Systemic 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.
Holmes
C
C
Clinical Neurosciences Division, University of Southampton, UK. ch4@soton.ac.uk
Cunningham
C
C
Zotova
E
E
Woolford
J
J
Dean
C
C
Kerr
S
S
Culliford
D
D
Perry
V H
VH
D000208:Acute Disease; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D003072:Cognition Disorders / Q000175:diagnosis / Q000276:immunology* / Q000473:pathology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood* / Q000502:physiology; D008297:Male; D011446:Prospective Studies; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood / Q000502:physiology*
D015415:Biomarkers; D018836:Inflammation Mediators; D014409:Tumor Necrosis Factor-alpha