常染色体显性阿尔茨海默病的认知结局：来自携带有早老素-1 E280A 突变的哥伦比亚家系的综合综述。
Cognitive Outcomes in Autosomal-Dominant Alzheimer's Disease: A Comprehensive Review from a Colombian Kindred with the Presenilin-1 E280A Mutation.
机构信息
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
出版信息
J Alzheimers Dis. 2024;101(2):397-415. doi: 10.3233/JAD-240360.
BACKGROUND
The largest identified kindred worldwide with a single mutation causing autosomal-dominant Alzheimer's disease (ADAD) is a family from Antioquia, Colombia, carrying the Presenilin-1 (PSEN1) E280A (Paisa) mutation. The majority of mutation carriers develop dementia, typically commencing in their late 30 s, with a median onset age of 49 years. Cognitive decline is a hallmark feature.
OBJECTIVE
This review synthesizes the existing literature on neuropsychological assessments in PSEN1 E280A mutation carriers throughout their lifespan. We provide a comprehensive overview of cognitive outcomes in this unique population.
METHODS
We reviewed and integrated the published research, analyzing studies on neuropsychological assessments in PSEN1 E280A carriers. Our focus was on measures of verbal, semantic, episodic, and spatial memory, and encompassed other cognitive domains such as language, attention, visuospatial memory, and executive functioning.
RESULTS
Verbal, semantic, episodic, and spatial memory emerged as the most sensitive indicators of preclinical changes in PSEN1 E280A carriers. Inconsistencies were noted in findings from tests assessing language, attention, visuospatial memory, and executive functioning, suggesting potential limitations in detecting early cognitive changes in PSEN1 mutation carriers. Specific cognitive tasks developed for this population proved effective but underutilized.
CONCLUSIONS
The review underscores the importance of continued test development tailored to detect early cognitive changes in PSEN1 E280A carriers, potentially enhancing ADAD screening. Furthermore, investigating ADAD mutations in children may identify early changes in AD and enhance our understanding of neuropsychological functioning across the lifespan. This synthesis provides valuable insights for researchers, clinicians, and policymakers engaged in the study and management of ADAD.
背景
全球范围内，携带单一突变导致常染色体显性阿尔茨海默病（ADAD）的最大家族是来自哥伦比亚安蒂奥基亚的一个家族，携带早老素-1（PSEN1）E280A（Paisa）突变。大多数突变携带者会发展为痴呆症，通常在 30 多岁开始发病，中位发病年龄为 49 岁。认知能力下降是其主要特征之一。
目的
本综述综合了 PSEN1 E280A 突变携带者在整个生命周期中的神经心理学评估的现有文献。我们全面概述了这一独特人群的认知结果。
方法
我们对已发表的研究进行了回顾和整合，分析了 PSEN1 E280A 携带者的神经心理学评估研究。我们的重点是言语、语义、情景和空间记忆等认知领域的测量，还包括语言、注意力、视空间记忆和执行功能等其他认知领域。
结果
言语、语义、情景和空间记忆是 PSEN1 E280A 携带者出现临床前变化的最敏感指标。评估语言、注意力、视空间记忆和执行功能的测试结果存在不一致，表明在检测 PSEN1 突变携带者的早期认知变化方面存在潜在局限性。针对该人群开发的特定认知任务虽然有效，但使用不足。
结论
本综述强调了继续开发针对 PSEN1 E280A 携带者的特定认知测试的重要性，这可能有助于 ADAD 的筛查。此外，对 AD 儿童的 AD 突变进行研究可能会发现 AD 的早期变化，并增强我们对整个生命周期中神经心理学功能的理解。本综述为从事 ADAD 研究和管理的研究人员、临床医生和政策制定者提供了有价值的见解。
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