Childhood dementia: synaptic hyperactivity as an early trigger in a brain in decline

By Elodie Vaz | Published on Avril 23, 2026 | 3 min read


Sanfilippo syndrome, a common form of childhood dementia, is a rare genetic disease characterized by progressive and fatal neurodegeneration. Affected children initially develop normally before rapidly losing cognitive abilities, language, and motor skills. Early clinical signs—hyperactivity, sleep disturbances, erratic behavior—precede an inexorable decline. In Australia, around 1,400 children are affected, and hundreds of thousands of cases are reported worldwide. Behind these numbers are deeply disrupted family lives. “It’s like grieving the life of your child before it has even begun,” said Tenille Koistinen, mother of an affected child, in a press release.

Deciphering early disease mechanisms

In the absence of curative treatment, understanding early cellular mechanisms is a major challenge. A study published on April 7 in Nature Communications, conducted by an international collaboration led from Australia, aims precisely to identify the initial alterations responsible for neurological decline. For Professor Cedric Bardy, lead researcher and director of the Neurophysiology and Human Genetics Laboratory at the South Australian Health and Medical Research Institute (SAHMRI) and Flinders University, the goal was to move beyond the view of a purely late-stage degeneration and instead explore dysfunctions occurring at the earliest stages of brain development.  

A stem cell–based experimental approach

To achieve their findings, researchers used cortical neurons derived from human stem cells obtained from patients with Sanfilippo syndrome. These cellular models were analyzed using advanced electrophysiological and molecular techniques, allowing detailed observation of synaptic activity and neuronal network organization. This in vitro approach made it possible to replicate stages of brain development and identify emerging abnormalities as neurons matured.

Overactive synapses from early development

The results reveal chronic hyperactivity in neuronal circuits. “What we observe in these children’s neurons is an increase in excitatory activity that disrupts the brain’s natural balance,” explained Professor Bardy in a press release. Initially functional, neurons gradually become hyperactive, generating bursts of intense and synchronized electrical activity. This dynamic mirrors the symptoms observed clinically.  

“This hyperactivity provides a clear biological explanation for early behavioral changes and brings us closer to understanding the complex mechanisms underlying childhood dementia.” Moreover, the study shows that these neurons are particularly vulnerable to metabolic stress. Even a mild nutritional deficiency worsens synaptic abnormalities, suggesting that environmental factors may accelerate disease progression.  

“Our research shows that disrupted synaptic communication is not merely a byproduct of degeneration—it is an early driver of the disease.” This shift in perspective positions synapses as primary therapeutic targets.

Toward personalized medicine for childhood dementia

These findings open major new avenues. “This research is important not only for Sanfilippo syndrome but for the field of childhood dementia as a whole,” said Megan Maack, CEO and founder of the Childhood Dementia Initiative. By identifying precise cellular mechanisms, researchers are now considering personalized medicine approaches.  

Preclinical studies have already shown that certain existing drugs can correct these synaptic imbalances. “Encouragingly, we have already demonstrated in the lab that these synaptic imbalances can be corrected,” noted Professor Bardy, pointing to a tangible therapeutic target. The team now has “a new preclinical tool” to evaluate such treatments.  


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About the Author – Elodie Vaz
Health journalist, CFPJ graduate (2023).
Élodie explores the marks diseases leave on bodies and, more broadly, on human life. A registered nurse since 2010, she spent twelve years at patients’ bedsides before exchanging her stethoscope for a notebook. She now investigates the links between environment and health, convinced that the vitality of life cannot be reduced to that of humans alone.