A team from the Institute of Neurosciences of the University of Barcelona (UBneuro) has discovered that early and sustained cognitive stimulation can help preserve brain connectivity and memory in Alzheimer’s disease, even in advanced stages of the pathology. The study, published in the journal
iScience and carried out with animal models, also reveals that males respond better than females to cognitive intervention to delay the onset of the disease.
Cognitive stimulation as a protective strategy
Alzheimer’s disease, the leading cause of dementia worldwide, is characterized by a progressive and irreversible deterioration of cognitive function. Given the lack of effective curative treatments, strategies that delay its onset or slow its progression are increasingly considered a key way to reduce its clinical and social impact. In this context, cognitive reserve — the brain’s ability to maintain functions despite the underlying pathology — has become one of the most studied protective factors.
In the study, the team analyzed whether long-term cognitive stimulation, initiated before the appearance of amyloid pathology typical of Alzheimer’s, could improve brain resilience in an animal model of the disease.
Therefore, the animals underwent repeated cognitive training throughout their lives. Brain function was assessed using longitudinal resting-state functional magnetic resonance imaging, behavioural memory tests, and comprehensive molecular and cellular analyses.
“The cognitively trained animals preserved memory (especially the males) and functional connectivity between key brain regions involved in memory, in particular the entorhinal cortex and the hippocampus, which are especially vulnerable in Alzheimer’s disease,” says Professor Guadalupe Soria, from the Faculty of Medicine and Health Sciences and UBneuro, who led the study.
“Furthermore, the preservation of brain connectivity was associated with better memory performance at older ages. This reinforces the idea that cognitive engagement in the early stages of life can have lasting protective effects on brain function,” the researcher points out.
Different results between males and females
The study highlights that the benefits of cognitive stimulation were not the same in males and females. Females showed higher baseline levels of proteins related to synaptic function and plasticity, suggesting greater intrinsic molecular resilience. In contrast, male rats benefited more clearly from cognitive training, with sustained brain connectivity, improved memory performance, and restoration of markers of synaptic plasticity.
The results reinforce the growing evidence in preclinical and clinical research: Alzheimer’s disease progresses differently in men and women. Therefore, preventive and therapeutic strategies should be adapted to address this neurodegenerative pathology.
Brain networks, plasticity and neuroinflammation
Beyond the behavioural results, the study provides multiscale mechanistic information on how cognitive stimulation exerts protective effects. Trained animals showed a recovery of markers of synaptic plasticity, a modulation of inhibitory neuronal circuits, and a transient normalization of the microglial response around amyloid plaques. These results suggest the existence of a less reactive neuroinflammatory profile during middle age, a condition that may delay the cascade of pathological events.
Through brain imaging, behavioural studies and molecular biology, “this work establishes a direct link between the preserved organization of the brain network and cellular mechanisms of resilience, and thus reinforces the value of cognitive stimulation as a non-pharmacological strategy to promote brain health,” concludes Guadalupe Soria.