Plasma leptin, but not adiponectin, is associated with cognitive impairment in older adults

Leptin and adiponectin are adipose-tissue derived hormones primarily involved in glucose, lipid, and energy metabolism, inflammation, and atherosclerosis. Both adipokines may cross the blood-brain barrier but evidence on their roles in cognitive impairment is limited and conflicting. Here, we determined associations of plasma adipokine concentration with cognitive impairment in older adults.

Cross-sectional analysis of baseline data from 669 participants aged ≥65 years of the Biomarker Development for Postoperative Cognitive Impairment in the Elderly (BioCog) study were recruited 2014-2017 at study sites in Berlin, Germany and Utrecht, the Netherlands. Cognitive impairment was defined as the lowest tertile of a cognitive summary score derived from six neuropsychological tests.

After adjustment for age, sex, fasting, BMI, diabetes, hypertension, cerebrovascular disease, and coronary heart disease, higher leptin concentrations and a higher leptin/adiponectin ratio (LAR) were associated with a higher odds of cognitive impairment (OR per 1 SD higher leptin concentration, 1.33; 95 % CI 1.05, 1.69; p = 0.02; OR per 1 SD higher LAR, 1.26; 95 % CI 1.01, 1.57; p = 0.04). Sensitivity analyses determined that these findings were driven by the non-obese group (BMI < 30 kg/m²), whereas leptin and LAR were not associated with cognitive impairment in the obese group (BMI ≥ 30 kg/m²). Soluble leptin receptor, leptin/soluble leptin receptor ratio, total adiponectin and high-molecular weight adiponectin concentrations were each not associated with impairment.

With leptin as a known promoter of atherosclerosis and inflammation, our findings point to a pathogenic role of leptin in age-related cognitive impairment that may be limited to non-obese individuals and warrants further investigation.