Kilpeläinen Annemari, Aaltonen Mikko, Aho Kalle, Heikkinen Sami, Kivisild Ave, Lehtonen Adolfina, Leppänen Laura, Rinnankoski Iina, Soppela Helmi, Tervonen Laura, Hartikainen Päivi, Haapasalo Annakaisa, Kälviäinen Reetta, Katisko Kasper, Krüger Johanna, Solje Eino
Institute of Clinical Medicine-Neurology, University of Eastern Finland, Kuopio, Finland.
Neuro Center-Neurology, Kuopio University Hospital, Kuopio, Finland.
JAMA Neurol. 2025 Jun 2. doi: 10.1001/jamaneurol.2025.1358.
Previous studies have described a potential association between epilepsy and frontotemporal dementia (FTD), but no systematic data are available.
To determine whether epilepsy is more prevalent in patients with FTD than in healthy controls (HCs) or patients with Alzheimer disease (AD).
DESIGN, SETTING, AND PARTICIPANTS: 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.
既往研究描述了癫痫与额颞叶痴呆（FTD）之间的潜在关联，但尚无系统性数据。
确定FTD患者中癫痫的患病率是否高于健康对照（HC）或阿尔茨海默病（AD）患者。
设计、背景和参与者：在这项病例对照研究中，我们比较了FTD患者、匹配的HC以及来自芬兰同一地理区域的2个早发性痴呆诊断中心的AD患者中癫痫的患病率和抗癫痫药物（ASM）的购买情况。AD或FTD诊断时间为2010年1月1日至2021年12月31日。数据于2024年1月26日至2025年1月16日进行分析。
主要结局是描述FTD患者中癫痫的患病率，涵盖FTD诊断前10年至诊断后5年的时间段。我们使用国际疾病分类第十版编码来识别所有癫痫患者并追踪ASM的购买情况。
研究队列包括245例FTD患者（121例女性[49.4%]，124例男性[50.6%]；平均[标准差]年龄，65.2[8.7]岁）、2416例匹配的HC（1190例女性[49.3%]，1226例男性[50.7%]；平均[标准差]年龄，65.0[8.5]岁）和1326例AD患者（777例女性[58.6%]，549例男性[41.4%]；平均[标准差]年龄，71.7[9.8]岁）。在FTD诊断前10年，FTD组癫痫的患病率高于HC组（分别为3.3%和0.8%；P = 0.002）和AD组（分别为3.3%和1.4%；P = 0.01）。在诊断当年，FTD患者的患病率为6.5%，HC为1.8%（FTD与HC的差异为4.7个百分点[ppt][95%CI，2.2 - 8.6 ppt]；P < 0.001），AD患者为5.0%（FTD与AD的差异为1.6 ppt[95%CI， - 1.2至5.5 ppt]；P = 0.32）；诊断后5年，FTD患者的患病率为11.2%，HC为2.2%（FTD与HC的差异为9.0 ppt[95%CI，5.0 - 14.6 ppt]；P < 0.001），AD患者为6.9%（FTD与AD的差异为4.2 ppt[95%CI，0 - 10.0 ppt]；P = 0.05）。FTD患者购买ASM的频率显著高于HC（1.8%）和AD患者（4.2%）（FTD与HC的差异为8.4 ppt[95%CI，5.2 - 12.9 ppt]；P < 0.001；FTD与AD的差异为6.1 ppt[95%CI，2.6 - 10.6 ppt]；P < 0.001），且在研究期间有所增加。
这项病例对照研究发现，与HC和AD患者相比，FTD患者中癫痫的患病率更高且ASM使用增加，提示癫痫异常与FTD的病理生理学之间存在关联。有必要进一步研究癫痫和FTD病理生理机制中潜在的重叠情况。
