Demographic and disease factors are associated with cognitive deficits and postoperative cognitive declines in adults with pharmacoresistant temporal lobe epilepsy (TLE), but the role of genetic factors in cognition in TLE is not well understood. Polygenic scores (PGS) for neurological and neuropsychiatric disorders and IQ have been associated with cognition in patient and healthy populations. In this exploratory study, we examined the relationship between PGS for Alzheimer’s disease (AD), depression, and IQ and cognitive outcomes in adults with TLE. 202 adults with pharmacoresistant TLE had genotyping and completed neuropsychological evaluations as part of a presurgical work-up. A subset (n = 116) underwent temporal lobe resection and returned for postoperative cognitive testing. Logistic regression was used to determine if PGS for AD, depression, and IQ predicted baseline domain-specific cognitive function and cognitive phenotypes as well as postoperative language and memory decline. No significant findings survived correction for multiple comparisons. Prior to correction, higher PGS for AD and depression (i.e., increased genetic risk for the disorder), but lower PGS for IQ (i.e., decreased genetic likelihood of high IQ) appeared possibly associated with baseline cognitive impairment in TLE. In comparison, higher PGS for AD and IQ appeared as possible risk factors for cognitive decline following temporal lobectomy, while the possible relationship between PGS for depression and post-operative cognitive outcome was mixed. We did not observe any relationships of large effect between PGS and cognitive function or postsurgical outcome; however, results highlight several promising trends in the data that warrant future investigation in larger samples better powered to detect small genetic effects.

中文翻译：

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颞叶癫痫的多基因负担及其与基线认知功能和术后认知结果的关系

人口统计学和疾病因素与耐药性颞叶癫痫 (TLE) 成人患者的认知缺陷和术后认知能力下降有关，但遗传因素在 TLE 认知中的作用尚不清楚。神经系统和神经精神疾病以及智商的多基因评分 (PGS) 与患者和健康人群的认知相关。在这项探索性研究中，我们研究了 PGS 与阿尔茨海默病 (AD)、抑郁症以及 TLE 成人智商和认知结果之间的关系。作为术前检查的一部分，202 名患有耐药性 TLE 的成人进行了基因分型并完成了神经心理学评估。一个子集（n = 116）接受了颞叶切除术并返回进行术后认知测试。 Logistic 回归用于确定 AD、抑郁症和 IQ 的 PGS 是否可以预测基线特定领域认知功能和认知表型以及术后语言和记忆力下降。经过多重比较校正后，没有发现任何重大发现。在校正之前，AD 和抑郁症的 PGS 较高（即，该疾病的遗传风险增加），但 IQ 的 PGS 较低（即，高智商的遗传可能性降低）似乎可能与 TLE 的基线认知障碍有关。相比之下，AD 和 IQ 较高的 PGS 似乎是颞叶切除术后认知能力下降的可能危险因素，而抑郁症 PGS 与术后认知结果之间的可能关系是复杂的。我们没有观察到 PGS 与认知功能或术后结果之间存在任何重大影响的关系；然而，结果凸显了数据中的几个有希望的趋势，这些趋势值得未来对更大的样本进行研究，以更好地检测微小的遗传效应。