National Institute of Clinical Neurosciences, Department of Neurology Budapest, Hungary; Semmelweis University, Department of Anatomy Histology and Embryology, Budapest, Hungary.
National Institute of Clinical Neurosciences, Department of Neurology Budapest, Hungary; Semmelweis University, School of PhD Studies, Budapest, Hungary.
Clin Neurophysiol. 2021 Aug;132(8):1982-1989. doi: 10.1016/j.clinph.2021.03.050. Epub 2021 May 8.
While many studies suggest that patients with Alzheimer's disease have a higher chance for developing epileptic seizures, only a few studies are available examining independent epileptic discharges. The major aims of our study was to determine the prevalence of subclinical epileptiform activity (SEA) in AD compared to healthy elderly controls with the hypothesis that SEA is more frequent in AD than in cognitively normal individuals. Another aim was to analyze the effect of baseline SEA captured with electroencephalography on the progression of the disease with longitudinal cognitive testing.
We investigated 52 Alzheimer patients with no history of epileptic seizures and 20 healthy individuals. All participants underwent a 24-hour electroencephalography, neurology, neuroimaging and neuropsychology examination. Two independent raters analyzed visually the electroencephalograms and both raters were blind to the diagnoses. Thirty-eight Alzheimer patients were enrolled in a 3-year long prospective follow-up study with yearly repeated cognitive evaluation.
Subclinical epileptiform discharges were recorded significantly (p:0.018) more frequently in Alzheimer patients (54%) than in healthy elderly (25%). Epileptiform discharges were associated with lower performance scores in memory. Alzheimer patients with spikes showed 1.5-times faster decline in global cognitive scores than patients without (p < 0.001). The decline in cognitive performance scores showed a significant positive correlation with spike frequency (r:+0.664; p < 0.001).
Subclinical epileptiform activity occurs in half of Alzheimer patients who have never suffered epileptic seizures. Alzheimer patients with subclinical epileptiform activity showed accelerated cognitive decline with a strong relation to the frequency and spatial distribution (left temporal) of spikes.
Our findings suggest the prominent role of epileptiform discharges in the pathomechanism of Alzheimer's disease which might serve as potential therapeutic target.
虽然许多研究表明阿尔茨海默病患者发生癫痫发作的可能性更高,但仅有少数研究检查了独立的癫痫放电。我们研究的主要目的是确定与健康老年对照组相比,AD 患者亚临床癫痫样活动(SEA)的患病率,假设 SEA 在 AD 中比在认知正常个体中更为常见。另一个目的是分析脑电图记录的基线 SEA 对疾病进展的影响,进行纵向认知测试。
我们调查了 52 例无癫痫发作史的阿尔茨海默病患者和 20 例健康个体。所有参与者均接受了 24 小时脑电图、神经病学、神经影像学和神经心理学检查。两位独立的评估者对脑电图进行了视觉分析,并且两位评估者均对诊断结果不知情。38 例阿尔茨海默病患者被纳入一项为期 3 年的前瞻性随访研究,每年重复进行认知评估。
亚临床癫痫样放电在阿尔茨海默病患者(54%)中记录明显更为频繁(p:0.018),明显高于健康老年人(25%)。癫痫样放电与记忆力的较低评分相关。具有棘波的阿尔茨海默病患者的总体认知评分下降速度比无棘波患者快 1.5 倍(p<0.001)。认知表现评分的下降与棘波频率呈显著正相关(r:+0.664;p<0.001)。
从未遭受过癫痫发作的阿尔茨海默病患者中有一半存在亚临床癫痫样活动。具有亚临床癫痫样活动的阿尔茨海默病患者的认知能力下降加速,与棘波的频率和空间分布(左颞叶)有密切关系。
我们的发现表明癫痫样放电在阿尔茨海默病的发病机制中起重要作用,这可能成为潜在的治疗靶点。