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

Abstract

Introduction: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Alzheimer’s disease; Behavioral disturbances; Dementia; Leukocytosis; Parkinson’s disease.

Fig. 1.

Leukocytosis is the most prevalent pro-inflammatory WBC anomaly reported in AD and PD patients. Graph represents the total number of AD and PD patients registered in the 2016 and 2017 NIS and selected age-matched controls for the study. AD, Alzheimer’s disease; PD, Parkinson’s disease; WBCs, white blood cells; NIS, National Inpatient Sample.

Fig. 2.

Higher rates of leukocytosis are found in AD and PD patients with worsen neurocognitive decline. a Rates of MCI, dementia, and dementia + BPSD in AD. b Pro-inflammatory WBC anomalies in AD patients with MCI, dementia, and dementia + BPSD. c Rates of MCI and MND in PD patients. d Pro-inflammatory WBC anomalies in PD patients with normal cognition, MCI, and MND. e Rates of PDD andPDD + BPSD in PD patients with MND. f Pro-inflammatory WBC anomalies in PD patients with normal cognition, PDD, and PDD + BPSD. Graphs represent the percentage of AD and PD patients with WBC anomalies with respect to the total number of AD or PD patients registered in the 2016 and 2017 NIS database. Statistical analysis was carried out using the χ² test; * p < 0.05, ** p < 0.001. AD, Alzheimer’s disease; PD, Parkinson’s disease; WBCs, white blood cells; MCI, mild cognitive impairment; MND, major neurocognitive disorder; PDD, Parkinson’s disease dementia; BPSD, behavioral and psychological symptoms of dementia; NIS, National Inpatient Sample.

Fig. 3.

Leukocytosis is associated with higher odds of cognitive impairment and lower odds of BPSD in AD and PD patients with dementia. a Association of leukocytosis with risk of dementia + BPSD in AD patients. b Association of leukocytosis with risk of MND in PD patients. c Association of leukocytosis with risk of dementia in PD patients. d Association of leukocytosis with risk of PDD and BPSD. Graph values are based on the total number of AD and PD patients registered in the 2016 and 2017 NIS database. Logistic regression analyses show OR, and 95% CI, for unadjusted (crude) and adjusted (for demographics and comorbidities) leukocytosis contribution to neurocognitive features in AD and PD. AD, Alzheimer’s disease; PD, Parkinson’s disease; WBCs, white blood cells; MND, major neurocognitive disorder; PDD, Parkinson’s disease dementia; BPSD, behavioral and psychological symptoms of dementia; NIS, National Inpatient Sample; OR, odds ratio; CI, confidence interval.