Supplementary Material for: Peripheral Leukocytosis Predicts Cognitive Decline but Not Behavioral Disturbances: A Nationwide Study of Alzheimer’s and Parkinson’s Disease Patients

<b><i>Introduction:</i></b> Peripheral and central nervous system inflammation have been linked to the classic symptoms of Parkinson’s disease (PD) and Alzheimer’s disease (AD). However, it remains unclear whether the analysis of routine systemic inflammatory markers could represent a useful prediction tool to identify clinical subtypes in patients with Parkinson’s and Alzheimer’s at higher risk of dementia-associated symptoms, such as behavioral and psychological symptoms of dementia (BPSD). <b><i>Methods:</i></b> We performed a multivariate logistic regression using the 2016 and 2017 National Inpatient Sample with International Classification of Diseases 10th edition codes to assess if pro-inflammatory white blood cells (WBCs) anomalies correlate with dementia and BPSD in patients with these disorders. <b><i>Results:</i></b> We found that leukocytosis was the most common WBC inflammatory marker identified in 3.9% of Alzheimer’s and 3.3% Parkinson’s patients. Leukocytosis was also found to be an independent risk factor for Parkinson’s dementia. Multivariate analysis of both cohorts showed that leukocytosis is significantly decreased in patients with BPSD compared to patients without BPSD. <b><i>Conclusions:</i></b> These results suggest a link between leukocytosis and the pathophysiology of cognitive dysfunction in both PD and AD. A better understanding of the role of systemic neuroinflammation on these devastating neurodegenerative disorders may facilitate the development of cost-effective blood biomarkers for patient’s early diagnosis and more accurate prognosis.

<b><i>引言：</i></b> 外周及中枢神经系统炎症与帕金森病（PD）、阿尔茨海默病（AD）的典型症状密切相关。然而，常规全身炎症标志物分析能否作为有效预测工具，用以识别痴呆相关症状（如痴呆行为与精神症状（BPSD））风险更高的帕金森病及阿尔茨海默病患者的临床亚型，目前仍不明确。<b><i>方法：</i></b> 本研究借助2016年与2017年全国住院患者样本，结合国际疾病分类第10版（ICD-10）编码开展多因素logistic回归分析，以评估促炎性白细胞（WBCs）异常是否与上述疾病患者的痴呆及BPSD存在关联。<b><i>结果：</i></b> 本研究发现，白细胞增多症是最常见的白细胞炎性标志物，在3.9%的阿尔茨海默病患者与3.3%的帕金森病患者中检出。此外，白细胞增多症被证实为帕金森病痴呆的独立危险因素。两项队列的多因素分析显示，相较于无BPSD的患者，合并BPSD的患者白细胞增多症发生率显著降低。<b><i>结论：</i></b> 上述结果表明，白细胞增多症与PD及AD患者认知功能障碍的病理生理机制存在关联。深入阐明全身神经炎症在这两类危害性极大的神经退行性疾病中的作用，或有助于开发兼具成本效益的血液生物标志物，用于患者的早期诊断与更精准的预后评估。