Low blood adropin flags poor learning and decision-making in aged rhesus monkeys

Finding blood-based markers that identify who is vulnerable to age-related cognitive decline is a major goal in aging research. Adropin is a peptide hormone first described as a liver-derived factor that coordinates glucose handling and mitochondrial function between fed and fasted states. It is also expressed in the brain, especially in astrocytes. In older adults, low circulating adropin has been associated with higher risk of cognitive decline, and rodent studies show that giving adropin can improve cognition and protect the blood-brain barrier. Whether the link holds in a primate with a more human-like brain was unclear.

This study used the aging rhesus macaque colony at the California National Primate Research Center. It pooled two cohorts of nondiabetic male and female animals: the Geriatric Behavioral Assessment (n = 118, mean age 17.3 years, tested in a sound-proofed suite) and the Geriatric Mobile Assessment (n = 57, mean age 19.1 years, tested in their home cages). Animals were offered food items in 2-, 3- and 4-choice tests (4 trials each) of increasing complexity, with up to 30 seconds to choose. The main measures were reaction time (RT) and its variability (RTSD). Plasma adropin was then related to these measures.

Reaction time fell stepwise across the tests (about 9.6 s, 8.2 s, then 4.4 s), and variability also fell, which indicates learning and familiarity with the task. Faster responding was modestly linked to more choices that contradicted earlier preferences (ρ around −0.32 to −0.34), so speed may come at some cost in accuracy. Animals with slow initial responses showed the steepest improvement. Housing and testing context mattered: outdoor-housed animals, who were moved to an unfamiliar suite, had longer latencies and improved later than indoor-housed animals. The two cohorts were therefore analyzed separately. According to the abstract, higher plasma adropin was associated with faster improvement in RT and reduced RT variability. Low adropin was associated with poorer decision-making, mainly when animals had to adapt to novelty or stress, while performance on simple tasks was preserved.

The authors interpret adropin as a marker of cognitive resilience rather than baseline executive capacity. This fits rodent evidence tying adropin signaling to mitochondrial function, resistance to oxidative stress and hippocampal-dependent learning. If confirmed, circulating adropin could serve as a conserved, translational biomarker for identifying people at risk of cognitive decline and as a possible therapeutic target.

The work is observational, so it cannot show that adropin affects cognition. Results depended heavily on environment and familiarity, and the full text available here was truncated before the adropin-specific statistics, so effect sizes cannot be reported.