Liampas Ioannis, Siokas Vasileios, Mourtzi Niki, Charisis Sokratis, Sampatakakis Stefanos N, Foukarakis Ioannis, Hatzimanolis Alex, Ramirez Alfredo, Lambert Jean-Charles, Yannakoulia Mary, Kosmidis Mary H, Dardiotis Efthimios, Hadjigeorgiou Georgios M, Sakka Paraskevi, Rouskas Konstantinos, Scarmeas Nikolaos
Department of Neurology, University Hospital of Larissa, School of Medicine, University of Thessaly, 41100 Larissa, Greece.
1st Department of Neurology, Aiginition Hospital, National and Kapodistrian University of Athens Medical School, 11528 Athens, Greece.
Geriatrics (Basel). 2025 Jan 16;10(1):14. doi: 10.3390/geriatrics10010014.
There is a paucity of evidence on the association between genetic propensity for hippocampal atrophy with cognitive outcomes. Therefore, we examined the relationship of the polygenic risk score for hippocampal atrophy (PRShp) with the incidence of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) as well as the rates of cognitive decline.
Participants were drawn from the population-based HELIAD cohort. Comprehensive neuropsychological assessments were performed at baseline and at follow-up. PRShp was derived from the summary statistics of a large genome-wide association study for hippocampal volume. Cox proportional hazards models as well as generalized estimating equations (GEEs) were used to evaluate the association of PRShp with the combined incidence of aMCI/AD and cognitive changes over time, respectively. All models were adjusted for age, sex, education, and apolipoprotein E (APOE) genotype.
Our analysis included 618 older adults, among whom 73 developed aMCI/AD after an average follow-up of 2.96 ± 0.8 years. Each additional SD of PRShp elevated the relative hazard for incident aMCI/AD by 46%. Participants at the top quartile of PRShp had an almost three times higher risk of converting to aMCI/AD compared to the lowest quartile group. Higher PRShp scores were also linked to steeper global cognitive and memory decline. The impact of PRShp was greater among women and younger adults.
Our findings support the association of PRShp with aMCI/AD incidence and with global cognitive and memory decline over time. The PRS association was sex- and age-dependent, suggesting that these factors should be considered in genetic modelling for AD.
关于海马萎缩的遗传倾向与认知结果之间关联的证据匮乏。因此，我们研究了海马萎缩多基因风险评分（PRShp）与遗忘型轻度认知障碍（aMCI）和阿尔茨海默病（AD）的发病率以及认知衰退率之间的关系。
参与者来自基于人群的HELIAD队列。在基线和随访时进行了全面的神经心理学评估。PRShp源自一项关于海马体积的大型全基因组关联研究的汇总统计数据。分别使用Cox比例风险模型和广义估计方程（GEEs）来评估PRShp与aMCI/AD的合并发病率以及随时间的认知变化之间的关联。所有模型均对年龄、性别、教育程度和载脂蛋白E（APOE）基因型进行了调整。
我们的分析纳入了618名老年人，其中73人在平均随访2.96±0.8年后发生了aMCI/AD。PRShp每增加一个标准差，发生aMCI/AD的相对风险就升高46%。PRShp处于最高四分位数的参与者转换为aMCI/AD的风险几乎是最低四分位数组的三倍。较高的PRShp分数也与更严重的整体认知和记忆衰退有关。PRShp对女性和年轻人的影响更大。
我们的研究结果支持PRShp与aMCI/AD发病率以及随时间的整体认知和记忆衰退之间的关联。PRS关联具有性别和年龄依赖性，表明在AD的遗传建模中应考虑这些因素。
