Importance Understanding the mechanisms of delusion formation in Alzheimer disease (AD) could inform the development of therapeutic interventions. It has been suggested that delusions arise as a consequence of false memories. Objective To investigate whether delusions in AD are associated with false recognition, and whether higher rates of false recognition and the presence of delusions are associated with lower regional brain volumes in the same brain regions. Design, Setting, and Participants Since the Alzheimer's Disease Neuroimaging Initiative (ADNI) launched in 2004, it has amassed an archive of longitudinal behavioral and biomarker data. This cross-sectional study used data downloaded in 2020 from ADNI participants with an AD diagnosis at baseline or follow-up. Data analysis was performed between June 24, 2020, and September 21, 2021. Exposure Enrollment in the ADNI. Main Outcomes and Measures The main outcomes included false recognition, measured with the 13-item Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog 13) and the Rey Auditory Verbal Learning Test (RAVLT) and volume of brain regions corrected for total intracranial volume. Behavioral data were compared for individuals with delusions in AD and those without using independent-samples t tests or Mann-Whitney nonparametric tests. Significant findings were further explored using binary logistic regression modeling. For neuroimaging data region of interest analyses using t tests, Poisson regression modeling or binary logistic regression modeling and further exploratory, whole-brain voxel-based morphometry analyses were carried out to explore the association between regional brain volume and false recognition or presence of delusions. Results Of the 2248 individuals in the ADNI database, 728 met the inclusion criteria and were included in this study. There were 317 (43.5%) women and 411 (56.5%) men. Their mean (SD) age was 74.8 (7.4) years. The 42 participants with delusions at baseline had higher rates of false recognition on the ADAS-Cog 13 (median score, 3; IQR, 1 to 6) compared with the 549 control participants (median score, 2; IQR, 0 to 4; U = 9398.5; P = .04). False recognition was not associated with the presence of delusions when confounding variables were included in binary logistic regression models. An ADAS-Cog 13 false recognition score was inversely associated with left hippocampal volume (odds ratio [OR], 0.91 [95% CI, 0.88-0.94], P < .001), right hippocampal volume (0.94 [0.92-0.97], P < .001), left entorhinal cortex volume (0.94 [0.91-0.97], P < .001), left parahippocampal gyrus volume (0.93 [0.91-0.96], P < .001), and left fusiform gyrus volume (0.97 [0.96-0.99], P < .001). There was no overlap between locations associated with false recognition and those associated with delusions. Conclusions and Relevance In this cross-sectional study, false memories were not associated with the presence of delusions after accounting for confounding variables, and no indication for overlap of neural networks for false memories and delusions was observed on volumetric neuroimaging. These findings suggest that delusions in AD do not arise as a direct consequence of misremembering, lending weight to ongoing attempts to delineate specific therapeutic targets for treatment of psychosis.

中文翻译：

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阿尔茨海默病中错误记忆和妄想之间的关联。


重要性 了解阿尔茨海默病 (AD) 妄想形成的机制可以为治疗干预措施的开发提供信息。有人认为，妄想是由于错误记忆而产生的。目的 探讨 AD 中的妄想是否与错误识别相关，以及较高的错误识别率和妄想的存在是否与同一脑区较低的区域脑容量相关。设计、设置和参与者 自 2004 年启动阿尔茨海默病神经影像计划 (ADNI) 以来，它已经积累了纵向行为和生物标记数据的档案。这项横断面研究使用了 2020 年从基线或随访时诊断为 AD 的 ADNI 参与者下载的数据。数据分析于 2020 年 6 月 24 日至 2021 年 9 月 21 日期间进行。ADNI 中的暴露登记。主要结果和测量 主要结果包括错误识别，通过 13 项阿尔茨海默氏病评估量表认知分量表 (ADAS-Cog 13) 和雷伊听觉言语学习测试 (RAVLT) 进行测量，以及根据颅内总体积校正的大脑区域体积。对患有 AD 妄想的个体和未使用独立样本 t 检验或曼-惠特尼非参数检验的个体的行为数据进行了比较。使用二元逻辑回归模型进一步探讨了重要发现。对于使用 t 检验、泊松回归模型或二元逻辑回归模型进行神经影像数据感兴趣区域分析，以及进一步探索性的、基于全脑体素的形态测量分析，以探索区域脑体积与错误识别或妄想存在之间的关联。 结果 ADNI 数据库中的 2248 人中有 728 人符合纳入标准并纳入本研究。其中女性 317 名（43.5%），男性 411 名（56.5%）。他们的平均 (SD) 年龄为 74.8 (7.4) 岁。与 549 名对照参与者（中位数分 2；IQR 0 至 4；U = 9398.5；P = .04)。当二元逻辑回归模型中包含混杂变量时，错误识别与妄想的存在无关。 ADAS-Cog 13 错误识别评分与左侧海马体积（比值比 [OR]，0.91 [95% CI，0.88-0.94]，P < .001）、右侧海马体积（0.94 [0.92-0.97]， P < .001)、左内嗅皮层体积 (0.94 [0.91-0.97], P < .001)、左海马旁回体积 (0.93 [0.91-0.96], P < .001) 和左梭状回体积 (0.97 [ 0.96-0.99]，P < .001）。与错误识别相关的位置和与妄想相关的位置之间没有重叠。结论和相关性在这项横断面研究中，在考虑了混杂变量后，错误记忆与妄想的存在无关，并且在体积神经影像中没有观察到错误记忆和妄想的神经网络重叠的迹象。这些研究结果表明，AD 中的妄想并不是记忆错误的直接结果，这为持续不断的尝试确定精神病治疗的具体治疗目标提供了依据。