Xu Jingjing, Guan Xiaojun, Wen Jiaqi, Zhang Minming, Xu Xiaojun
Department of Radiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Aging Neurosci. 2022 Oct 31;14:943702. doi: 10.3389/fnagi.2022.943702. eCollection 2022.
Understanding genetic influences on Alzheimer's disease (AD) may improve early identification. Polygenic hazard score (PHS) is associated with the age of AD onset and cognitive decline. It interacts with other risk factors, but the nature of such combined effects remains poorly understood.
We examined the effect of genetic risk and hippocampal atrophy pattern on episodic memory in a sample of older adults ranging from cognitively normal to those diagnosed with AD using structural MRI. Participants included 51 memory unimpaired normal control (NC), 69 mild cognitive impairment (MCI), and 43 AD adults enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI). Hierarchical linear regression analyses examined the main and interaction effects of hippocampal subfield volumes and PHS, indicating genetic risk for AD, on a validated episodic memory composite score. Diagnosis-stratified models further assessed the role of PHS.
Polygenic hazard score moderated the relationship between right fimbria/hippocampus volume ratio and episodic memory, such that patients with high PHS and lower volume ratio had lower episodic memory composite scores [ΔF = 6.730, = 0.011, Δ = 0.059]. This effect was also found among individuals with MCI [ΔF = 4.519, = 0.038, Δ = 0.050]. In contrast, no interaction effects were present for those NC or AD individuals. A follow-up mediation analysis also indicated that the right fimbria/hippocampus volume ratio might mediate the link between PHS and episodic memory performance in the MCI group, whereas no mediation effects were present for those NC or AD individuals.
These findings suggest that the interaction between AD genetic risk and hippocampal subfield volume ratio increases memory impairment among older adults. Also, the results highlighted a potential pathway in which genetic risk affects memory by degrading hippocampal subfield volume ratio in cognitive decline subjects.
了解基因对阿尔茨海默病（AD）的影响可能有助于早期识别。多基因风险评分（PHS）与AD发病年龄及认知衰退有关。它与其他风险因素相互作用，但其联合效应的本质仍知之甚少。
我们使用结构磁共振成像（MRI），在从认知正常到被诊断为AD的老年人样本中，研究了遗传风险和海马萎缩模式对情景记忆的影响。参与者包括51名记忆未受损的正常对照（NC）、69名轻度认知障碍（MCI）和43名参与阿尔茨海默病神经影像倡议（ADNI）的AD患者。分层线性回归分析研究了海马亚区体积和PHS（表明AD的遗传风险）对经过验证的情景记忆综合评分的主要和交互作用。诊断分层模型进一步评估了PHS的作用。
多基因风险评分调节了右侧伞/海马体积比与情景记忆之间的关系，即PHS高且体积比低的患者情景记忆综合评分较低[ΔF = 6.730，P = 0.011，ΔR² = 0.059]。在MCI个体中也发现了这种效应[ΔF = 4.519，P = 0.038，ΔR² = 0.050]。相比之下，NC或AD个体中不存在交互作用。一项后续中介分析还表明，右侧伞/海马体积比可能介导了MCI组中PHS与情景记忆表现之间的联系，而NC或AD个体中不存在中介效应。
这些发现表明，AD遗传风险与海马亚区体积比之间的相互作用会增加老年人的记忆损害。此外，结果突出了一条潜在途径，即遗传风险通过降低认知衰退受试者的海马亚区体积比来影响记忆。
