Systemic inflammation and disease progression in Alzheimer disease.
Holmes C, Cunningham C, Zotova E, et al. Neurology. 2009;73(10):768-774.
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.
In recent years, there have been research studies with individuals without dementia that have investigated the role of low-grade systemic inflammation associated with cognitive decline. Some studies have also suggested that increased systemic inflammation may be associated with an increased risk of developing Alzheimer disease (AD). This well-designed research study’s conclusion that both acute and chronic systemic inflammation associated with increases in specific markers is associated with cognitive decline in AD has dental implications. This article generated a letter to the editor and a response from the primary author of this article. The letter from A.R. Kamer, a faculty member at New York University College of Dentistry, addressed that fact that systemic inflammatory markers evaluated for AD patients are associated with periodontopathic bacteria. The response to this letter by the authors was an agreement with Dr. Kamer that periodontitis probably plays an important role in disease progression of AD patients. This parallels the research path for the evaluation of causality of dental disease with systemic disease. Much more needs to be done before definite causality can be implemented, but it certainly is a start.
Commentary by Howard E. Strassler, DMD
Professor and Director of Operative Dentistry
Department of Endodontics, Prosthodontics and Operative Dentistry
University of Maryland Dental School