Aline Thomas1, Danurys Sanchez1, Dolly Reyes-Dumeyer2, Richard Mayeux3, Yian Gu3
1Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, 2Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and G.H. Sergievsky Center, 3Taub Institute for Research on Alzheimer’s Disease and the Aging Brain, and G.H. Sergievsky Center, Departments of Neurology and of Epidemiology, Columbia University, Columbia University
Objective:
To determine if circulating markers of inflammation are associated with cognitive decline in older adults.
Background:
Inflammation has been shown to play a major role in the development of dementia and cognitive aging in general. Studies have focused on major biomarkers of inflammation such as C-Reactive Protein (CRP), Interleukin-6 (IL-6) or Tumor Necrosis Factor-a (TNF-a). In the present study, we explored inflammatory profiles as the combination of 23 cytokine biomarkers, and their associations with cognitive decline.
Design/Methods:
We included 1,483 non-demented participants (≥65 years-old) from the 2009 cohort of Washington Heights-Inwood Community Aging Project (WHICAP). Inflammatory profiles were identified from Principal Component Analysis (PCA) on 23 blood cytokines biomarkers. Repeated cognitive assessments, performed every 18 to 24 months for up to 12.5 years, were used to assess cognitive decline in 4 cognitive domains (memory, language, executive speed, and visuospatial functions) and in global cognition.
Results:
The second PCA component identified an inflammatory profile characterized by negative loadings for anti-inflammatory cytokines (e.g., IL-3, IL-4, IL-10) and positive loadings for pro-inflammatory cytokines, such as MIP-1β and TNF-a. A higher score of this component, indicating more pro-inflammatory profile, and higher levels of its key drivers (MIP-1β and TNF-a) were associated with lower baseline cognitive performances for global cognition and executive speed, after adjustment for age, sex, race/ethnicity and ApoE-ε4. No association of PCA components with cognitive decline was observed in longitudinal analysis. However, VEGF and CRP were associated with a faster decline in global cognition. Additional adjustments on vascular risk factors only slightly attenuated the association.
Conclusions:
Among older adults, a pro-inflammatory immune profile is associated with lower baseline cognitive performances, and some individual pro-inflammatory cytokines might be associated with faster cognitive decline.