Cited by 1,139Dementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatments

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Systemic inflammation and disease progression in Alzheimer disease

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Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., Perry, V. H.·2009·Neurology

DOI 10.1212/wnl.0b013e3181b6bb95PMC PMC2848584

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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.

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Authors: Holmes, C., Cunningham, C., Zotova, E., Woolford, J., Dean, C., Kerr, S., Culliford, D., & Perry, V. H.
Affiliations: Trinity College Dublin (IE)
ORCID: Holmes, C.
Cunningham, C.
Culliford, D.
Perry, V. H.
Venue: Neurology
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-09-08
Volume: 73
Issue: 10
Pages: 768-774
ISSN: 0028-3878 (ISSN-L)
1526-632X
DOI: 10.1212/wnl.0b013e3181b6bb95
PMC: PMC2848584
OpenAlex: W2085558085
Semantic Scholar: cbac9326b978c2365dec0a3f265816a795105bb1
Cited by: 1,139
References: 42
Citations by year: 2026: 48 · 2025: 68 · 2024: 85 · 2023: 75 · 2022: 77 · 2021: 87 · 2020: 84 · 2019: 89 · 2018: 71 · 2017: 71 · 2016: 59 · 2015: 67 · 2014: 57 · 2013: 55 · 2012: 58
FWCI: 29.59
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Neurology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
ePrints Soton (University of Southampton) (submittedVersion)
Funders: Wellcome Trust (078300)
National Institute for Health and Care Research
National Institutes of Health (5rc2ag036502-02)
Biotechnology and Biological Sciences Research Council
National Institute on Aging (R01AG012101)
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Keywords: Alzheimer's disease, systemic inflammation, TNF-α, cognitive decline, disease progression, neuroinflammation, microglial activation, inflammatory cytokines, serum biomarkers
MeSH terms: Acute Disease, Aged, Aged, 80 and over, Alzheimer Disease, Chronic Disease, Cognition Disorders, Female, Follow-Up Studies, Humans, Male, Prospective Studies, Retrospective Studies, Tumor Necrosis Factor-alpha, Cohort Studies, Biomarkers, Disease Progression, Inflammation Mediators

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Systemic inflammation and disease progression in Alzheimer disease

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