HEALTH NEWS

Study Title:

Acute Inflammation, Infection, and the Rapid Progression of Alzheimers

Study Abstract

Background: Acute and chronic systemic inflammation are characterized by the systemic production of the proinflammatory cytokine tumor necrosis factor (TNF-) 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- 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- and a 2-fold increase in the rate of cognitive decline over a 6-month period. High baseline levels of TNF- were associated with a 4-fold increase in the rate of cognitive decline. Subjects who had low levels of serum TNF- 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 , is associated with an increase in cognitive decline in Alzheimer disease.

From press release:

Getting a cold, stomach bug or other infection may lead to increased memory loss in people with Alzheimer's disease, according to research published in the September 8, 2009, print issue of Neurology®, the medical journal of the American Academy of Neurology.

The study found that people who had respiratory, gastrointestinal or other infections or even bumps and bruises from a fall were more likely to have high blood levels of tumor necrosis factor-α, a protein involved in the inflammatory process, and were also more likely to experience memory loss or other types of cognitive decline than people who did not have infections and who had low levels of the protein.

The blood levels and cognitive abilities of 222 people with Alzheimer's disease with an average age of 83 were measured at the beginning of the study and three more times over six months. Caregivers were interviewed to determine whether the participants had experienced any infections or accidental injury that could lead to inflammation.

A total of 110 people experienced an infection or injury that led to inflammation during the study. Those people experienced memory loss that was at twice the rate of those who did not have infections or injuries.

People who had high levels of the protein in their blood at the beginning of the study, which may indicate chronic inflammation, had memory loss at four times the rate of those with low levels of the protein at the start of the study. Those who had high levels of the protein at the start of the study who also experienced acute infections during the study had memory loss at 10 times the rate of those who started with low levels and had no infections over the six-month period.

"One might guess that people with a more rapid rate of cognitive decline are more susceptible to infections or injury, but we found no evidence to suggest that people with more severe dementia were more likely to have infections or injuries at the beginning of the study," said study author Clive Holmes, MRCPsych, PhD, of the University of Southampton in the United Kingdom. "More research needs to be done to understand the role of tumor necrosis factor-alpha in the brain, but it's possible that finding a way to reduce those levels could be beneficial for people with Alzheimer's disease."

The study was supported by the Alzheimer's Society in London, UK.

Study Information

C. Holmes, MRCPsych, PhD, C. Cunningham, PhD, E. Zotova, BSc, J. Woolford, RMN, C. Dean, RMN, S. Kerr, RGN, D. Culliford, MSc and V. H. Perry, PhD
Systemic inflammation and disease progression in Alzheimer disease
NEUROLOGY
2009 September
Clinical Neurosciences Division and School of Biological Science, University of Southampton, UK