Seizures Precede The Onset Of Frontotemporal Dementia In Many Cases

A new study has shown that people with frontotemporal dementia (FTD) are more likely to develop epilepsy than healthy people or people with Alzheimer's. Seizures can occur years before dementia is diagnosed and serve as an early warning sign of the disease. This could help doctors identify and treat FTD earlier, improving patient care.

Frontotemporal dementia (FTD) is a type of neurodegenerative disease that primarily affects the areas of the brain responsible for behavior, personality, and language. It is one of the most common forms of dementia in younger people, but it can also affect older people.

The condition can have a variety of manifestations, including changes in behavior, difficulty communicating, and even motor problems. In some cases, it is linked to genetic changes, such as a mutation in the gene called C9orf72, which is especially common in families with a history of the disease, especially in Scandinavia and Finland.

On the other hand, epilepsy is a condition characterized by seizures, which are abnormal electrical discharges in the brain. It is already known that people with diseases such as Alzheimer's have a higher risk of developing epilepsy, but little was known about this association in the case of frontotemporal dementia.

A recent study conducted in Finland sought to better understand this relationship between epilepsy and frontotemporal dementia. The researchers analyzed data from 245 patients diagnosed with frontotemporal dementia and compared them with more than 2,400 healthy people and 1,300 patients with Alzheimer's.

The goal was to see if epilepsy was more common among patients with frontotemporal dementia.

The results showed that it was: people with frontotemporal dementia had a higher rate of epilepsy both before and after the diagnosis of dementia. For example, 10 years before the diagnosis of frontotemporal dementia, 3.3% of these patients already had epilepsy, while this rate was only 0.8% in healthy people and 1.4% in those with Alzheimer's.

After diagnosis, the number increased even more: 11.2% of patients with frontotemporal dementia developed epilepsy within five years, a much higher percentage than in the other groups.

Prevalence of epilepsy among study groups at different time points.

In addition, the researchers found that patients with frontotemporal dementia purchased more anticonvulsant medications compared to the other groups, which reinforces the link between the two conditions.

The study suggests that in many cases, epilepsy may be one of the first signs that the brain is beginning to suffer the effects of frontotemporal dementia, appearing years before other, more well-known symptoms of dementia.

Prevalence of Anticonvulsant Medication Purchase Before Diagnosis of Frontotemporal Dementia. AD indicates Alzheimer's disease; HC, healthy control; FTD, frontotemporal dementia.

This finding is important because it may help clinicians suspect the presence of frontotemporal dementia earlier when an older patient presents with unexplained seizures.

This information helps to better understand how epilepsy and frontotemporal dementia may be linked, which opens the way for faster diagnosis and more appropriate treatments.

It also reinforces the need for further studies to understand how the two diseases are related and whether there are common mechanisms in their development, which in the future may lead to new treatments for both conditions.

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Prevalence of Epilepsy in Frontotemporal Dementia and Timing of Dementia Diagnosis

Annemari Kilpeläinen, Mikko Aaltonen, Kalle Aho, Sami Heikkinen, 

Ave Kivisild, Adolfina Lehtonen, Laura Leppänen, Iina Rinnankoski, Helmi Soppela, Laura Tervonen, Päivi Hartikainen, Annakaisa Haapasal, Reetta Kälviäine,Kasper Katisko, Johanna Krüger, and Eino Solje

JAMA Neurol, June 2, 2025. 

doi:10.1001/jamaneurol.2025.1358

Abstract:

Previous studies have described a potential association between epilepsy and frontotemporal dementia (FTD), but no systematic data are available.

Objective  To determine whether epilepsy is more prevalent in patients with FTD than in healthy controls (HCs) or patients with Alzheimer disease (AD). In this case-control study, we compared the prevalence of epilepsy and purchases of antiseizure medicines (ASMs) among patients with FTD, matched HCs, and patients with AD from 2 early-onset dementia diagnostics centers in the same geographic regions of Finland. AD or FTD diagnoses were made between January 1, 2010, and December 31, 2021. Data were analyzed from January 26, 2024, to January 16, 2025. The primary outcome was to describe the prevalence of epilepsy in patients with FTD, covering the time period from 10 years before to 5 years after the FTD diagnosis. We used International Statistical Classification of Diseases, Tenth Revision codes to identify all patients with epilepsy and tracked purchases of ASMs. The study cohort included 245 patients with FTD (121 female [49.4%], 124 male [50.6%]; mean [SD] age, 65.2 [8.7] years), 2416 matched HCs (1190 female [49.3%], 1226 male [50.7%]; mean [SD] age, 65.0 [8.5] years), and 1326 patients with AD (777 female [58.6%], 549 male [41.4%]; mean [SD] age, 71.7 [9.8] years). The prevalence of epilepsy was higher in the FTD group compared with the HC group (3.3% vs 0.8%, respectively; P = .002) and AD group (3.3% vs 1.4%, respectively; P = .01) 10 years before FTD diagnosis. At the year of the diagnosis, the prevalence was 6.5% in patients with FTD, 1.8% in HCs (FTD vs HC difference, 4.7 percentage points [ppt] [95% CI, 2.2-8.6 ppt]; P < .001), and 5.0% in patients with AD (FTD vs AD difference, 1.6 ppt [95% CI, −1.2 to 5.5 ppt]; P = .32); at 5 years after the diagnosis, the prevalence was 11.2% in patients with FTD, 2.2% in HCs (FTD vs HC difference, 9.0 ppt [95% CI, 5.0-14.6 ppt]; P < .001), and 6.9% in patients with AD (FTD vs AD difference, 4.2 ppt [95% CI, 0-10.0 ppt]; P = .05). ASM purchases were made significantly more often among patients with FTD (10.2%) compared with HCs (1.8%) and patients with AD (4.2%) (FTD vs HC difference, 8.4 ppt [95% CI, 5.2-12.9 ppt]; P < .001; FTD vs AD difference, 6.1 ppt [95% CI, 2.6-10.6 ppt]; P < .001) at all time points and increased during the study period. This case-control study found a higher prevalence of epilepsy and increased ASM use among patients with FTD compared with HCs and patients with AD , suggesting an association between epileptic abnormalities and the pathophysiology of FTD. Further studies are warranted to investigate a potential overlap in the pathophysiologic mechanisms of epilepsy and FTD.