Ripperger Hayley S, Reed Rebecca G, Kang Chaeryon, Lesnovskaya Alina, Aghjayan Sarah L, Huang Haiqing, Wan Lu, Sutton Bradley P, Oberlin Lauren, Collins Audrey M, Burns Jeffrey M, Vidoni Eric D, Kramer Arthur F, McAuley Edward, Hillman Charles H, Grove George A, Jakicic John M, Erickson Kirk I
Department of Psychology, University of Pittsburgh, Pittsburgh, PA, United States.
Department of Psychiatry, University of Pittsburgh, Pittsburgh, PA, United States.
Front Aging Neurosci. 2024 Dec 19;16:1466328. doi: 10.3389/fnagi.2024.1466328. eCollection 2024.
Age-related hippocampal atrophy is associated with memory loss in older adults, and certain hippocampal subfields are more vulnerable to age-related atrophy than others. Cardiorespiratory fitness (CRF) may be an important protective factor for preserving hippocampal volume, but little is known about how CRF relates to the volume of specific hippocampal subfields, and whether associations between CRF and hippocampal subfield volumes are related to episodic memory performance. To address these gaps, the current study evaluates the associations among baseline CRF, hippocampal subfield volumes, and episodic memory performance in cognitively unimpaired older adults from the Investigating Gains in Neurocognition Trial of Exercise (IGNITE) (NCT02875301).
Participants ( = 601, ages 65-80, 72% female) completed assessments including a graded exercise test measuring peak oxygen comsumption (VO) to assess CRF, cognitive testing, and high-resolution magnetic resonance imaging of the hippocampus processed with Automated Segmentation of Hippocampal Subfields (ASHS). Separate linear regression models examined whether CRF was associated with hippocampal subfield volumes and whether those assocations were moderated by age or sex. Mediation models examined whether hippocampal volumes statistically mediated the relationship between CRF and episodic memory performance. Covariates included age, sex, years of education, body mass index, estimated intracranial volume, and study site.
Higher CRF was significantly associated with greater total left ( = 5.82, = 0.039) and total right ( = 7.64, = 0.006) hippocampal volume, as well as greater left CA2 ( = 0.14, = 0.022) and dentate gyrus (DG; = 2.34, = 0.031) volume, and greater right CA1 ( = 3.99, = 0.011), CA2 ( = 0.15, = 0.002), and subiculum ( = 1.56, = 0.004) volume. Sex significantly moderated left DG volume ( = -4.26, = 0.017), such that the association was positive and significant only for males. Total left hippocampal volume [indirect effect = 0.002, 95% CI (0.0002, 0.00), = 0.027] and right subiculum volume [indirect effect = 0.002, 95% CI (0.0007, 0.01), = 0.006] statistically mediated the relationship between CRF and episodic memory performance.
While higher CRF was significantly associated with greater total hippocampal volume, CRF was not associated with all underlying subfield volumes. Our results further demonstrate the relevance of the associations between CRF and hippocampal volume for episodic memory performance. Finally, our results suggest that the regionally-specific effects of aging and Alzheimer's disease on hippocampal subfields could be mitigated by maintaining higher CRF in older adulthood.
与年龄相关的海马萎缩与老年人的记忆丧失有关，并且某些海马亚区比其他亚区更容易受到与年龄相关的萎缩影响。心肺适能（CRF）可能是保留海马体积的一个重要保护因素，但关于CRF与特定海马亚区体积之间的关系，以及CRF与海马亚区体积之间的关联是否与情景记忆表现相关，我们知之甚少。为了填补这些空白，本研究评估了来自运动神经认知增益调查试验（IGNITE）（NCT02875301）的认知未受损老年人的基线CRF、海马亚区体积和情景记忆表现之间的关联。
参与者（n = 601，年龄65 - 80岁，72%为女性）完成了多项评估，包括一项测量峰值耗氧量（VO）以评估CRF的分级运动测试、认知测试，以及使用海马亚区自动分割（ASHS）处理的海马高分辨率磁共振成像。单独的线性回归模型检验了CRF是否与海马亚区体积相关，以及这些关联是否受年龄或性别的调节。中介模型检验了海马体积是否在统计学上介导了CRF与情景记忆表现之间的关系。协变量包括年龄、性别、受教育年限、体重指数、估计颅内体积和研究地点。
较高的CRF与更大的左侧海马总体积（β = 5.82，p = 0.039）和右侧海马总体积（β = 7.64，p = 0.006）显著相关，以及与更大的左侧CA2体积（β = 0.14，p = 0.022）、齿状回（DG；β = 2.34，p = 0.031）体积，和更大的右侧CA1体积（β = 3.99，p = 0.011）、CA2体积（β = 0.15，p = 0.002）和下托体积（β = 1.56，p = 0.004）相关。性别显著调节了左侧DG体积（β = -4.26，p = 0.017），使得该关联仅对男性为正且显著。左侧海马总体积[间接效应 = 0.002，95%置信区间（0.0002，0.00），p = 0.027]和右侧下托体积[间接效应 = 0.002，95%置信区间（0.0007，0.01），p = 0.006]在统计学上介导了CRF与情景记忆表现之间的关系。
虽然较高的CRF与更大的海马总体积显著相关，但CRF与所有潜在的亚区体积并不都相关。我们的结果进一步证明了CRF与海马体积之间的关联对情景记忆表现的相关性。最后，我们的结果表明，在成年后期维持较高的CRF可以减轻衰老和阿尔茨海默病对海马亚区的区域特异性影响。
