Sheng Jintao, Trelle Alexandra N, Romero America, Park Jennifer, Tran Tammy T, Sha Sharon J, Andreasson Katrin I, Wilson Edward N, Mormino Elizabeth C, Wagner Anthony D
Department of Psychology, Stanford University, Stanford, CA, USA.
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
Sci Adv. 2025 Jun 13;11(24):eads4206. doi: 10.1126/sciadv.ads4206.
Effective memory formation declines in human aging. Diminished neural selectivity-reduced differential responses to preferred versus nonpreferred stimuli-may contribute to memory decline, but its drivers remain unclear. We investigated the effects of top-down attention and preclinical Alzheimer's disease (AD) pathology on neural selectivity in 166 cognitively unimpaired older participants using functional magnetic resonance imaging during a word-face/word-place associative memory task. During learning, neural selectivity in place- and, to a lesser extent, face-selective regions was greater for subsequently remembered than forgotten events; positively scaled with variability in dorsal attention network activity, within and across individuals; and negatively related to AD pathology, evidenced by elevated plasma phosphorylated Tau (pTau). Path analysis revealed that neural selectivity mediated the effects of age, attention, and pTau on memory. These data reveal multiple pathways that contribute to memory differences among older adults-AD-independent reductions in top-down attention and AD-related pathology alter the precision of cortical representations of events during experience, with consequences for remembering.
有效的记忆形成在人类衰老过程中会下降。神经选择性降低——对偏好刺激与非偏好刺激的差异反应减少——可能导致记忆衰退，但其驱动因素尚不清楚。我们在一项单词-面孔/单词-地点联想记忆任务中，使用功能磁共振成像研究了自上而下的注意力和临床前阿尔茨海默病（AD）病理对166名认知未受损的老年参与者神经选择性的影响。在学习过程中，与随后被遗忘的事件相比，在地点选择性区域以及程度较轻的面孔选择性区域中，对随后被记住的事件的神经选择性更强；与背侧注意力网络活动在个体内部和个体之间的变异性呈正相关；与AD病理呈负相关，血浆磷酸化 Tau（pTau）升高证明了这一点。路径分析表明，神经选择性介导了年龄、注意力和pTau对记忆的影响。这些数据揭示了导致老年人记忆差异的多种途径——与AD无关的自上而下注意力的减少和与AD相关的病理改变了体验过程中事件皮层表征的精度，从而影响记忆。
