A program based on the combination of physical activity and mental stimulation in a socially active environment is capable of increasing the production of molecules with anti-inflammatory functions that also exert a protective effect on brain tissue. A “gym” for the mind that seems able to help slow down cognitive decline and, in certain contexts, even reverse its degenerative trend.
“Train the Brain,” the name of the program developed through the collaboration between the IRCCS Istituto Clinico Humanitas in Rozzano and the Institute of Neuroscience of the National Research Council in Pisa, would have demonstrated positive effects on the patient’s psychological state and motivation and on biological processes crucial for maintaining brain health during aging, measurable with specific clinical and blood parameters. The study, published in Brain, Behavior & Immunity – Health, thus suggests the capacity of a multifactorial program to prevent neurodegenerative diseases, especially in the cluster of patients with Mild Cognitive Impairment (MCI).
The Evidence
At the center is chronic inflammation, scientifically regarded as one of the main biological mechanisms that drive the aging process, and thus some aging-related brain diseases like Alzheimer’s, sparked by the phenomenon known as inflammaging. Although cognitive decline is a physiological process to which everyone is exposed, there is evidence that in the population with MCI, these processes can occur more rapidly than in conditions of mental health.
The crucial point is that patients with MCI, in addition to showing greater cognitive decline than their chronological age would suggest, exhibit a markedly higher risk of developing Alzheimer’s. This population, therefore, represents the optimal target for measuring outcomes and the effectiveness of a program designed to inhibit or slow, alongside standardized pharmacological approaches, the evolution of MCI toward more severe conditions.
An added value of the program is its potential ability to regulate the inflammatory response of the immune system, with results measurable through specific blood tests.
The Study
So far, the program has been tested on small numbers: 76 patients with MCI aged between 65 and 80, divided into two groups: an experimental group, started on the multidimensional intervention lasting 7 months, and a control group that received only informational support. At the start and end of the study, participants underwent cognitive assessments, brain MRI, and blood analyses to quantify levels of pro- and anti-inflammatory cytokines, these molecules acting as key messengers of the immune system.
However, when present in excess in the nervous system, they can promote neuronal dysfunction, reduce synaptic plasticity, and thus foster neurodegenerative mechanisms. Proinflammatory cytokines are typically present at markedly increased levels in patients with MCI. The ideal target, therefore, for measuring the effects and efficacy of the Train the Brain program, which relies on three specific components, was not chosen at random:
- Physical activity, which helps optimize cardiovascular and metabolic health, with effects that become noticeable only when conducted consistently and regularly.
- Stimulation exercises, which help preserve and enhance cognitive functions, particularly memory and attention. These stimulation activities have been associated with structural brain changes detectable by MRI, including improved cerebral blood flow and greater preservation of gray matter volume in regions responsible for executive functions. Moreover, these benefits persist over time and are not significantly influenced by sex, age, or educational level, although the positive effect appeared more pronounced in women and in individuals with lower educational attainment.
- Social interaction, in a dedicated environment, helps combat isolation and promote emotional well-being.
The ultimate goal is to intervene synergistically on multiple fronts of aging to support neurological health in people at risk or diagnosed with MCI.
The Results
The data show the benefits of the “Train the Brain” program (TTB) compared with the control group. Specifically, MCI participants in the intervention group exhibited elevated baseline levels of IL-17A, CX3CL1, and CCL11, with a borderline increase in IL-6 and TNFα. After the TTB intervention, a reduction in plasma levels of molecules linked to systemic inflammation and cognitive decline (IL-6, IL-17A, TNFα, and CCL11) was observed. Regarding anti-inflammatory cytokines (IL-10, TGFβ, IL-4) and BDNF, these decreased in the control group and remained stable or increased in the intervention group.
In particular, IL-10, which plays a vital role in neuron survival and adult neurogenesis, was increased after training, showing a direct correlation with memory performance. Based on this finding, IL-10 is considered a potential biological marker to monitor the effectiveness of stimulation interventions. The TTB intervention proved capable of improving cognitive and physical outcomes and of modulating key immune markers associated with neuroinflammation and aging. IL-10, in particular, emerged as a potential peripheral biomarker of the training’s effectiveness. These results support the usefulness of the immune profile in monitoring responses to multi-domain interventions and guiding personalized strategies to reduce cognitive risk.
Source: Desiato G, Bosco P, Cintoli S et al. An inflammatory fingerprint in mild cognitively impaired patients is reversed by physical and cognitive training. Brain Behav Immun Health, 2025, 48:101062. DOI: 10.1016/j.bbih.2025.101062
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