Alzheimer's disease (AD) symptomatology typically starts with memory deficits. Neurofibrillary tangles - one of the neuropathological hallmarks of AD - first affect the transentorhinal cortex (i.e., Brodmann's area 35 - BA35 and antero-lateral entorhinal cortex), a subregion of the antero-lateral parahippocampal region (also comprising BA36) currently hypothesized to serve as a functional hub representing entities. Here, we tested this hypothesis by investigating whether atrophy of antero-lateral parahippocampal subregions affects memory for entities. Patients with amnestic mild cognitive impairment (aMCI; known to be at high-risk of AD and to present with variable antero-lateral parahippocampal atrophy; N = 17) and healthy older control participants (N = 17) underwent a high-resolution MRI scan of the antero-lateral parahippocampal subregions and a visual object familiarity task, critically including three conditions with increasing need for entity-level representation: (1) letting all fluency cues contribute to familiarity, (2) precluding conceptual fluency, and (3) also precluding perceptual fluency, thereby directly tapping familiarity for entities. In aMCI, right antero-lateral entorhinal cortex specifically contributed to familiarity for entities, an association that was stronger than with familiarity in the 'discriminative' condition (2) (also precluding conceptual fluency, but tested in a viewpoint-dependent fashion as traditionally). In contrast, right BA36 specifically contributed to familiarity in the discriminative condition, an association that appeared marginally stronger than with familiarity for entities. These results shed new light on the functional hierarchy that may exist within the antero-lateral parahippocampal hub. Importantly, familiarity requiring an entity-level representation may specifically target transentorhinal integrity, opening a promising avenue to develop the still-lacking clinical marker of AD-related initial decline.

中文翻译：

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对实体的了解是轻度认知障碍中前外侧内脏萎缩的敏感标志。

阿尔茨海默氏病（AD）症状通常始于记忆缺陷。神经原纤维缠结-AD的神经病理学特征之一-首先影响跨肠上皮层（即Brodmann病区35-BA35和前外侧内嗅皮层），这是目前假设可服务的前外侧海马旁海区（也包括BA36）作为代表实体的功能中心。在这里，我们通过调查前外侧海马旁区域的萎缩是否会影响实体的记忆力来检验该假设。遗忘性轻度认知障碍（aMCI；已知患有AD的高风险且表现为前外侧海马旁萎缩的患者；N = 17）和健康的老年对照组参与者（N = 17）进行了前外侧海马旁亚区的高分辨率MRI扫描和视觉对象熟悉任务，其中关键包括三个条件，这些条件要求实体级表示法的增加：（1 ）让所有流利度提示有助于熟悉度；（2）排除概念性流利度；（3）排除感知性流利度，从而直接利用实体的熟悉度。在aMCI中，右前外侧内嗅皮层特别有助于实体的熟悉，这种关联比“区分性”条件下的熟悉要强（2）（也排除了概念流畅性，但按照传统的观点依赖方式进行了测试） 。相比之下，权利BA36特别有助于提高对区分条件的熟悉程度，似乎比实体熟悉程度强的关联。这些结果为前外侧海马旁枢纽中可能存在的功能层次提供了新的思路。重要的是，需要实体级别代表的熟悉度可以专门针对跨肠胃完整性，从而为发展仍缺乏的与AD相关的初始下降的临床标志物开辟了一条有希望的途径。