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Proinflammatory cytokines, sickness behavior, and Alzheimer disease

Proinflammatory cytokines, sickness behavior, and Alzheimer disease
Proinflammatory cytokines, sickness behavior, and Alzheimer disease


Background: In Alzheimer disease (AD), systemic inflammation is known to give rise to a delirium. However, systemic inflammation also gives rise to other centrally mediated symptoms in the absence of a delirium, a concept known as sickness behavior. Systemic inflammation is characterized by the systemic production of the proinflammatory cytokines tumor necrosis factor–? (TNF?) and interleukin-6 (IL-6) that mediate immune to brain communication and the development of sickness behavior.

Objective: To determine if raised serum TNF? or IL-6 are associated with the presence of sickness behavior symptoms, independent of the development of delirium, in a prospective cohort study of subjects with AD.

Methods: A total of 300 subjects with mild to severe AD were cognitively assessed at baseline and a blood sample taken for inflammatory markers. Cognitive assessments, including assessments to detect the development of a delirium, and blood samples were repeated at 2, 4, and 6 months. The development of neuropsychiatric symptoms in the subject with AD over the 6-month follow-up period was assessed independently by carer interview at 2, 4, and 6 months.

Results: Raised serum TNF? and IL-6, but not CRP, were associated with an approximately 2-fold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior. These relationships are independent of the development of delirium.

Conclusions: Increased serum proinflammatory cytokines are associated with the presence of symptoms characteristic of sickness behavior, which are common neuropsychiatric features found in AD. This association was independent of the presence of delirium.
0028-3878
212-218
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Zotova, E.
3558dd45-67a7-4e7a-b2ef-a9155ca784e8
Culliford, D.
25511573-74d3-422a-b0ee-dfe60f80df87
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Zotova, E.
3558dd45-67a7-4e7a-b2ef-a9155ca784e8
Culliford, D.
25511573-74d3-422a-b0ee-dfe60f80df87
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Holmes, C., Cunningham, C., Zotova, E., Culliford, D. and Perry, V.H. (2011) Proinflammatory cytokines, sickness behavior, and Alzheimer disease. Neurology, 77 (3), 212-218. (doi:10.1212/WNL.0b013e318225ae07). (PMID:21753171)

Record type: Article

Abstract



Background: In Alzheimer disease (AD), systemic inflammation is known to give rise to a delirium. However, systemic inflammation also gives rise to other centrally mediated symptoms in the absence of a delirium, a concept known as sickness behavior. Systemic inflammation is characterized by the systemic production of the proinflammatory cytokines tumor necrosis factor–? (TNF?) and interleukin-6 (IL-6) that mediate immune to brain communication and the development of sickness behavior.

Objective: To determine if raised serum TNF? or IL-6 are associated with the presence of sickness behavior symptoms, independent of the development of delirium, in a prospective cohort study of subjects with AD.

Methods: A total of 300 subjects with mild to severe AD were cognitively assessed at baseline and a blood sample taken for inflammatory markers. Cognitive assessments, including assessments to detect the development of a delirium, and blood samples were repeated at 2, 4, and 6 months. The development of neuropsychiatric symptoms in the subject with AD over the 6-month follow-up period was assessed independently by carer interview at 2, 4, and 6 months.

Results: Raised serum TNF? and IL-6, but not CRP, were associated with an approximately 2-fold increased frequency of neuropsychiatric symptoms characteristic of sickness behavior. These relationships are independent of the development of delirium.

Conclusions: Increased serum proinflammatory cytokines are associated with the presence of symptoms characteristic of sickness behavior, which are common neuropsychiatric features found in AD. This association was independent of the presence of delirium.

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More information

Published date: 19 July 2011
Organisations: Primary Care & Population Sciences, Clinical & Experimental Sciences

Identifiers

Local EPrints ID: 337607
URI: http://eprints.soton.ac.uk/id/eprint/337607
ISSN: 0028-3878
PURE UUID: f1dd6023-3d5d-4cdf-b0d0-4026bfcbab98
ORCID for C. Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for D. Culliford: ORCID iD orcid.org/0000-0003-1663-0253

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Date deposited: 01 May 2012 09:37
Last modified: 15 Mar 2024 03:19

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Contributors

Author: C. Holmes ORCID iD
Author: C. Cunningham
Author: E. Zotova
Author: D. Culliford ORCID iD
Author: V.H. Perry

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