium},
  url          = {http://dx.doi.org/10.3233/JAD-160461},
  volume       = {55},
  year         = {2016},
}