Summary: Brain folds formed during late fetal development may influence the age when symptoms of frontotemporal dementia appear.
Source: Lund University
Frontotemporal dementia typically begins earlier than many other dementias. While its causes remain incompletely understood, new research from Lund University indicates that cortical folding patterns established before birth may affect the age at which this disease manifests.
Frontotemporal dementia often strikes people at a relatively young age, frequently during their working years. The condition progresses quickly, and the average survival time after diagnosis is around eight years.
“There is currently no cure and no treatment proven to slow progression. That makes any additional insight into the disease particularly important,” says Alexander Santillo, Associate Professor of Psychiatry at Lund University and consultant psychiatrist.
In a magnetic resonance imaging (MRI) study of 307 participants aged 27–87, researchers compared three groups: 105 people diagnosed with frontotemporal dementia (also called behavioral variant frontotemporal dementia or bvFTD), 92 people with Alzheimer’s disease, and 110 healthy control participants. The study examined structural brain differences and their relationship to clinical outcomes.
The team focused on a specific anatomical feature called the paracingulate sulcus, a tertiary cortical fold that develops during the third trimester of pregnancy and is adjacent to the anterior cingulate gyrus. They found that the presence of an extra fold in the right hemisphere was associated with a later age at onset of frontotemporal dementia symptoms.
“Participants who had an additional paracingulate fold on the right side developed symptoms of frontotemporal dementia on average about three years later than those without that fold,” explains Luke Harper, neurology resident, doctoral student at Lund University and first author of the study. This association was specific to frontotemporal dementia and was not observed in the Alzheimer’s disease group.
The findings link prenatal brain morphology to the timing of a neurodegenerative disease many decades later. Genetic influences on dementia risk were already known, but this study highlights how early brain development may also shape disease expression.
“The fetal period is a time when the brain is especially sensitive to environmental and developmental factors,” says Alexander Santillo. “Until recently it was difficult to connect features of fetal neurodevelopment with conditions that emerge 60–70 years after birth. These results suggest that developmental variation can contribute to brain reserve and influence when symptoms appear.”
Why the observed effect appears to be lateralized to the right hemisphere is not yet fully understood. Frontotemporal dementia is known to affect the anterior cingulate and paracingulate regions of the cerebral cortex and is often associated with behavioral changes that implicate right-hemisphere networks. The study’s results suggest that anatomical variation in this specific region may modulate vulnerability or resilience to neurodegeneration.
The researchers note that while a minority of frontotemporal dementia cases are linked to known genetic mutations, the majority have unknown causes. Identifying developmental features that influence age at onset and potentially disease progression could help refine risk assessment and inform the design of future treatments.
“Our results indicate that variations in cortical folding should be considered when developing and testing new therapies,” Santillo adds. He emphasizes, however, that these findings require replication in other cohorts before clinical implications can be confirmed.
To validate and extend their results, Luke Harper has started collaborative follow-up studies with research teams in the United States and the Netherlands. Those projects aim to determine whether folding patterns in the paracingulate region not only affect age at onset but also influence disease progression and survival after diagnosis.
About this neurodevelopment research news
Author: Lotte Billing
Source: Lund University
Contact: Lotte Billing – Lund University
Image: The image is in the public domain
Original Research: Open access. “Prenatal Gyrification Pattern Affects Age at Onset in Frontotemporal Dementia” by Luke Harper et al. Published in Cerebral Cortex.
Abstract
Prenatal Gyrification Pattern Affects Age at Onset in Frontotemporal Dementia
The paracingulate sulcus is a tertiary sulcus formed during the third trimester. In healthy individuals paracingulate sulcation is more prevalent in the left hemisphere. The anterior cingulate and paracingulate gyri are focal points of neurodegeneration in behavioral variant frontotemporal dementia (bvFTD).
This study aimed to determine the prevalence and clinical impact of paracingulate sulcation in bvFTD. Structural magnetic resonance images were evaluated for hemispheric paracingulate sulcal presence in individuals with bvFTD (n = 105, mean age 66.9 years), Alzheimer’s disease (n = 92, mean age 73.3 years), and healthy controls (n = 110, mean age 62.4 years).
No difference in left-hemisphere paracingulate sulcal frequency was found between groups: 0.72, 0.79, and 0.70 in the bvFTD, Alzheimer’s disease, and healthy control groups, respectively (P = 0.3). A significant association was observed between right-hemisphere paracingulate sulcation and age at onset in bvFTD: mean age at onset was 60.4 years where the right sulcus was absent versus 63.8 years where it was present (P = 0.04, Cohen’s d = 0.42). This relationship was not seen in the Alzheimer’s disease group.
These findings demonstrate a relationship between prenatal neuronal development and the expression of a neurodegenerative disease, offering a morphological example of brain reserve that may influence when symptoms emerge.