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Association Between Inflammatory Biomarkers and Cognitive Aging

Yuan Fang, Margaret F. Doyle, Jiachen Chen, Michael L. Alosco, Jesse Mez, Claudia L. Satizabal, Wei Qiao Qiu, Joanne M. Murabito, Kathryn L. Lunetta

Inflammatory cytokines and chemokines related to the innate and adaptive immune system have been linked to neuroinflammation in Alzheimer’s Disease, dementia, and cognitive disorders. We examined the association of 11 plasma proteins (CD14, CD163, CD5L, CD56, CD40L, CXCL16, SDF1, DPP4, SGP130, sRAGE, and MPO) related to immune and inflammatory responses with measures of cognitive function, brain MRI and dementia risk.

Systemic inflammation plays a key role in the disease pathology of Alzheimer’s Disease (AD) and related dementias. Existing literature has examined various inflammatory and cellular immunity biomarkers related to cognitive and brain aging. Chronic peripheral inflammation, as measured by C-reactive protein, is associated with an increased risk of dementia, including AD dementia, and MRI-derived biomarkers of brain atrophy among persons with increased genetic susceptibility to AD.


Study Sample
The FHS is a community-based prospective cohort study that recruited 5209 participants as the Original cohort in 1948. The Offspring cohort, recruited in 1971 (n = 5129), includes adult children who had at least one parent in the Original cohort and their spouses. Offspring participants have received examinations once every 4–8 years since enrollment. There were 3539 Offspring participants who attended the seventh examination (1998–2001), 3295 of whom provided a blood sample for quantifying the protein biomarkers of interest.

Inflammatory Protein Biomarkers
The Systems Approach to Biomarker Research in Cardiovascular Disease initiative measured 85 plasma proteins in the participants of the FHS Offspring cohorts. From these, we chose 11 protein biomarkers related to innate or adaptive immune cells or known to be associated with inflammatory responses for our investigation, as mounting evidence demonstrates a role for immune cells and inflammation in the disease pathogenesis of AD dementia and cognitive disorders.

Blood-based biomarkers for cognitive decline and dementia are of high interest due to their low cost and lack of need for invasive procedures. Therefore, this field of study is highly active. We observed several findings from our investigation of the association between 11 circulating inflammatory biomarkers with neuropsychological test performance, structural MRI-derived volumetric indices, and risk of incident dementia in a large community-based cohort of older adults.

The authors thank the Framingham Heart Study participants, as well as the study team for their contributions.

Citation: Fang Y, Doyle MF, Chen J, Alosco ML, Mez J, Satizabal CL, et al. (2022) Association between inflammatory biomarkers and cognitive aging. PLoS ONE 17(9): e0274350.

Editor: Muhammad Tarek Abdel Ghafar, Tanta University Faculty of Medicine, EGYPT

Received: June 17, 2022; Accepted: August 25, 2022; Published: September 9, 2022.

Copyright: © 2022 Fang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: The data that support the findings of this study are available from the Framingham Heart Study through NHLBI’s Biologic Specimen and Data Repository Information Coordinating Center (BioLINCC).

Funding: This work was supported by the National Heart, Lung, and Blood Institute and the Boston University School of Medicine, Framingham Heart Study (contract number 75N92019D00031); and by the National Institute on Aging (grant number R01AG067457 (awarded to MFD, JMM, and KLL), U19AG068753, P30AG072978 (awarded to MLA)); and National Institutes of Neurological Disorders and Stroke (grant number K23NS102399 (awarded to MLA)). The Neuropsychological testing data and brain MRI data were collected with funding from the National Institutes on Aging and Neurological Disorders and Stroke grants (grant number R01AG016495, R01AG008122, R01AG033040, R01AG054076, R01AG049607, R01AG033193, and R01NS017950).

Competing interests: The authors have declared that no competing interests exist.

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