Centre for Human Drug Research, Leiden, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands.
Centre for Human Drug Research, Leiden, the Netherlands; Leiden University Medical Center, Leiden, the Netherlands.
J Neurol Sci. 2023 Jun 15;449:120658. doi: 10.1016/j.jns.2023.120658. Epub 2023 Apr 12.
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.
随着年龄的增长，神经退行性疾病的患病率显著增加。神经退行性变是神经元功能逐渐丧失的过程，最终导致细胞死亡，进而导致认知功能障碍。因此，认知表现也可以被认为是与年龄相关的。本研究旨在探讨 NeuroCart 是否能在健康志愿者（HV）的药物敏感中枢神经系统测试中检测到与年龄相关的衰退，以及下降率和性别之间是否存在相互作用。本研究还调查了 NeuroCart 是否能够区分神经退行性疾病的疾病谱，与年龄匹配的 HV 相比，以及患者组是否存在与年龄相关的衰退。
这项回顾性研究包括了 2005 年至 2020 年间在 CHDR 进行的 93 项研究，这些研究都包含了 NeuroCart 测量结果，最终从 2729 名受试者中获得了数据。本分析包括了 5 项 NeuroCart 测试：平滑和扫视眼动、身体晃动、自适应跟踪、VVLT 和 N-back。数据来自 84 项健康男性和女性志愿者研究，年龄在 16 至 90 岁之间。9 项研究在阿尔茨海默病（AD）、帕金森病（PD）、亨廷顿病（HD）或血管性痴呆（VaD）患者中进行。使用回归分析方法对组间、性别、性别与年龄、组间与性别、组间与性别与年龄进行了分析。计算了每个组的平均年龄和组间每个年龄的平均年龄的最小二乘均值（LSM）和 95%置信区间（CI），并计算了每个性别的最小二乘均值（LSM）和 95%置信区间（CI）。
所有组的平均年龄和标准差（SD）为：HV 36.2 岁（19.3），68.3 CE 岁（8），PD 62.7 岁（8.5），HD 51.4 岁（9.8）和 VaD 66.9 岁（8.1）。HV 中所有 NeuroCart 测试的表现每年都显著下降。AD 与年龄匹配的 HV 相比，扫视峰值速度（SPV）增加（+26.28 度/秒，p=0.007），而 PD 和 HD 与年龄匹配的 HV 相比，SPV 下降（PD：-15.87 度/秒，p=0.038，HD：-22.52 度/秒，p=0.018）。HD 患者的 SPV 随年龄的增长下降速度快于 HV。在扫视峰值速度方面，HD 与 HV 之间的斜率存在显著差异，表明 HD 患者在该任务上的表现随年龄的增长下降速度快于 HV。平滑追踪显示出组间的总体显著差异（p=0.037。AD（-12.87%，p≤0.001）、PD（-4.45%，p≤0.001）和 VaD（-5.69%，p=0.005）的表现明显差于年龄匹配的 HV。身体晃动随年龄的增长而显著增加（p=0.021）。PD 和 HD 患者的姿势稳定性均较年龄匹配的 HV 下降（PD：+38.8%，p≤0.001，HD：154.9%，p≤0.001）。自适应跟踪随年龄的增长显著下降（p≤0.001）。AD（-7.54%，p≤0.001）、PD（-8.09%，p≤0.001）、HD（-5.19%，p≤0.001）和 VaD（-5.80%，p≤0.001）患者的自适应跟踪表现均较年龄匹配的 HV 下降。PD 患者与 HV 患者和 PD 患者与 HD 患者的自适应跟踪比较，差异有统计学意义，表明 PD 患者在该任务上的表现随年龄的增长下降速度快于 HV 和 HD。VVLT 延迟词回忆显示出组间的总体显著效应（p=0.006。AD（-5.83 个单词，p≤0.001）、HD（-3.40 个单词，p≤0.001）和 VaD（-5.51 个单词，p≤0.001）患者的正确延迟词回忆明显差于年龄匹配的 HV。
本研究表明，NeuroCart 能够检测 HV 中与年龄相关的认知表现下降，而不受性别影响。NeuroCart 能够检测 AD、PD、HD、VaD 和年龄匹配的 HV 之间的显著差异。疾病持续时间未知，因此本横断面研究无法显示疾病发作后的与年龄相关的衰退。本文表明，研究数字化神经认知测试对 HV 的影响具有重要意义。随着年龄的增长，认知表现会下降，这强调了在将 HV 纳入临床试验时需要考虑年龄因素。不同神经退行性疾病患者在 NeuroCart 任务上的表现模式存在差异，因此在 AD、PD、HD 和 VaD 患者中进行 NeuroCart 任务时应考虑到这一点。
