Veterans Affairs Connecticut Healthcare System, Clinical Neurosciences Division, US Department of Veterans Affairs, West Haven2Department of Psychiatry, Yale School of Medicine, New Haven, Connecticut.
The Florey Institute of Neuroscience and Mental Health, The University of Melbourne, Parkville, Victoria, Australia4Department of Neurology, Warren Alpert School of Medicine, Brown University, Providence, Rhode Island.
JAMA Psychiatry. 2015 Mar;72(3):284-91. doi: 10.1001/jamapsychiatry.2014.2476.
Alzheimer disease (AD) is now known to have a long preclinical phase in which pathophysiologic processes develop many years, even decades, before the onset of clinical symptoms. Although the presence of abnormal levels of amyloid-β (Aβ) is associated with higher rates of progression to clinically classified mild cognitive impairment or dementia, little research has evaluated potentially modifiable moderators of Aβ-related cognitive decline, such as anxiety and depressive symptoms.
To evaluate the association between Aβ status and cognitive changes, and the role of anxiety and depressive symptoms in moderating Aβ-related cognitive changes in the preclinical phase of AD.
DESIGN, SETTING, AND PARTICIPANTS: In this multicenter, prospective cohort study with baseline and 18-, 36-, and 54-month follow-up assessments, we studied 333 healthy, older adults at hospital-based research clinics.
Carbon 11-labeled Pittsburgh Compound B (PiB)-, florbetapir F 18-, or flutemetamol F 18-derived measures of Aβ, Hospital Anxiety and Depression Scale scores, and comprehensive neuropsychological evaluation that yielded measures of global cognition, verbal memory, visual memory, attention, language, executive function, and visuospatial ability.
A positive Aβ (Aβ+) status at baseline was associated with a significant decline in global cognition, verbal memory, language, and executive function, and elevated anxiety symptoms moderated these associations. Compared with the Aβ+, low-anxiety group, slopes of cognitive decline were significantly more pronounced in the Aβ+, high-anxiety group, with Cohen d values of 0.78 (95% CI, 0.33-1.23) for global cognition, 0.54 (95% CI, 0.10-0.98) for verbal memory, 0.51 (95% CI, 0.07-0.96) for language, and 0.39 (95% CI, 0.05-0.83) for executive function. These effects were independent of age, educational level, IQ, APOE genotype, subjective memory complaints, vascular risk factors, and depressive symptoms; furthermore, depressive symptoms and subjective memory complaints did not moderate the association between Aβ and cognitive decline.
These results provide additional support for the deleterious effect of elevated Aβ levels on cognitive function in preclinical AD. They further suggest that elevated anxiety symptoms moderate the effect of Aβ on cognitive decline in preclinical AD, resulting in more rapid decline in several cognitive domains. Given that there is currently no standard antiamyloid therapy and that anxiety symptoms are amenable to treatment, these findings may help inform risk stratification and management of the preclinical phase of AD.
阿尔茨海默病（AD）现在被认为有一个很长的临床前阶段，在此期间，病理生理过程在出现临床症状之前会发展多年，甚至几十年。尽管异常水平的淀粉样蛋白-β（Aβ）与更高的进展到临床分类为轻度认知障碍或痴呆的比率有关，但很少有研究评估 Aβ 相关认知衰退的潜在可调节调节剂，如焦虑和抑郁症状。
评估 Aβ 状态与认知变化之间的关系，以及焦虑和抑郁症状在调节 AD 临床前阶段 Aβ 相关认知变化中的作用。
设计、地点和参与者：在这项多中心、前瞻性队列研究中，我们在基线和 18、36 和 54 个月的随访评估中，研究了 333 名在医院研究诊所的健康老年成年人。
用碳 11 标记的匹兹堡化合物 B（PiB）、氟贝他吡 F 18 或氟曲美特 F 18 衍生的 Aβ 测量、医院焦虑和抑郁量表评分以及全面的神经心理学评估，得出了总体认知、言语记忆、视觉记忆、注意力、语言、执行功能和视空间能力的测量值。
基线时的阳性 Aβ（Aβ+）状态与整体认知、言语记忆、语言和执行功能的显著下降有关，而焦虑症状的升高则调节了这些关联。与 Aβ+、低焦虑组相比，Aβ+、高焦虑组的认知下降斜率明显更为明显，Cohen d 值分别为 0.78（95%CI，0.33-1.23）用于整体认知，0.54（95%CI，0.10-0.98）用于言语记忆，0.51（95%CI，0.07-0.96）用于语言，以及 0.39（95%CI，0.05-0.83）用于执行功能。这些影响独立于年龄、教育水平、智商、APOE 基因型、主观记忆主诉、血管危险因素和抑郁症状；此外，抑郁症状和主观记忆主诉并不调节 Aβ 与认知下降之间的关系。
这些结果为 Aβ 水平升高对 AD 临床前认知功能的有害影响提供了额外的支持。它们进一步表明，升高的焦虑症状调节了 Aβ 对 AD 临床前认知下降的影响，导致几个认知领域的下降速度更快。鉴于目前尚无标准的抗淀粉样蛋白治疗方法，且焦虑症状可治疗，这些发现可能有助于告知 AD 临床前阶段的风险分层和管理。
