Abstract：
The prevalence of neurodegenerative diseases increases significantly with increasing age. Neurodegeneration is the progressive loss of function of neurons that eventually leads to cell death, which in turn leads to cognitive disfunction. Cognitive performance can therefore also be considered age dependent. The current study investigated if the NeuroCart can detect age related decline on drug-sensitive CNS-tests in healthy volunteers (HV), and whether there are interactions between the rates of decline and sex. This study also investigated if the NeuroCart was able to differentiate disease profiles of neurodegenerative diseases, compared to age-matched HV and if there is age related decline in patient groups.
This retrospective study encompassed 93 studies, performed at CHDR between 2005 and 2020 that included NeuroCart measurements, which resulted in data from 2729 subjects. Five NeuroCart tests were included in this analysis: smooth and saccadic eye movements, body sway, adaptive tracking, VVLT and N-back. Data from 84 healthy male and female volunteer studies, aged 16-90, were included. Nine studies were performed in patients with Alzheimer\'s disease (AD), Parkinson\'s disease (PD), Huntington\'s disease (HD) or vascular dementia (VaD). The data were analyzed with regression analyses on age by group, sex, sex by age, group by sex and group by sex by age. Least square means (LSMs) and 95% confidence intervals (CIs) were calculated for each group at the average age of the group, and at the average age of each of the other groups, and per sex.
Mean age and standard deviation (SD) for all groups was: HV 36.2 years (19.3), 68.3 CE years (8), PD 62.7 years (8.5), HD 51.4 years (9.8) and VaD 66.9 years (8.1). Performance on all NeuroCart tests decreased significantly each year in HV. Saccadic peak velocity (SPV) was increased in AD compared to age-matched HV (+26.28 degrees/s, p = 0.007), while SPV was decreased for PD and HD compared to age-matched HV (PD: -15.87 degrees/s, p = 0.038, HD: -22.52 degrees/s, p = 0.018). In HD patients SPV decreased faster with age compared to HV. On saccadic peak velocity the slopes between HD vs HV were significantly different, indicating a faster decline in performance on this task for HD patients compared to HV per age year. Smooth pursuit showed an overall significant difference between subject groups (p = 0.037. Significantly worse performance was found for AD (-12.87%, p ≤0.001), PD (-4.45%, p ≤0.001) and VaD (-5.69%, p = 0.005) compared to age-matched HV. Body sway significantly increased with age (p = 0.021). Postural stability was decreased for both PD and HD compared to age-matched HV (PD: +38.8%, p ≤0.001, HD: 154.9%, p ≤0.001). The adaptive tracking was significantly decreased with age (p ≤0.001). Adaptive tracking performance by AD (-7.54%, p ≤0.001), PD (-8.09%, p ≤0.001), HD (-5.19%, p ≤0.001) and VaD (-5.80%, p ≤0.001) was decreased compared to age-matched HV. Adaptive tracking in PD patients vs HV and in PD vs HD patients was significantly different, indicating a faster decline on this task per age year for PD patients compared to HV and HD. The VVLT delayed word recall showed an overall significant effect of subject group (p = 0.006. Correct delayed word recall was decreased for AD (-5.83 words, p ≤0.001), HD (-3.40 words, p ≤0.001) and VaD (-5.51 words, p ≤0.001) compared to age-matched HV.
This study showed that the NeuroCart can detect age-related decreases in performance in HV, which were not affected by sex. The NeuroCart was able to detect significant differences in performance between AD, PD, HD, VaD and age-matched HV. Disease durations were unknown, therefore this cross-sectional study was not able to show age-related decline after disease onset. This article shows the importance of investigating age-related decline on digitalized neurocognitive test batteries. Performance declines with age, which emphasizes the need to correct for age when including HV in clinical trials. Patients with different neurogenerative diseases have distinct performance patterns on the NeuroCart, which this should be considered when performing NeuroCart tasks in patients with AD, PD, HD and VaD.
This retrospective study encompassed 93 studies, performed at CHDR between 2005 and 2020 that included NeuroCart measurements, which resulted in data from 2729 subjects. Five NeuroCart tests were included in this analysis: smooth and saccadic eye movements, body sway, adaptive tracking, VVLT and N-back. Data from 84 healthy male and female volunteer studies, aged 16-90, were included. Nine studies were performed in patients with Alzheimer\'s disease (AD), Parkinson\'s disease (PD), Huntington\'s disease (HD) or vascular dementia (VaD). The data were analyzed with regression analyses on age by group, sex, sex by age, group by sex and group by sex by age. Least square means (LSMs) and 95% confidence intervals (CIs) were calculated for each group at the average age of the group, and at the average age of each of the other groups, and per sex.
