Systemic Inflammation Mediates Age-Related Cognitive Deficits

Abstract

The association between systemic inflammation and cognitive deficits is well-documented. Further, previous studies have shown that systemic inflammation levels increase with age. The present study took a novel approach by examining the extent to which systemic inflammation levels mediated age-related cognitive decline. Forty-seven young and 46 older generally healthy adults completed two cognitive tasks measuring processing speed and short-term memory, respectively. Serum concentrations of three inflammatory biomarkers (including interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), C-reactive protein (CRP)) were measured in each participant. Both cognitive measures showed age-related deficits. In addition, levels of IL-6 and TNF-α were elevated with age. IL-6 partially mediated the difference in processing speed between the young and the older participant age group; there was no mediation effect for TNF-α and CRP. Considering chronological age, IL-6 partially accounted for age-related impairment in processing speed within older but not young participants. No effects were found for short-term memory. Evidence from this research supports the role of inflammatory processes in age-related cognitive decline. Processes involved in this mediation and differences in inflammatory influence on specific cognitive functions are discussed.

Cognition Is Associated With Peripheral Immune Molecules in Healthy Older Adults: A Cross-Sectional Study

“…CRP, an acute phase protein, is vastly studied in geriatric populations and has been associated with an increased risk for cerebrovascular disease, Alzheimer’s disease, and vascular dementia ( 42 ). Some studies described no association between levels of CRP and cognitive performance in healthy senior individuals ( 6 , 40 , 43 ) as we do here, while others demonstrate an association between higher levels of CRP and worst cognitive performance ( 31 , 36 , 44 , 45 ). Interestingly, in those studies the CRP range is lower than in this study, indicating that other factors that vary between cohorts may mediate or dilute its impact on cognition.…”

The immune system on the TRAIL of Alzheimer’s disease

“…A low-grade peripheral immune/inflammatory response and the basal release of cytokines are needed to maintain brain homeostasis and functional plasticity, including hippocampal-dependent cognitive functions and neurogenesis, suggesting that the systemic immune response exerts a healing role in the CNS [6,7]. Now, it is a common notion that systemic inflammatory disorders may be associated with cognitive decline [8], and, in fact, chronic inflammation is known to inhibit neuronal functions and contribute to onset and progression of AD [9]. In this line, robust data support the crucial relevance of mediators of the inflammatory/ immune response in neurodegeneration, as, for instance, injured neurons release arrays of these molecules, which redundantly sustain neuronal damage and death [10].…”

Reply

“…3 Systemic inflammation and deficits in cognitive function are well documented. 4 We do acknowledge that plaque removal, in this instance, may also ameliorate the inflammation. However, there may be less invasive treatments that could remediate these altered biologic processes.…”

“…3 In contrast, others support that BMT alone may not be adequate for all patients with ACAS and that certain high-risk patient subgroups should be considered for a prophylactic CEA. 4 The two recent studies 1,2 suggest that besides reducing the risk of future stroke, another parameter that should be considered when debating on the optimal management of patients with ACAS is cognitive dysfunction. There is evidence that by correcting the carotid stenosis, CEA increases cerebral perfusion and improves cognitive function.…”

“…In 2019, 59 U.S. and 52 non-U.S. graduates, including foreign-trained U.S. graduates, applied to the 0 þ 5 pathway. 4 The 55 programs represented 66 spots, of which 6 were filled by international graduates, growing from 4 in 2015-2016.…”