Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium

J Alzheimers Dis. 2017;55(1):371-379. doi: 10.3233/JAD-160461.


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, 310 ng/L versus 489 ng/L, p = 0.006), higher T-tau levels (median, 505 ng/L versus 351 ng/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.

Keywords: Alzheimer’s disease; biomarkers; cerebrospinal fluid; delirium; dementia; physiopathology.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amyloid beta-Peptides / cerebrospinal fluid*
  • Biomarkers / cerebrospinal fluid
  • Delirium / cerebrospinal fluid*
  • Delirium / etiology
  • Delirium / therapy
  • Dementia / cerebrospinal fluid
  • Dementia / complications
  • Female
  • Hip Fractures / cerebrospinal fluid
  • Hip Fractures / complications
  • Hip Fractures / surgery
  • Humans
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Peptide Fragments / cerebrospinal fluid*
  • Phosphorylation
  • Treatment Outcome
  • tau Proteins / cerebrospinal fluid


  • Amyloid beta-Peptides
  • Biomarkers
  • MAPT protein, human
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • tau Proteins