Importance  The extent of dorsolateral prefrontal cortex (DLPFC) plasticity in Alzheimer disease (AD) and its association with working memory are not known.

Objectives  To determine whether participants with AD had impaired DLPFC plasticity compared with healthy control participants, to compare working memory between participants with AD and controls, and to determine whether DLPFC plasticity was associated with working memory.

Design, Setting, and Participants  This cross-sectional study included 32 participants with AD who were 65 years or older and met diagnostic criteria for dementia due to probable AD with a score of at least 17 on the Mini-Mental State Examination and 16 age-matched control participants. Participants were recruited from a university teaching hospital from May 2013 to October 2016.

Main Outcomes and Measures  Plasticity of the DLPFC measured as potentiation of cortical-evoked activity using paired associative stimulation (a combination of peripheral nerve electrical stimulation and transcranial magnetic stimulation) combined with electroencephalography. Working memory was assessed with the n-back task (1- and 2-back) and measured using the A’ statistic.

Results  Among the 32 participants with AD, 17 were women and 15 were men (mean [SD] age, 76.3 [6.3] years); among the 16 controls, 8 were men and 8 were women (mean [SD] age, 76.4 [5.1] years). Participants with AD had impaired DLPFC plasticity (mean [SD] potentiation, 1.18 [0.25]) compared with controls (mean [SD] potentiation, 1.40 [0.35]; F_1,44 = 5.90; P = .02; between-group comparison, Cohen d = 0.77; P = .01). Participants with AD also had impaired performances on the 1-back condition (mean [SD] A′ = 0.47 [0.30]) compared with controls (mean [SD] A′ = 0.96 [0.01]; Cohen d = 1.86; P < .001), with similar findings for participants with AD on the 2-back condition (mean [SD] A’ = 0.29 [0.2]) compared with controls (mean [SD], A′ = 0.85 [0.18]; Cohen d = 2.83; P < .001). Plasticity of DLPFC was positively associated with working memory performance on the 1-back A′ (parameter estimate B [SE] = 0.32 [0.13]; standardized β = 0.29; P = .02) and 2-back A′ (B [SE] = 0.43 [0.15]; β = 0.39; P = .006) across both groups after controlling for age, education, and attention.

Conclusions and Relevance  This study demonstrated impaired in vivo DLPFC plasticity in patients with AD. The findings support the use of DLPFC plasticity as a measure of DLPFC function and a potential treatment target to enhance DLPFC function and working memory in patients with AD.

重要性  阿尔茨海默病（AD）的背外侧前额叶皮层（DLPFC）可塑性的程度及其与工作记忆的关系尚不清楚。

目的  确定与健康对照组相比，AD参与者是否受损DLPFC可塑性，比较具有AD和对照的参与者的工作记忆，并确定DLPFC可塑性是否与工作记忆有关。

设计，背景和参与者  这项横断面研究包括32位65岁或65岁以上的AD参与者，这些人由于可能的AD符合痴呆症的诊断标准，在最低精神状态检查中得分至少为17分，在16岁以上年龄中，匹配的对照参与者。参与者于2013年5月至2016年10月从大学教学医院招募。

主要结果和措施  DLPFC的可塑性是通过配对联想刺激（周围神经电刺激和经颅磁刺激的组合）结合脑电图测量的皮层诱发活动的增强来测量的。工作记忆用n后退任务（1后退和2后退）评估，并使用A'统计量度。

结果  32名AD参与者中，女性17名，男性15名（平均[SD]年龄为76.3 [6.3]岁）；在16位对照中，男性8位，女性8位（平均[SD]年龄，为76.4 [5.1]岁）。与对照组相比，AD参与者的DLPFC可塑性降低（平均[SD]增强，1.18 [0.25]）；对照组（平均[SD]增强，1.40 [0.35]）；F _1,44  = 5.90；P  = .02；组间比较，Cohen d  = 0.77；P  = 0.01）。与对照组相比，患有AD的参与者在1-back状态下的表现也受损（平均[SD] A '= 0.47 [0.30]）（平均[SD] A '= 0.96 [0.01]； Cohen d  = 1.86；P <0.001），与参与者AD上的2反条件类似的发现（平均[SD] A”  = 0.29 [0.2]）与对照（平均值[SD]相比，甲'= 0.85 [0.18];科恩d  = 2.83；P  <.001）。DLPFC的可塑性与1背A ′（参数估计B [SE] = 0.32 [0.13]；标准β= 0.29；P  = .02）和2背A ′（B  [SE ] = 0.43 [0.15]；β= 0.39；P  = 0.006）在控制了年龄，教育程度和注意力后，两组之间的差异。

结论与相关性  这项研究证明了AD患者体内DLPFC的可塑性受损。这些发现支持使用DLPFC可塑性作为DLPFC功能的一种指标，并成为增强AD患者DLPFC功能和工作记忆的潜在治疗目标。