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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–α (TNFα) and interleukin-6 (IL-6) that mediate immune to brain communication and the development of sickness behavior.
Objective: To determine if raised serum TNFα 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 TNFα 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.
Footnotes
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Study funding: Supported by the UK Alzheimer's Society.
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- AD=
- Alzheimer disease;
- ADAS-Cog=
- Alzheimer's Disease Assessment Scale Cognitive subscale;
- CAM=
- Confusion Assessment Method;
- CheI=
- cholinesterase inhibitor;
- CI=
- confidence interval;
- CRP=
- C-reactive protein;
- DSM-III-R=
- Diagnostic and Statistical Manual of Mental Disorders, 3rd edition, revised;
- DSM-IV=
- Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
- IL-6=
- interleukin-6;
- IQR=
- interquartile range;
- MSD=
- Meso Scale Discovery;
- NINCDS-ADRDA=
- Neurological and Communicative Disorders and Stroke–Alzheimer's Disease and Related Disorders Association;
- NPI=
- Neuropsychiatric Inventory;
- OR=
- odds ratio;
- SIE=
- systemic inflammatory event;
- TNFα=
- tumor necrosis factor–α.
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Editorial, page 206
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Supplemental data at www.neurology.org
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- Received July 23, 2010.
- Accepted December 22, 2010.
- Copyright © 2011 by AAN Enterprises, Inc.
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