Mean age and standard deviation (SD) for all groups was: HV 36.2 years (19.3), 68.3 CE years (8), PD 62.7 years (8.5), HD 51.4 years (9.8) and VaD 66.9 years (8.1). Performance on all NeuroCart tests decreased significantly each year in HV. Saccadic peak velocity (SPV) was increased in AD compared to age-matched HV (+26.28 degrees/s, p = 0.007), while SPV was decreased for PD and HD compared to age-matched HV (PD: -15.87 degrees/s, p = 0.038, HD: -22.52 degrees/s, p = 0.018). In HD patients SPV decreased faster with age compared to HV. On saccadic peak velocity the slopes between HD vs HV were significantly different, indicating a faster decline in performance on this task for HD patients compared to HV per age year. Smooth pursuit showed an overall significant difference between subject groups (p = 0.037. Significantly worse performance was found for AD (-12.87%, p ≤0.001), PD (-4.45%, p ≤0.001) and VaD (-5.69%, p = 0.005) compared to age-matched HV. Body sway significantly increased with age (p = 0.021). Postural stability was decreased for both PD and HD compared to age-matched HV (PD: +38.8%, p ≤0.001, HD: 154.9%, p ≤0.001). The adaptive tracking was significantly decreased with age (p ≤0.001). Adaptive tracking performance by AD (-7.54%, p ≤0.001), PD (-8.09%, p ≤0.001), HD (-5.19%, p ≤0.001) and VaD (-5.80%, p ≤0.001) was decreased compared to age-matched HV. Adaptive tracking in PD patients vs HV and in PD vs HD patients was significantly different, indicating a faster decline on this task per age year for PD patients compared to HV and HD. The VVLT delayed word recall showed an overall significant effect of subject group (p = 0.006. Correct delayed word recall was decreased for AD (-5.83 words, p ≤0.001), HD (-3.40 words, p ≤0.001) and VaD (-5.51 words, p ≤0.001) compared to age-matched HV.
This study showed that the NeuroCart can detect age-related decreases in performance in HV, which were not affected by sex. The NeuroCart was able to detect significant differences in performance between AD, PD, HD, VaD and age-matched HV. Disease durations were unknown, therefore this cross-sectional study was not able to show age-related decline after disease onset. This article shows the importance of investigating age-related decline on digitalized neurocognitive test batteries. Performance declines with age, which emphasizes the need to correct for age when including HV in clinical trials. Patients with different neurogenerative diseases have distinct performance patterns on the NeuroCart, which this should be considered when performing NeuroCart tasks in patients with AD, PD, HD and VaD.
摘要：
背景：随着年龄的增长，神经退行性疾病的患病率显着增加。神经变性是神经元功能的进行性丧失，最终导致细胞死亡，进而导致认知障碍。因此，认知表现也可以被认为是年龄依赖性的。当前的研究调查了NeuroCart是否可以在健康志愿者（HV）的药物敏感性CNS测试中检测到与年龄相关的下降，以及下降率和性别之间是否存在相互作用。这项研究还调查了NeuroCart是否能够区分神经退行性疾病的疾病特征，与年龄匹配的HV相比，如果患者组存在年龄相关的下降。
