Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium

Idland, Ane‐Victoria; Wyller, Torgeir Bruun; Støen, Randi; Eri, Lars M.; Frihagen, Frede; Ræder, Johan; Chaudhry, Farrukh A.; Hansson, Oskar; Zetterberg, Henrik; Blennow, Kaj; Bogdanović, Nenad; Brækhus, Anne; Watne, Leiv Otto

doi:10.3233/jad-160461

Cited by 40 publications

(70 citation statements)

References 504 publications

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“…Dementia is one of the strongest risk factors for delirium (Ahmed et al, ; Fong et al, ). However, of the three studies that examined whether levels of established CSF markers for dementia were associated with risk of delirium only Idland et al showed a convincing relationship (Idland et al, ). These findings may be related to the presence of incipient dementia, and future studies should take this into account.…”

Section: Discussionmentioning

confidence: 99%

“…Idland et al () also studied hip fracture patients. They found that, in patients without dementia, delirium was associated with lower CSF Aβ42 levels and higher t‐tau levels and lower ratios of Aβ42 to t‐tau and p‐tau.…”

Section: Risk Markers Of Deliriummentioning

confidence: 99%

“…There were no statistically significant differences in levels of these markers between those with or without post-operative delirium (preoperative delirium was excluded). Idland et al (2017) also studied hip fracture patients. They found that, in patients without dementia, delirium was associated with lower CSF Aβ42 levels and higher t-tau levels and lower ratios of Aβ42 to t-tau and p-tau.…”

Section: Dementia Neuropathology Markersmentioning

confidence: 99%

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CSF biomarkers in delirium: a systematic review

Hall

Watne

Cunningham³

et al. 2017

Int J Geriat Psychiatry

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Key points:1. Delirium is a major public health concern, and research on pathophysiological mechanisms is urgently needed.2. Some biochemical changes in the brain are to an extent reflected in the cerebrospinal fluid (CSF) and in recent years there has been a blossoming of studies examining CSF as a method of studying the pathophysiology of delirium.3. The 22 studies identified in this review reveal a small but growing literature, in which many of the important hypotheses in delirium pathogenesis have been examined, but from which few firm conclusions can currently be drawn. Nevertheless, the overall interpretation of the literature supports the vulnerable brain concept. 4. A concerted effort is now required to standardise several aspects of the methodology and reporting of these studies, in order to advance this highly promising direction in delirium research. Funding: The Norwegian Association for Public Health AbstractObjective In recent years there has been a blossoming of studies examining cerebrospinal fluid (CSF) as a method of studying the pathophysiology of delirium. We systematically reviewed the literature for CSF studies in delirium and provide here a summary of the implications for our understanding of delirium pathophysiology. We also summarise the methods used for CSF analysis and discuss challenges and implications for future studies.Methods In this systematic review we screened MEDLINE, EMBASE, PsycINFO, Web of Science, PubMed and the Cochrane Library for articles on CSF biomarkers in delirium, published to September 3 rd 2016. Studies were required to use DSM or ICD criteria for delirium, or a validated tool. We excluded case reports. There were no other restrictions on study type. ResultsWe identified 3280 articles from our initial search and 22 articles were included in this review. All studies were prospective, including over 400 patients with delirium and 700 controls. More than 70 different biomarkers were studied. Studies could not be compared with each other for meta-analysis because of their heterogeneity, and varied widely in their risk of bias and quality assessments. ConclusionsThe 22 studies identified in this review reveal a small but growing literature, in which many of the important hypotheses in delirium pathogenesis have been examined, but from which few firm conclusions can currently be drawn. Nevertheless, the overall interpretation of the literature supports the vulnerable brain concept, that is that biomarker 4 evidence of for example Alzheimer's disease pathology and/or neuroinflammation is associated with delirium.

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Section: Discussionmentioning

confidence: 99%

Section: Risk Markers Of Deliriummentioning

confidence: 99%

Section: Dementia Neuropathology Markersmentioning

confidence: 99%

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CSF biomarkers in delirium: a systematic review

Hall

Watne

Cunningham³

et al. 2017

Int J Geriat Psychiatry

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“…Several studies have associated the “CSF-AD signature” described above with delirium. Patients with post-operative delirium have a reduced CSF Aβ42/Tau ratio 15 and a recent study 16 found patients without dementia who developed delirium had lower CSF Aβ42 levels, higher T-tau levels, and lower ratios of Aβ42 to T-tau and P-tau relative to those without delirium. In contrast, other studies did not find significant differences between preoperative CSF Abeta1β42, tau, and P-tau levels in participants who did and did not develop delirium 17 .…”

Section: Ad Biomarkers and Deliriummentioning

confidence: 92%

Delirium and Alzheimer disease: A proposed model for shared pathophysiology

Fong

Vasunilashorn

Libermann

et al. 2019

Int J Geriat Psychiatry

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“…In individuals without dementia, some studies have reported an association between cerebrospinal fluid (CSF) or plasma levels of Aβ and tau and delirium (Idland et al, 2016; van den Boogaard et al, 2011; Xie et al, 2014) while others have not (Witlox et al, 2011). Similarly, some magnetic resonance imaging (MRI) studies of regional brain volume and delirium have identified an association (Gunther et al, 2012; Shioiri et al, 2016) while others have not (Cavallari et al, 2015; Root et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Alzheimer's-related cortical atrophy is associated with postoperative delirium severity in persons without dementia

Racine

Fong

Travison

et al. 2017

Neurobiology of Aging

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Patients with dementia due to Alzheimer’s disease (AD) have increased risk of developing delirium. This study investigated the relationship between a magnetic resonance imaging (MRI)-derived biomarker associated with preclinical AD and postoperative delirium. Participants were older adults (≥70 years) without dementia who underwent preoperative MRI and elective surgery. Delirium incidence and severity were evaluated daily during hospitalization. Cortical thickness was averaged across a published set of a priori brain regions to derive a measure known as the “AD signature.” Logistic and linear regression was used, respectively, to test whether the AD signature was associated with delirium incidence in the entire sample (N=145) or with the severity of delirium among those who developed delirium (N=32). Thinner cortex in the AD signature did not predict incidence of delirium (odds ratio=1.15, p=.38), but was associated with greater delirium severity among those who developed delirium (b=−1.2, p=.014). These results suggest that thinner cortices, perhaps reflecting underlying neurodegeneration due to preclinical AD, may serve as a vulnerability factor that increases severity once delirium occurs.

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Preclinical Amyloid-β and Axonal Degeneration Pathology in Delirium

Cited by 40 publications

References 504 publications

CSF biomarkers in delirium: a systematic review

CSF biomarkers in delirium: a systematic review

Delirium and Alzheimer disease: A proposed model for shared pathophysiology

Alzheimer's-related cortical atrophy is associated with postoperative delirium severity in persons without dementia

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