Cognitive dysfunction in naturally occurring canine idiopathic epilepsy

Globally, epilepsy is a common serious brain disorder. In addition to seizure activity, epilepsy is associated with cognitive impairments including static cognitive impairments present at onset, progressive seizure-induced impairments and co-morbid dementia. Epilepsy occurs naturally in domestic dogs but its impact on canine cognition has yet to be studied, despite canine cognitive dysfunction (CCD) recognised as a spontaneous model of dementia. Here we use data from a psychometrically validated tool, the canine cognitive dysfunction rating (CCDR) scale, to compare cognitive dysfunction in dogs diagnosed with idiopathic epilepsy (IE) with controls while accounting for age. An online cross-sectional study resulted in a sample of 4051 dogs, of which n = 286 had been diagnosed with IE. Four factors were significantly associated with a diagnosis of CCD (above the diagnostic cut-off of CCDR ≥50): (i) epilepsy diagnosis: dogs with epilepsy were at higher risk; (ii) age: older dogs were at higher risk; (iii) weight: lighter dogs (kg) were at higher risk; (iv) training history: dogs with more exposure to training activities were at lower risk. Impairments in memory were most common in dogs with IE, but progression of impairments was not observed compared to controls. A significant interaction between epilepsy and age was identified, with IE dogs exhibiting a higher risk of CCD at a young age, while control dogs followed the expected pattern of low-risk throughout middle age, with risk increasing exponentially in geriatric years. Within the IE sub-population, dogs with a history of cluster seizures and high seizure frequency had higher CCDR scores. The age of onset, nature and progression of cognitive impairment in the current IE dogs appear divergent from those classically seen in CCD. Longitudinal monitoring of cognitive function from seizure onset is required to further characterise these impairments.

癫痫是全球范围内常见的严重脑部疾病。除癫痫发作症状外，该病还可伴随多种认知功能损害，包括发病时即存在的静态认知损伤、癫痫发作诱发的进行性认知损害，以及共病性痴呆。癫痫可自然发生于家养犬只中，但尽管犬类认知功能障碍（canine cognitive dysfunction, CCD）已被公认是痴呆的自发模型，癫痫对犬类认知功能的影响迄今仍未得到充分研究。本研究采用经心理测量学验证的工具——犬类认知功能障碍评定量表（canine cognitive dysfunction rating scale, CCDR）的数据，在控制年龄因素的前提下，对比特发性癫痫（idiopathic epilepsy, IE）患犬与对照组犬只的认知功能障碍情况。本研究通过一项线上横断面研究纳入4051只犬只作为研究样本，其中286只被确诊为特发性癫痫。以CCDR量表临界值≥50作为CCD确诊标准，共有四项因素与CCD确诊显著相关：（i）癫痫诊断：患癫痫的犬只患病风险更高；（ii）年龄：老龄犬只患病风险更高；（iii）体重：体重较轻的犬只（单位：千克）患病风险更高；（iv）训练经历：接受更多训练活动的犬只患病风险更低。特发性癫痫患犬最常见的认知损害为记忆障碍，但与对照组相比未观察到认知损害的进展。研究还发现癫痫诊断与年龄存在显著交互作用：特发性癫痫患犬在年轻时即表现出更高的CCD患病风险，而对照组犬只则呈现预期的风险模式——中年时期风险维持低位，至老年阶段风险呈指数级上升。在特发性癫痫亚群中，有癫痫丛集发作史及发作频率较高的犬只，其CCDR量表得分更高。本研究中特发性癫痫患犬的认知损害发病年龄、损害特征与病程进展，均与经典犬类认知功能障碍病例存在差异。未来需开展从癫痫发作起始即进行的认知功能纵向监测，以进一步明确此类认知损害的特征。