UCSF

Objectives

To determine the association between interleukin-6 (IL-6), IL-6 soluble receptor (sR), and soluble tumor necrosis factor receptor-1 (sTNF-R1) and cognitive status in the oldest-old women.

Design

Twenty-year longitudinal cohort study.

Setting

Four clinical sites in the United States.

Participants

Women from the Study of Osteoporotic Fractures (N = 905; mean age 88.3 ± 2.8 at cognitive status adjudication).

Measurements

At Year 20, cognitive status was adjudicated as normal, mild cognitive impairment (MCI), or dementia. Inflammatory markers were measured from blood serum at Years 10 and 16 in a random sample of women.

Results

Over 10 years, 199 (22.0%) women developed MCI and 145 (16.0%) dementia. There were no significant associations between IL-6 or sTNF-R1 and cognitive status. High IL-6-sR (≥ 37,401.36 pg/mL, highest tertile) at Year 16 was significantly associated with lower risk of dementia (odds ratio (OR) = 0.54, 95% confidence interval (CI) = 0.30-0.97) than in women with lower levels (<37,401.36 pg/mL, lower two tertiles). Women with high IL-6-sR at both time points (OR = 0.39, 95% CI = 0.17-0.89) or who transitioned to a high level (OR = 0.35, 95% CI = 0.14-0.88) had a lower risk of dementia.

Conclusion

In this cohort of white, high-functioning oldest-old women, a consistently high or an increasing level of IL-6-sR was associated with lower risk of dementia. Compared with other studies of younger-old adults, this suggests that the effect of inflammation on dementia may differ in younger-old and the oldest-old individuals. Understanding these differences will be crucial in interpreting results from ongoing clinical trials and in targeting therapeutic strategies to the oldest-old individuals.