A Mitochondrial DNA Haplogroup Defines Patterns of Five-Year Cognitive Change.
A Mitochondrial DNA Haplogroup Defines Patterns of Five-Year Cognitive Change.
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DOI：
10.3233/jad-220298
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发表时间：
2022
影响因子：
4
通讯作者：
Swerdlow, Russell H.
中科院分区：
文献类型：
--
作者：
Watts, Amber;Chalise, Prabhakar;Hu, Jinxiang;Hui, Dongwei;Pa, Judy;Andrews, Shea J.;Michaelis, Elias K.;Swerdlow, Russell H.
线粒体DNA （mtDNA）可能在阿尔茨海默病（AD）和认知能力下降中发挥作用。一种特殊的mtDNA单倍群，单倍群J，在AD患者中比在认知正常的对照组中更常见。我们使用两个mtDNA单倍群，H和J，来预测五年内认知能力的变化。我们假设单倍群J携带者会表现出更少的认知弹性。我们分析了2011年至2020年间参加堪萨斯大学阿尔茨海默病研究中心临床队列的140名认知正常的老年人的数据。我们使用因子分析从11个个体认知测试中创建了三个复合分数（言语记忆、注意力和执行功能）。我们使用了潜在增长曲线模型来描述认知表现和变化的轨迹，调整了年龄、性别、受教育年限和APOE ε4等位基因携带者状态。我们比较了最常见的单倍群H和潜在危险的单倍群J。与单倍群H携带者相比，单倍群J携带者在言语记忆测试中的基线表现明显较低，改善速度较慢。我们没有观察到执行功能或注意力的差异。我们的研究结果强化了mtDNA在认知功能变化中的作用，这一领域与痴呆、言语记忆的风险相关，但与其他认知领域无关。未来的研究应该调查不同的机制，mtDNA可能会影响表现的言语记忆与其他认知领域的单倍群相比。
Mitochondrial DNA (mtDNA) may play a role in Alzheimer’s disease (AD) and cognitive decline. A particular haplogroup of mtDNA, haplogroup J, has been observed more commonly in patients with AD than in cognitively normal controls. We used two mtDNA haplogroups, H and J, to predict change in cognitive performance over five years. We hypothesized that haplogroup J carriers would show less cognitive resilience. We analyzed data from 140 cognitively normal older adults who participated in the University of Kansas Alzheimer’s Disease Research Center clinical cohort between 2011 and 2020. We used factor analysis to create three composite scores (verbal memory, attention, and executive function) from 11 individual cognitive tests. We performed latent growth curve modeling to describe trajectories of cognitive performance and change adjusting for age, sex, years of education, and APOE ε4 allele carrier status. We compared haplogroup H, the most common group, to haplogroup J, the potential risk group. Haplogroup J carriers had significantly lower baseline performance and slower rates of improvement on tests of verbal memory compared to haplogroup H carriers. We did not observe differences in executive function or attention. Our results reinforce the role of mtDNA in changes to cognitive function in a domain associated with risk for dementia, verbal memory, but not with other cognitive domains. Future research should investigate the distinct mechanisms by which mtDNA might affect performance on verbal memory as compared to other cognitive domains across haplogroups.