The D’Or Institute for Research and Education (IDOR) in partnership with the Federal University of Rio de Janeiro, Oswaldo Cruz Foundation (Fiocruz), Federal University of Latin American Integration (UNILA) and Queen’s University of Canada, published a study in scientific journal The Journal of the Alzheimer’s Association that evaluated the role that hormone irisin and the lipoxin A4 molecule play in patients with depression. 

Depression has a high incidence in the elderly population and is a risk factor for dementia. Studies suggest that some biological factors may link both conditions, including brain inflammation, decreased volume of the hippocampus, which is a region of the brain involved with learning and memory, and deficits in brain-derived neurotrophic factor (BDNF, brain-derived neurotrophic factor) which is a protein related to the maintenance and survival of neurons. 

Doctor Fernanda de Felice, a researcher at IDOR and the Queen’s University, has been investigating the role of irisin for years, a hormone released during physical exercise that can reduce inflammation. In patients and animal models with Alzheimer, irisin levels are reduced both in the brain and in the cerebrospinal fluid (CSF) – a fluid present throughout the nervous system. This result suggests that the increase in irisin may help memory and the adaptability of neuronal synapses, protecting the brain from aging. This study led by De Felice was recognized in the Inge Grundke-Iqbal Award in Alzheimer’s Research – Alzheimer’s Association of the United States (USA), in 2021. Furthermore, the research group also demonstrated, in a previous study, that levels of irisin and BDNF correlate in the CSF. 

Lipoxin A4 is an anti-inflammatory molecule, that is, it acts in the resolution of inflammatory responses. Studies suggest when this molecule has reduced levels, the patient becomes unable to function in an inflammatory process and, therefore, may contribute to the development of Alzheimer’s. In addition, experiments with mice observed that when lipoxin A4 levels are restored, there is an improvement in the cognitive performance of these animals. 

Taking this information into account, the researchers analyzed the relationship between irisin, lipoxin A4, and BDNF in the CSF of elders without depression (control group) and those with depression who had or did not present cognitive impairment. The patients were diagnosed at the Memory Clinic, an IDOR service specialized in adult memory problems. For the study, CSF samples from 61 people were collected by lumbar puncture, and the levels of these three molecules were evaluated. 

The study observed that the levels of irisin, lipoxin A4 and BDNF were reduced in these samples. The reduction of these molecules suggests a mechanism shared between psychiatric disorders, such as depression and dementia, demonstrating evidence of new paths for study. 

The study authors report that prevention of abnormal brain inflammation in patients with depression and/or dementia requires stimulation of anti-inflammatory responses. Therefore, further evaluations of the effects of these molecules on the human body are needed. In addition, factors such as sleep quality, stressful life events, socioeconomic status, and diet are associated with the risk of depression, and may result in the variability of irisin, lipoxin A4, and BDNF levels observed in the study. Physical exercise can be a valuable tool for depression and dementia, alleviating symptoms and smoothing cognitive decline. A therapeutic proposal based on irisin may be important for elderly patients with severe depression and dementia and for people with mobility problems or other conditions related to aging since adherence to exercise is low in these patients. Randomized clinical trials are still needed to assess the safety, feasibility, and optimal dose for irisin treatment in humans.