Gorbach Tetiana, Pudas Sara, Bartrés-Faz David, Brandmaier Andreas M, Düzel Sandra, Henson Richard N, Idland Ane-Victoria, Lindenberger Ulman, Macià Bros Didac, Mowinckel Athanasia M, Solé-Padullés Cristina, Sørensen Øystein, Walhovd Kristine B, Watne Leiv Otto, Westerhausen René, Fjell Anders M, Nyberg Lars
Department of Integrative Medical Biology Umeå University Umeå Sweden.
Umeå Center for Functional Brain Imaging Umeå University Umeå Sweden.
Alzheimers Dement (Amst). 2020 Sep 28;12(1):e12110. doi: 10.1002/dad2.12110. eCollection 2020.
The apolipoprotein E () ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic-memory decline in non-demented individuals remains unclear.
We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)-derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European consortium.
The change-change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, = .007; non-carriers: N = 467, r = 0.073, = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, = .013]. A similar trend toward a stronger change-change relation for carriers was seen in a subsample with more than two assessments.
These findings provide evidence for a difference in hippocampus-memory association between ε4 carriers and non-carriers, thus highlighting how genetic factors modulate the translation of the AD-related pathophysiological cascade into cognitive deficits.
载脂蛋白E（）ε4等位基因是阿尔茨海默病（AD）、加速认知衰老和海马萎缩的主要遗传风险因素，但其对非痴呆个体中海马萎缩与情景记忆衰退之间关联的影响尚不清楚。
我们分析了来自欧洲联盟的748名个体（基线年龄55至90岁，50%为女性）的纵向（两至六次观察）磁共振成像（MRI）得出的海马体积和情景记忆。
海马体积与记忆的变化-变化关联仅在ε4携带者中显著（N = 173，r = 0.21，= .007；非携带者：N = 467，r = 0.073，= .117）。携带者的线性关系显著更陡峭[t(629) = 2.4，= .013]。在有超过两次评估的子样本中，携带者也呈现出更强的变化-变化关系的类似趋势。
这些发现为ε4携带者和非携带者之间海马-记忆关联的差异提供了证据，从而突出了遗传因素如何调节与AD相关的病理生理级联向认知缺陷的转化。
