Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium

Article type: Research Article

Authors: Idland, Ane-Victoria^{a; b; *} | Wyller, Torgeir Bruun^{a; c} | Støen, Randi^d | Eri, Lars Magne^{e; f} | Frihagen, Frede^g | Ræder, Johan^{d; e} | Chaudhry, Farrukh Abbas^h | Hansson, Oskar^{i; j} | Zetterberg, Henrik^{k; l} | Blennow, Kaj^k | Bogdanovic, Nenad^{c; e} | Brækhus, Anne^{c; m} | Watne, Leiv Otto^{a; h}

Affiliations: [a] Oslo Delirium Research Group, Department of Geriatric Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway | [b] Research Group for Lifespan Changes in Brain and Cognition, Department of Psychology, University of Oslo, Oslo, Norway | [c] Department of Geriatric Medicine, Oslo University Hospital, Oslo, Norway | [d] Department of Anesthesiology, Oslo University Hospital, Oslo, Norway | [e] Institute of Clinical Medicine, University of Oslo, Oslo, Norway | [f] Department of Urology, Oslo University Hospital, Oslo, Norway | [g] Department of Orthopedic Surgery, Oslo University Hospital, Oslo, Norway | [h] Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway | [i] Department of Clinical Sciences, Lund University, Lund, Sweden | [j] Memory Clinic, Skåne University Hospital, Lund, Sweden | [k] Clinical Neurochemistry Lab, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden | [l] Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK | [m] Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tberg, Tønsnerg, Norway

Correspondence: [*] Correspondence to: Ane-Victoria Idland, University of Oslo, Campus Ullevål, Department of Geriatric Medicine, PB 4956 Nydalen, 0424 Oslo, Norway. Tel.: +47 91881081; E-mail: [email protected].

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 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

DOI: 10.3233/JAD-160461

Journal: Journal of Alzheimer's Disease, vol. 55, no. 1, pp. 371-379, 2017