Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium.
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.



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.



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.



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).



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.
Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway.
Ane-Victoria
AV
Idland
Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.
Torgeir Bruun
TB
Wyller
Department of Anesthesiology, Oslo University Hospital, Oslo, Norway.
Randi
R
Støen
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Urology, Oslo University Hospital, Oslo, Norway.
Lars Magne
LM
Eri
Department of Orthopedic Surgery, Oslo University Hospital, Oslo, Norway.
Frede
F
Frihagen
Department of Anesthesiology, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Johan
J
Ræder
Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Farrukh Abbas
FA
Chaudhry
Department of Clinical Sciences, Lund University, Lund, Sweden.|Memory Clinic, Skåne University Hospital, Lund, Sweden.
Oskar
O
Hansson
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.|Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
Henrik
H
Zetterberg
Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
Kaj
K
Blennow
Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Nenad
N
Bogdanovic
Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway.|Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tberg, Tønsnerg, Norway.
Anne
A
Brækhus
Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Leiv Otto
LO
Watne
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid; D003693:Delirium / Q000134:cerebrospinal fluid* / Q000209:etiology / Q000628:therapy; D003704:Dementia / Q000134:cerebrospinal fluid / Q000150:complications; D005260:Female; D006620:Hip Fractures / Q000134:cerebrospinal fluid / Q000150:complications / Q000601:surgery; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010446:Peptide Fragments / Q000134:cerebrospinal fluid*; D010766:Phosphorylation; D016896:Treatment Outcome; D016875:tau Proteins / Q000134:cerebrospinal fluid
D016229:Amyloid beta-Peptides; D015415:Biomarkers; C054369:MAPT protein, human; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins
Alzheimer’s disease; biomarkers; cerebrospinal fluid; delirium; dementia; physiopathology