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ABSTRACT & COMMENTARY
Epilepsy in Frontotemporal Dementia
July 1, 2025 3 minutes read
By Robert McInnis, MD
Synopsis: This Finnish case-control study explores the relationship between frontotemporal dementia (FTD) and epilepsy, revealing that individuals with FTD have a higher prevalence of epilepsy compared to those with Alzheimer’s disease (AD) and healthy controls. The findings suggest that epilepsy may precede FTD diagnosis and is more common in FTD than previously recognized, highlighting the need for broader research and clinical awareness of this comorbidity.
Source: Kilpelӓinen A, Aaltonen M, Aho K, et al. Prevalence of epilepsy in frontotemporal dementia and timing of dementia diagnosis. JAMA Neurol. 2025; Jun 2. doi: 10.1001/jamaneurol.2025.1358. [Online ahead of print].
Frontotemporal dementia (FTD) is the most common neurodegenerative condition to occur in younger populations and contributes substantially to disability in those affected. Epilepsy is a well-recognized comorbidity of Alzheimer’s disease (AD) and has been the focus of widespread research. Comparatively little is known about whether epilepsy is associated with FTD, with existing studies limited to small cohorts and with conflicting findings.
To address this knowledge gap, Kilpelӓinen and colleagues performed a case-control study examining patients with FTD, AD, and healthy controls (HC) and comparing the prevalence of epilepsy diagnoses and purchase of anti-seizure medications (ASMs). The study was executed as part of a Finnish clinical trial. Data were collected from patients residing in one of two provinces in Finland between 2010 and 2021, where all patients with a diagnosis of a neurodegenerative disease prior to age 65 years are referred to local university hospitals.
For each enrolled patient with neurodegenerative disease, 10 HC were selected at random and matched based on demographic characteristics and geographic location. Patients’ clinical trial data then were linked with nationally available data detailing ASM purchases, and the prevalence of epilepsy in the cohort was calculated using ICD-10 codes. The group with a neurodegenerative diagnosis was separated into FTD and AD, and comparisons were made between these two groups and to matched HC with respect to epilepsy prevalence and purchase of ASMs.
The most common genetic cause for FTD is a hexanucleotide repeat expansion in chromosome 9 gene C9orf72. This expansion is found in approximately 25% of familial cases of FTD and is prevalent in Scandinavia, where this study was performed.
The study cohort included 245 patients with FTD, with a mean age of 65.2 years; 2,416 HC with a mean age of 65.0 years; and 1,326 patients with AD, with a mean age of 71.7 years. Receipt of an ICD-10 diagnosis was used as a marker of an epilepsy diagnosis. The prevalence of epilepsy was examined in the population at four separate time points: 10 and five years prior to FTD diagnosis, the year of FTD diagnosis, and five years after diagnosis. Patients with FTD were found to have a higher rate of epilepsy in the preclinical period before FTD diagnosis compared to both HC and AD patients.
Over time, the rates of epilepsy diagnosis increased in a linear fashion in both FTD and AD, but with a greater mean rate in FTD than in AD at each of the examined time points: 3.3% vs. 1.4% 10 years prior to diagnosis, 4.9% vs. 1.7% five years prior to diagnosis, 6.5% vs. 5.0% at the year of diagnosis, and 11.2% vs. 6.9% five years after diagnosis. The rate of ASM purchasing followed the trend in diagnosis over time, with FTD ASM purchases greater than those for AD and HC over time. ICD-10 codes in FTD patients predominantly were for focal epilepsy syndromes.
Commentary
This case-control study offers compelling evidence of an association between FTD and epilepsy, revealing that nearly 15% of individuals with FTD receive an epilepsy diagnosis that may precede dementia symptoms. The consistently higher rates of epilepsy in FTD compared to AD at all time points challenge the prevailing focus on epilepsy in AD and suggest that FTD may have an even stronger link to seizure disorders.
The study’s strengths include its use of comprehensive Finnish national health records and neurologist-confirmed diagnoses, which enhance the reliability of the findings. The study’s focus on a Finnish population may limit the generalizability of its conclusions, underscoring the need for replication in more diverse cohorts. There is a higher prevalence of familial FTD related to C9orf72 repeat expansion in the Scandinavian population that also might be related to the epilepsy risk. Nonetheless, these findings highlight the importance of early recognition and management of epilepsy in FTD, which could have meaningful implications for improving quality of life and reducing disability in this younger, vulnerable patient population.
Robert McInnis, MD, is Assistant Professor of Clinical Neurology, Weill Cornell Medical College.
This Finnish case-control study explores the relationship between frontotemporal dementia (FTD) and epilepsy, revealing that individuals with FTD have a higher prevalence of epilepsy compared to those with Alzheimer’s disease (AD) and healthy controls. The findings suggest that epilepsy may precede FTD diagnosis and is more common in FTD than previously recognized, highlighting the need for broader research and clinical awareness of this comorbidity.
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