Epileptic seizures are more common in patients with frontotemporal dementia (FTD) than previously known, according to a recent study. This discovery sheds new light on the symptoms of this memory disorder and emphasizes the importance of considering epileptic seizures in treatment and monitoring patients.

The research project, led by Neurocenter Finland, analyzed data from 12,490 medical records at the University Hospitals of Kuopio and Oulu between 2010-2021. The study identified 245 patients with FTD and found that epilepsy was significantly more common among them than those with Alzheimer’s disease or healthy controls.

“Our results show that epilepsy is considerably more common among those with FTD than those with Alzheimer’s disease or in healthy controls,” says Doctoral Researcher Annemari Kilpeläinen, the first author of the research article and a medical specialist in neurology. “It is noteworthy that epilepsy occurred in some patients with FTD already ten years before their dementia diagnosis, and it was more common in all the examined stages of the disease than previous international studies have reported.”

The prevalence of epilepsy increased over time in patients with FTD, reaching approximately 11% five years after the diagnosis. In addition to diagnosing epilepsy, medications used for epilepsy were more common among patients with FTD, further strengthening the reliability of the results.

Diagnosing epilepsy in patients with FTD can be challenging due to the resemblance between the symptoms of the disease and epileptic seizures. However, untreated epilepsy can significantly worsen patients’ condition. Identifying epilepsy is essential because its treatment can improve patients’ functional capacity and quality of life.

“Knowledge about the association between epilepsy and FTD raises new research questions: do these diseases share some pathophysiological mechanisms and could some FTD symptoms be caused by alterations in the specific electrical systems of the brain?” asks Associate Professor Eino Solje, the principal investigator of the project.

The recently published study is part of an extensive project that combines real-life patient data with different kinds of unique registers. The project involves a strong cooperation between the University of Oulu and the University of Eastern Finland as well as different fields of science, including between researchers in medicine and law.

Research has discovered that men who carry a common genetic variant are twice as likely to develop dementia in their lifetime compared to women. This groundbreaking study, published in Neurology, used data from the ASPirin in Reducing Events in the Elderly (ASPREE) trial to investigate whether people with variants in the haemochromatosis (HFE) gene might be at increased risk of dementia.

One in three people carry one copy of the H63D variant, while one in 36 carry two copies. Having just one copy of this gene variant does not impact someone’s health or increase their risk of dementia. However, having two copies of the variant more than doubled the risk of dementia in men, but not women.

The researchers emphasize that the genetic variant itself cannot be changed, but the brain pathways affected by it could potentially be treated if we understood more about it. Further research is needed to investigate why this genetic variant increased the risk of dementia for males but not females.

The findings suggest that perhaps testing for the HFE gene could be offered to men more broadly, considering its routine testing in most Western countries, including Australia, when assessing people for haemochromatosis – a disorder that causes the body to absorb too much iron. The study found no direct link between iron levels in the blood and increased dementia risk in affected men.

This points to other mechanisms at play, possibly involving the increased risk of brain injury from inflammation and cell damage in the body. Understanding why men with the double H63D variant are at higher risk could pave the way for more personalized approaches to prevention and treatment.

The ASPREE trial was a groundbreaking study that created a treasure trove of healthy ageing data, which has underpinned a wealth of research studies. This collaboration between Curtin University, Monash University, The University of Melbourne, The Royal Children’s Hospital, Murdoch Children’s Research Institute, and Fiona Stanley Hospital demonstrates the importance of diverse Australian research groups working together to improve health outcomes for people around the world.

The implications of this study are significant, considering that more than 400,000 Australians are currently living with dementia, with around a third of those being men. This discovery could lead to improved outcomes for people at risk of developing dementia and ultimately contribute to a better understanding of these progressive diseases.

The Broad Institute has made a groundbreaking discovery in treating Huntington’s disease and Friedreich’s ataxia by developing a novel approach to edit the genetic sequences responsible for these conditions. These severe neurological disorders are caused by repeated three-letter stretches of DNA that grow uncontrollably, leading to brain cell death or nerve fiber breakdown. The researchers have successfully disrupted this repeat sequence using base editing, a technique that introduces single-letter changes into the middle of the repeated stretch of DNA.

The study, published in Nature Genetics, was led by David Liu, the Richard Merkin Professor and director of the Merkin Institute of Transformative Technologies in Healthcare at the Broad. The research team included postdoctoral researcher Mandana Arbab, graduate student Zaneta Matuszek, and associate scientist Ricardo Mouro Pinto.

The breakthrough comes from the realization that some individuals with the same disease can inherit different numbers of DNA repeats, with more repeats generally leading to faster symptom progression. However, patients who have naturally occurring single-letter interruptions within these repeats often experience milder symptoms and are less likely to pass their disease along to their children. This observation inspired the researchers to develop a gene-editing therapy that could install an interruption mimicking those that occur naturally.

Using base editing, developed by Liu’s lab in 2016 for making single-letter changes in DNA, the team introduced interruptions into the repeat sequences of patient cells and mouse models of Huntington’s disease and Friedreich’s ataxia. The results showed that the edited DNA tracts stayed the same or even became shorter over time.

The researchers caution that more work is needed to catalog potential side effects of installing these edits in the genome, but the approach could be a valuable tool for understanding diseases caused by repeated three-letter sequences. “A lot more studies would be needed before we can know if disrupting these repeats with a base editor could be a viable therapeutic strategy to treat patients,” said Liu.

The team’s findings suggest that this gene-editing therapy could help treat Huntington’s, Friedreich’s ataxia, and other trinucleotide repeat disorders. “Not only does this study show for the first time that inducing interruptions has a profound stabilizing effect on repeats, but that the base-editing approach we’ve used can also be applied to study any of over a dozen repeat disorders,” said Arbab.

The research was supported by various organizations, including the Chan Zuckerberg Initiative, Lodish Family Foundation, National Institutes of Health, and Howard Hughes Medical Institute. The team is now developing a different approach using prime editing to replace disease-causing repeat tracts with a shorter, stable number of repeats all at once.