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Systemic inflammation and delirium: important co-factors in the progression of dementia
Open accessAbstract
It is widely accepted that inflammation plays some role in the progression of chronic neurodegenerative diseases such as AD (Alzheimer's disease), but its precise role remains elusive. It has been known for many years that systemic inflammatory insults can signal to the brain to induce changes in CNS (central nervous system) function, typically grouped under the syndrome of sickness behaviour. These changes are mediated via systemic and CNS cytokine and prostaglandin synthesis. When patients with dementia suffer similar systemic inflammatory insults, delirium is a frequent consequence. This profound and acute exacerbation of cognitive dysfunction is associated with poor prognosis: accelerating cognitive decline and shortening time to permanent institutionalization and death. Therefore a better understanding of how delirium occurs during dementia and how these episodes impact on existing neurodegeneration are now important priorities. The current review summarizes the relationship between dementia, systemic inflammation and episodes of delirium and addresses the basic scientific approaches currently being pursued with respect to understanding acute cognitive dysfunction during aging and dementia. In addition, despite there being limited studies on this subject, it is becoming increasingly clear that infections and other systemic inflammatory conditions do increase the risk of AD and accelerate the progression of established dementia. These data suggest that systemic inflammation is a major contributor to the progression of dementia and constitutes an important clinical target.
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“Several hypotheses for its development have been proposed, such as the oxidative stress hypothesis 188 , the neuroinflammatory hypothesis 189 , the neuroendocrine hypothesis including the role of aberrant stress 190 , and the circadian rhythm dysregulation hypothesis 190 .”
From Mental health care for older adults: recent advances and new directions in clinical practice and research (2022) · cites this paper as [189]
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Metadata
- Authors
- Cunningham, C.
- Affiliations
- Trinity College Dublin (IE)
- Corresponding author
- Cunningham, Colm
- ORCID
- Cunningham, Colm
- Venue
- Biochemical Society Transactions
- Publisher
- Portland Press Ltd.
- Published
- 2011-07-20
- Volume
- 39
- Issue
- 4
- Pages
- 945-953
- ISSN
- 0300-5127 (ISSN-L)
- 1470-8752
- PMC
- PMC4157218
- OpenAlex
- W2105065969
- Cited by
- 153
- References
- 74
- Citations by year
- 2026: 13 · 2025: 7 · 2024: 4 · 2023: 11 · 2022: 13 · 2021: 16 · 2020: 17 · 2019: 8 · 2018: 9 · 2017: 10 · 2016: 5 · 2015: 7 · 2014: 9 · 2013: 10 · 2012: 12
- FWCI
- 0.93
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Biochemical Society Transactions (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Arrow@dit (Dublin Institute of Technology) (submittedVersion, cc-by-nc-sa)
- Trinity's Access to Research Output (TARA) (Trinity College Dublin) (submittedVersion)
- Funders
- Wellcome Trust (090907)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Critical Care and Intensive Care Medicine › Intensive Care Unit Cognitive Disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- systemic inflammation, delirium, dementia progression, Alzheimer's disease, sickness behavior, cytokines, prostaglandins, cognitive decline, infection, neurodegeneration, aging
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Central Nervous System, Delirium, Dementia, Humans, Inflammation, Disease Progression
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