An Italian study, coordinated by Humanitas Research Hospital and the Institute of Neuroscience of the CNR in Pisa, measured the effects of a program aimed at preventing neurodegenerative diseases. Physical and cognitive activity, in an enriched social context, increases anti-inflammatory molecules that protect the brain.

Combining physical exercise, cognitive stimulation, and nurturing social relationships can have a significant impact on the health of the aging brain. A recent Italian study published in the journal Brain, Behavior & Immunity – Health demonstrated that a multidimensional intervention called “Train the Brain” can improve cognitive functions in individuals with mild cognitive impairment (MCI) and modulate the inflammatory response of the immune system, with effects measurable through a blood test.

The research, led by Humanitas Research Hospitaland the Institute of Neuroscience of the National Research Council of Pisa (Cnr-In), in collaboration with the Institute of Clinical Physiology of the CNR (Cnr-Ifc), the Stella Maris Foundation, and the Neurology Clinic of AOUP, is part of a growing body of studies recognizing chronic inflammation as one of the main biological processes associated with aging and the development of neurodegenerative diseases such as Alzheimer’s disease, in a phenomenon known as inflammaging.

While all individuals experience a physiological decline in cognitive functions with age, there is a specific subgroup in which these changes are more pronounced and measurable: individuals diagnosed with MCI. These people not only show cognitive deterioration beyond what is expected for their age but also have a high risk of developing Alzheimer’s disease. For this reason, they are prime candidates for strategies aimed at preventing or delaying the progression of their condition.

Individuals with MCI often exhibit elevated levels of pro-inflammatory cytokines. These molecules, acting as key messengers of the immune system, can have deleterious effects when present in excess in the nervous system, compromising neuronal function, reducing synaptic plasticity, and promoting neurodegenerative mechanisms.

The research was funded by Fondazione Pisa and Fondazione Cariplo.

The “Train the Brain” program: a mind-body multidimensional intervention

To effectively counteract these processes, researchers at the Institute of Neuroscience of the CNR (IN-CNR) in Pisa developed the “Train the Brain” program, carried out at the Palestra della Mente within the CNR Research Area in Pisa, a facility entirely dedicated to studies aimed at counteracting brain aging. The program is based on an integrated, multidimensional approach to brain health, combining physical activity to promote vascular and metabolic health, cognitive stimulation exercises to maintain and enhance brain functions, and social interactions in a dedicated environment to counteract isolation and foster emotional well-being. The goal is to simultaneously act on multiple dimensions of aging to promote brain health in at-risk individuals.

“The first studies on the ‘Train the Brain’ program have shown very promising results in terms of improved cognitive abilities (particularly memory and attention functions) and structural brain changes detected via MRI, including improved cerebral blood perfusion and greater preservation of gray matter volume in cortical areas involved in executive functions,” says Prof. Alessandro Sale, Research Director and group leader at Cnr-In Pisa. “Furthermore,” Sale continues, “the beneficial effects of the training persist over time and do not appear to be influenced by factors such as gender, age, or education level, although improvement seems more pronounced in women and in individuals with lower educational attainment.”

However, the understanding of the mechanisms underlying these changes was still limited. To shed light on the molecular bases of the benefits of programs like “Train the Brain,” researchers at the Humanitas Research Hospital, led by Prof. Michela Matteoli, Director of the Humanitas Neuroscience Program, focused on the role of the immune system. The study involved 76 individuals diagnosed with MCI, divided into two groups: an experimental group, which participated in the 7-month multidimensional program, and a control group, which received only informational support. At the beginning and end of the intervention, participants underwent cognitive assessments, brain MRI scans, and blood analyses to quantify levels of pro- and anti-inflammatory cytokines.

“The results showed, in the ‘Train the Brain’ group, a significant reduction in plasma levels of molecules associated with systemic inflammation and cognitive decline, such as IL-6, IL-17A, TNF-α, and CCL11,” explains Michela Matteoli. “At the same time, we observed maintenance or increases in anti-inflammatory molecules known for their neuroprotective effects (IL-10, TGF-β, and IL-4). Among these, IL-10, which plays an important role in neuron survival and adult neurogenesis, increased after training and correlated with both short- and long-term memory performance, representing a potential marker for monitoring the effectiveness of motor and cognitive stimulation programs in at-risk individuals.”

Overall, the “Train the Brain” program has been shown to act not only on psychological and motivational levels but also on central biological processes crucial for maintaining brain health during aging.

Lifestyle helps keeping your brain young – and we can measure it

“The study reinforces a fundamental concept: the brain is strongly influenced by lifestyle,” concludes Genni Desiato, postdoctoral researcher at Humanitas Research Hospital. “Physical activity, cognitive stimulation, and social relationships exert a strong and direct impact on brain health and systemic inflammation, capable of acting in a measurable and profound way, down to the molecular level.”

Adopting an active lifestyle, regularly combining physical exercise and cognitive training, can slow or even reverse early signs of decline. And the good news is that it is never too late to start: even simple daily habits such as walking, stimulating the mind with reading or games, and maintaining an active social life can make a big difference. These practices are not just “good habits” but real, accessible preventive strategies for healthy aging.