To explore the trajectories and the change-points of global and five domain-specific cognitive functions before the onset of Alzheimer's disease (AD). Data was retrieved from the Alzheimer's Disease Neuroimaging Initiative with follow-up from 2005 to 2022. Participants with mild cognitive impairment (MCI) at baseline and those who progressed to AD during follow-up were included. The time of AD onset was defined as the visit time when participant was first diagnosed as AD during follow-up. Global and five domain-specific cognitive functions (immediate memory, visuospatial ability, language, processing speed and executive function) were assessed by Mini-Mental State Examination, Immediate recalling trials of Rey Auditory Verbal Learning Test, Clock Drawing Test, Animal Fluency Test, Part A and B of Trail Making Test, respectively. Their trajectories and change-points before AD onset were explored by generalized additive mixed models and piecewise linear regression models, respectively. 349 participants were diagnosed as MCI at baseline and converted to AD during follow-up, who were included in this study. They had been visited on an average of 4.6 times (SD = 2.1, range = 2.0–13.0), with a total of 1593 visits. Their mean baseline age and AD onset age were 74.4 (SD = 6.4, range = 60.0–88.4) and 77.0 (SD = 6.8, range = 60.5–94.7) years, respectively. Baseline age and educational year were significantly associated with global cognitive, immediate memory, language and executive function. Men presented better global cognitive function ( = 0.54, < 0.05) but poorer immediate memory ( = −1.72, < 0.05) than women. Immediate memory and visuospatial ability showed the earliest change-points at 4 years before the onset of AD (Note as -4years), followed by language (-3.5years), executive function (-2.5 years), processing speed (-2.0 years), and finally the global cognitive function (-1.5years). The trajectories of the six neuropsychological scores were non-linear and showed deterioration in functions over time. Immediate memory and visuospatial ability showed the earliest change-points prior to AD onset.

中文翻译：

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轻度认知障碍患者 AD 发病前不同领域认知能力下降的轨迹

探讨阿尔茨海默病（AD）发病前整体认知功能和五个特定领域认知功能的轨迹和变化点。数据取自阿尔茨海默病神经影像计划，并进行了 2005 年至 2022 年的随访。基线时患有轻度认知障碍 (MCI) 的参与者以及在随访期间进展为 AD 的参与者均被纳入其中。AD发病时间定义为随访期间参与者首次被诊断为AD时的就诊时间。通过简易精神状态检查、雷伊听觉言语学习测试的立即回忆试验、时钟绘图测试、动物流畅性测试、分别是轨迹制作测试的 A 部分和 B 部分。分别通过广义加性混合模型和分段线性回归模型探索了 AD 发病前的轨迹和变化点。349 名参与者在基线时被诊断为 MCI，并在随访期间转变为 AD，他们被纳入本研究。他们平均被访问 4.6 次（SD = 2.1，范围 = 2.0–13.0），总共 1593 次访问。他们的平均基线年龄和 AD 发病年龄分别为 74.4（SD = 6.4，范围 = 60.0–88.4）和 77.0（SD = 6.8，范围 = 60.5–94.7）岁。基线年龄和受教育年数与整体认知、即时记忆、语言和执行功能显着相关。与女性相比，男性的整体认知功能更好（= 0.54，< 0.05），但即时记忆能力较差（= −1.72，< 0.05）。即刻记忆和视觉空间能力最早出现变化点为AD发病前4年（注为-4年），其次是语言（-3.5年）、执行功能（-2.5年）、处理速度（-2.0年） ，最后是全局认知功能（-1.5 年）。六项神经心理学评分的轨迹是非线性的，并且随着时间的推移，功能逐渐恶化。即时记忆和视觉空间能力显示出 AD 发病前最早的变化点。