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Systematic inflammation and disease progression in Alzheimer disease

Systematic inflammation and disease progression in Alzheimer disease
Systematic inflammation and disease progression in Alzheimer disease
Background: acute and chronic systemic inflammation are characterized by the systemic production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) that plays a role in immune to brain communication. Previous preclinical research shows that acute systemic inflammation contributes to an exacerbation of neurodegeneration by activation of primed microglial cells.

Objective: to determine whether acute episodes of systemic inflammation associated with increased TNF-alpha would be associated with long-term cognitive decline in a prospective cohort study of subjects with Alzheimer disease.

Methods: three hundred community-dwelling subjects with mild to severe Alzheimer disease were cognitively assessed, and a blood sample was taken for systemic inflammatory markers. Each subject's main caregiver was interviewed to assess the presence of incident systemic inflammatory events. Assessments of both patient and caregiver were repeated at 2, 4, and 6 months.

Results: acute systemic inflammatory events, found in around half of all subjects, were associated with an increase in the serum levels of proinflammatory cytokine TNF-alpha and a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF-alpha were associated with a 4-fold increase in the rate of cognitive decline. Subjects who had low levels of serum TNF-alpha throughout the study showed no cognitive decline over the 6-month period.

Conclusions: both acute and chronic systemic inflammation, associated with increases in serum tumor necrosis factor alpha, is associated with an increase in cognitive decline in Alzheimer disease.
0028-3878
768-774
Holmes, C.
ada5abf3-8459-4cf7-be40-3f4e9391cc96
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Zotova, E.
3558dd45-67a7-4e7a-b2ef-a9155ca784e8
Woolford, J.
b75c6a2d-471e-41e0-9fe2-a68970bdfa25
Dean, C.
e8916a16-074c-4b09-a261-7c397e37a11d
Kerr, S.
cf99a6d2-e5e4-4399-9eed-0a14e0a40587
Culliford, D.J.
25511573-74d3-422a-b0ee-dfe60f80df87
Perry, V.
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
Woolford, J.
b75c6a2d-471e-41e0-9fe2-a68970bdfa25
Dean, C.
e8916a16-074c-4b09-a261-7c397e37a11d
Kerr, S.
cf99a6d2-e5e4-4399-9eed-0a14e0a40587
Culliford, D.J.
25511573-74d3-422a-b0ee-dfe60f80df87
Perry, V.
8f29d36a-8e1f-4082-8700-09483bbaeae4

Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D.J. and Perry, V. (2009) Systematic inflammation and disease progression in Alzheimer disease. Neurology, 73 (10), 768-774. (doi:10.1212/WNL.0b013e3181b6bb95). (PMID:19738171)

Record type: Article

Abstract

Background: acute and chronic systemic inflammation are characterized by the systemic production of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha) that plays a role in immune to brain communication. Previous preclinical research shows that acute systemic inflammation contributes to an exacerbation of neurodegeneration by activation of primed microglial cells.

Objective: to determine whether acute episodes of systemic inflammation associated with increased TNF-alpha would be associated with long-term cognitive decline in a prospective cohort study of subjects with Alzheimer disease.

Methods: three hundred community-dwelling subjects with mild to severe Alzheimer disease were cognitively assessed, and a blood sample was taken for systemic inflammatory markers. Each subject's main caregiver was interviewed to assess the presence of incident systemic inflammatory events. Assessments of both patient and caregiver were repeated at 2, 4, and 6 months.

Results: acute systemic inflammatory events, found in around half of all subjects, were associated with an increase in the serum levels of proinflammatory cytokine TNF-alpha and a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF-alpha were associated with a 4-fold increase in the rate of cognitive decline. Subjects who had low levels of serum TNF-alpha throughout the study showed no cognitive decline over the 6-month period.

Conclusions: both acute and chronic systemic inflammation, associated with increases in serum tumor necrosis factor alpha, is associated with an increase in cognitive decline in Alzheimer disease.

Full text not available from this repository.

More information

Published date: 2009
Organisations: Primary Care & Population Sciences

Identifiers

Local EPrints ID: 365833
URI: https://eprints.soton.ac.uk/id/eprint/365833
ISSN: 0028-3878
PURE UUID: 0188d3ad-c963-4eb3-af6e-f4ed3b2deb7d
ORCID for C. Holmes: ORCID iD orcid.org/0000-0003-1999-6912
ORCID for D.J. Culliford: ORCID iD orcid.org/0000-0003-1663-0253

Catalogue record

Date deposited: 17 Jun 2014 11:30
Last modified: 10 Dec 2019 01:50

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