方法：这项回顾性研究包括93项研究，在2005年至2020年期间在CHDR进行，包括NeuroCart测量，这产生了2729名受试者的数据。这项分析包括五项NeuroCart测试：平滑和扫视的眼球运动，身体摇摆，自适应跟踪,VVLT和N-back。来自84个健康男性和女性志愿者研究的数据，年龄16-90岁，包括在内。九项研究在阿尔茨海默病（AD）患者中进行，帕金森病（PD），亨廷顿病（HD）或血管性痴呆（VaD）。对数据进行了分组年龄回归分析，性别,按年龄划分的性别，按性别分组，按年龄按性别分组。计算各组平均年龄的最小二乘均值(LSM)和95%置信区间(CIs),在其他各组的平均年龄上，和每个性别。
结果：所有组的平均年龄和标准偏差（SD）为：HV36.2岁（19.3），68.3CE年（8），PD62.7年（8.5年），HD51.4年（9.8年）和VaD66.9年（8.1年）。在HV中，所有NeuroCart测试的性能每年都显着下降。与年龄匹配的HV（+26.28度/秒，p=0.007),而与年龄匹配的HV相比，PD和HD的SPV降低（PD：-15.87度/秒，p=0.038,HD:-22.52度/秒,p=0.018)。在HD患者中，与HV相比，SPV随年龄下降更快。在扫视峰值速度上，HD与HV之间的斜率显着不同，表明与每个年龄的HV相比，HD患者在这项任务上的表现下降更快。平稳追踪显示受试者组之间的总体显着差异（p=0.037。发现AD的表现明显更差（-12.87％，p≤0.001)，PD（-4.45%，p≤0.001)和VaD(-5.69%，p=0.005）与年龄匹配的HV相比。随着年龄的增长，身体摇摆显著增加（p=0.021）。与年龄匹配的HV相比，PD和HD的姿势稳定性均降低（PD：38.8％，p≤0.001,HD:154.9%,p≤0.001)。自适应跟踪随着年龄的增长而显著下降(p≤0.001)。AD的自适应跟踪性能(-7.54%，p≤0.001)，PD（-8.09%，p≤0.001)，高清（-5.19%，p≤0.001)和VaD(-5.80%，与年龄匹配的HV相比，p≤0.001）降低。PD患者vsHV和PD患者vsHD患者的自适应跟踪有显著差异，表明与HV和HD相比，PD患者每个年龄段的任务下降更快。VVLT延迟单词回忆显示出受试者组的总体显着影响（p=0.006。正确的延迟单词回忆减少了AD（-5.83单词，p≤0.001)，HD(-3.40字,p≤0.001)和VaD(-5.51字，p≤0.001)与年龄匹配的HV相比。
结论：这项研究表明，NeuroCart可以检测到与年龄相关的HV表现下降，不受性别影响。NeuroCart能够检测到AD之间表现的显著差异，PD,HD,VaD和年龄匹配的HV。疾病持续时间未知，因此,这项横断面研究未能显示疾病发病后年龄相关的下降.本文显示了调查数字化神经认知测试电池与年龄相关的下降的重要性。性能随着年龄的增长而下降，这强调了在临床试验中包括HV时需要校正年龄。不同神经退行性疾病的患者在NeuroCart上有不同的表现模式,在AD患者中执行NeuroCart任务时应考虑这一点，PD,HD和VaD。
方法：这项回顾性研究包括93项研究，在2005年至2020年期间在CHDR进行，包括NeuroCart测量，这产生了2729名受试者的数据。这项分析包括五项NeuroCart测试：平滑和扫视的眼球运动，身体摇摆，自适应跟踪,VVLT和N-back。来自84个健康男性和女性志愿者研究的数据，年龄16-90岁，包括在内。九项研究在阿尔茨海默病（AD）患者中进行，帕金森病（PD），亨廷顿病（HD）或血管性痴呆（VaD）。对数据进行了分组年龄回归分析，性别,按年龄划分的性别，按性别分组，按年龄按性别分组。计算各组平均年龄的最小二乘均值(LSM)和95%置信区间(CIs),在其他各组的平均年龄上，和每个性别。
结果：所有组的平均年龄和标准偏差（SD）为：HV36.2岁（19.3），68.3CE年（8），PD62.7年（8.5年），HD51.4年（9.8年）和VaD66.9年（8.1年）。在HV中，所有NeuroCart测试的性能每年都显着下降。与年龄匹配的HV（+26.28度/秒，p=0.007),而与年龄匹配的HV相比，PD和HD的SPV降低（PD：-15.87度/秒，p=0.038,HD:-22.52度/秒,p=0.018)。在HD患者中，与HV相比，SPV随年龄下降更快。在扫视峰值速度上，HD与HV之间的斜率显着不同，表明与每个年龄的HV相比，HD患者在这项任务上的表现下降更快。平稳追踪显示受试者组之间的总体显着差异（p=0.037。发现AD的表现明显更差（-12.87％，p≤0.001)，PD（-4.45%，p≤0.001)和VaD(-5.69%，p=0.005）与年龄匹配的HV相比。随着年龄的增长，身体摇摆显著增加（p=0.021）。与年龄匹配的HV相比，PD和HD的姿势稳定性均降低（PD：38.8％，p≤0.001,HD:154.9%,p≤0.001)。自适应跟踪随着年龄的增长而显著下降(p≤0.001)。AD的自适应跟踪性能(-7.54%，p≤0.001)，PD（-8.09%，p≤0.001)，高清（-5.19%，p≤0.001)和VaD(-5.80%，与年龄匹配的HV相比，p≤0.001）降低。PD患者vsHV和PD患者vsHD患者的自适应跟踪有显著差异，表明与HV和HD相比，PD患者每个年龄段的任务下降更快。VVLT延迟单词回忆显示出受试者组的总体显着影响（p=0.006。正确的延迟单词回忆减少了AD（-5.83单词，p≤0.001)，HD(-3.40字,p≤0.001)和VaD(-5.51字，p≤0.001)与年龄匹配的HV相比。
结论：这项研究表明，NeuroCart可以检测到与年龄相关的HV表现下降，不受性别影响。NeuroCart能够检测到AD之间表现的显著差异，PD,HD,VaD和年龄匹配的HV。疾病持续时间未知，因此,这项横断面研究未能显示疾病发病后年龄相关的下降.本文显示了调查数字化神经认知测试电池与年龄相关的下降的重要性。性能随着年龄的增长而下降，这强调了在临床试验中包括HV时需要校正年龄。不同神经退行性疾病的患者在NeuroCart上有不同的表现模式,在AD患者中执行NeuroCart任务时应考虑这一点，PD,HD和VaD。
