Biomarkers.

Background: It is unclear whether inflammation, i.e., high interleukin-6 (IL-6) levels, and genetic risk, i.e., APOE ε4 allele, have a compounding effect on cognitive decline (CD).

Method: We analyzed a subset of participants from the longitudinal cohort study, Chicago Health and Aging Project, comprising 1,120 biracial community-dwelling older adults (60% African American & 62% women), and mean follow-up=6.4 years. We ran adjusted mixed-effects models of longitudinal cognitive decline and explored potential racial differences.

Result: In ε4 carriers, higher serum IL-6 was not associated with the rate of CD (β=-0.0091 (SD=0.0165, p=0.5800). Conversely, in non-ε4 carriers, compared to the lower tertile, those with the upper tertile of serum IL-6 levels experienced significantly accelerated CD [β=-0.0257 (SD=0.0084 p=,0.0023)]. These results did not differ between races.

Conclusion: Even without the largest genetic risk factor for late-onset AD/ADRD, elevated serum IL-6 still accelerate the rate of CD. Hence, interventions ameliorating inflammation may prevent AD/ADRD. In contrast to the ε4 allele, as serum IL-6 is a modifiable risk factor, these findings could implicate precision medicine, including AD/ADRD preventions and therapies to prevent AD/ADRD.