Vargas-Gonzalez Juan-Camilo, Chadha Antonella Santuccione, Castro-Aldrete Laura, Ferretti Maria Teresa, Tartaglia Carmela
University Health Network.
Women's Brain Project.
Res Sq. 2024 Mar 15:rs.3.rs-3982448. doi: 10.21203/rs.3.rs-3982448/v1.
The Clinical Dementia Rating Sum of Boxes (CDR-SB) is used to stage dementia severity; it is one of the most common outcome measurements in Alzheimer's Disease (AD) research and clinical trials. The CDR-SB requires an informant to provide input to stage a patient's dementia severity. The effect of the informant's characteristics on the CDR-SB is unknown. We aimed to evaluate the effect of the informant's sex, relationship to the patient, and frequency of contact on the CDR-SB scores in patients with Alzheimer's Disease with mild cognitive impairment or dementia included in the National Alzheimer's Coordinating Center Uniform Data Set (NACC-UDS).
We included all participants from the NACC-UDS that had AD as diagnosis, and information about the Mini-Mental State Examination or Montreal Cognitive Assessment scores, informant sex, relationship to patient and frequency of contact; we also analyzed the possible interaction between these characteristics on the CDR-SB as the outcome. We performed a multilevel linear regression analysis.
We included data from 20636 participants, totalling 47727 visits. Patients' age was 74.0 ± 9.4 years and 54.1% were females. Informant characteristics were mean age of 66.2 ± 13.2 years, 69.1% were females, and the relationship to patients was 60.5% spouse or partner, 26.7% children and 12.8% other relation. The CDR-SB scores were 0.20 higher (CI 95%: 0.11 to 0.29) when the informant was female. When comparing to informant's relationship with the baseline being spouse or partner, the CDR-SB was 0.39 higher (CI 95%: 0.25 to 0.53) when the informant was the patient's child and 0.18 lower (CI 95%: -0.35 to -0.01) if relationship was other. Regarding the frequency of contact, CDR-SB scores were 0.38 higher (CI95%: 0.28 to 0.47) when contact was at least once a week, 0.65 higher (CI95%: 0.52 to 0.78) when contact was daily, and 0.57 higher (CI95%: 0.46 to 0.69) when informant was living with the patient, baseline was a frequency of less than once per week. Finally, the interaction between informant relationships other and female patients showed a 0.24 higher CDR-SB score (CI95%: 0.03 to 0.46).
We found that the CDR-SB scores are significantly modified by informant characteristics and frequency of contact in the NACC-UDS patients with AD diagnosis. These findings hold clinical significance as informant characteristics ideally should not impact the staging of AD patients, and any such effects could introduce bias into clinical evaluations in clinical trials. Future research endeavours should investigate strategies to address and mitigate the influence of these confounding variables.
临床痴呆评定量表总盒分（CDR-SB）用于对痴呆严重程度进行分期；它是阿尔茨海默病（AD）研究和临床试验中最常用的结局指标之一。CDR-SB需要信息提供者提供信息以对患者的痴呆严重程度进行分期。信息提供者的特征对CDR-SB的影响尚不清楚。我们旨在评估信息提供者的性别、与患者的关系以及接触频率对纳入国家阿尔茨海默病协调中心统一数据集（NACC-UDS）的轻度认知障碍或痴呆的阿尔茨海默病患者CDR-SB评分的影响。
我们纳入了NACC-UDS中所有诊断为AD的参与者，以及关于简易精神状态检查或蒙特利尔认知评估评分、信息提供者性别、与患者的关系和接触频率的信息；我们还分析了这些特征之间可能对作为结局的CDR-SB产生的相互作用。我们进行了多水平线性回归分析。
我们纳入了20636名参与者的数据，共47727次就诊。患者年龄为74.0±9.4岁，54.1%为女性。信息提供者的特征为平均年龄66.2±13.2岁，69.1%为女性，与患者的关系为60.5%是配偶或伴侣，26.7%是子女，12.8%是其他关系。当信息提供者为女性时，CDR-SB评分高0.20（95%置信区间：0.11至0.29）。与信息提供者与基线为配偶或伴侣的关系相比，当信息提供者为患者的子女时，CDR-SB高0.39（95%置信区间：0.25至0.53），如果关系为其他，则低0.18（95%置信区间：-0.35至-0.01）。关于接触频率，当每周至少接触一次时，CDR-SB评分高0.38（95%置信区间：0.28至0.47），每天接触时高0.65（95%置信区间：0.52至0.78），当信息提供者与患者同住时高0.57（95%置信区间：0.46至0.69），基线是每周接触少于一次。最后，信息提供者关系为其他且为女性患者之间的相互作用显示CDR-SB评分高0.24（95%置信区间：0.03至0.46）。
我们发现，在NACC-UDS中诊断为AD的患者中，信息提供者的特征和接触频率会显著改变CDR-SB评分。这些发现具有临床意义，因为理想情况下信息提供者的特征不应影响AD患者的分期，而任何此类影响都可能在临床试验的临床评估中引入偏差。未来的研究应探索解决和减轻这些混杂变量影响的策略。
