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. 2019 Mar 30;16(1):68.
doi: 10.1186/s12974-019-1454-z.

Balance between innate versus adaptive immune system and the risk of dementia: a population-based cohort study

Kimberly D van der Willik  1   2 , Lana Fani  1 , Dimitris Rizopoulos  3 , Silvan Licher  1 , Jesse Fest  4 , Sanne B Schagen  2   5 , M Kamran Ikram  1   6 , M Arfan Ikram  7
Affiliations

Balance between innate versus adaptive immune system and the risk of dementia: a population-based cohort study

Kimberly D van der Willik et al. J Neuroinflammation. .

Abstract

Background: Immunity has been suggested to be important in the pathogenesis of dementia. However, the contribution of innate versus adaptive immunity in the development of dementia is not clear. In this study, we aimed to investigate (1) the association between components of innate immunity (granulocytes and platelets) and adaptive immunity (lymphocytes) with risk of dementia and (2) the association between their derived ratios (granulocyte-to-lymphocyte ratio [GLR], platelet-to-lymphocyte ratio [PLR], and systemic immune-inflammation index [SII]), reflecting the balance between innate and adaptive immunity, with risk of dementia.

Methods: Blood cell counts were measured repeatedly between 2002 and 2015 in dementia-free participants of the prospective population-based Rotterdam Study. Participants were followed-up for dementia until 1 January 2016. Joint models were used to determine the association between granulocyte, platelets, and lymphocyte counts, and their derived ratios with risk of dementia.

Results: Of the 8313 participants (mean [standard deviation] age 61.1 [7.4] years, 56.9% women), 664 (8.0%) developed dementia during a median follow-up of 8.6 years. Doubling of granulocyte and platelet counts tended to be associated with an increased risk of dementia (HR [95%CI] 1.22 [0.89-1.67] and 1.45 [1.07-1.95], respectively). Doubling of the derived ratios GLR, PLR, and SII were all associated with an increased dementia risk (HR [95%CI] 1.26 [1.03-1.53], 1.27 [1.05-1.53], and 1.15 [0.98-1.34], respectively).

Conclusions: GLR, PLR, and SII are associated with an increased risk of dementia in the general population. This supports the role of an imbalance in the immune system towards innate immunity in the pathogenesis of dementia.

Keywords: Adaptive immune system; Alzheimer’s disease; Cohort studies; Dementia; Epidemiology; Innate immune system.

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Conflict of interest statement

Ethics approval and consent to participate

The Rotterdam Study was approved by the Medical Ethics Committee of Erasmus Medical Center and by the board of The Netherlands Ministry of Health, Welfare, and Sports. A written informed consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart participants for analysis association between blood cell counts, and their derived ratios, and dementia. Abbreviations: APOE, apolipoprotein E
Fig. 2
Fig. 2
Forest plots of the association of the GLR, PLR, and SII, and risk of dementia. Hazard ratios are shown in logarithmic scale with stratification by median age, sex, smoking status, diabetes mellitus, and APOE ε4 carrier status. Abbreviations: APOE, apolipoprotein E; GLR, granulocyte-to-lymphocyte ratio; n, number of incident dementia events; N, number of participants for analysis; PLR, platelet-to-lymphocyte ratio; SII, systemic immune-inflammation index
Fig. 3
Fig. 3
Forest plots of the association of granulocytes, platelets, and lymphocytes, and the risk of dementia. Hazard ratios are shown in logarithmic scale with stratification by median age, sex, smoking status, diabetes mellitus, and APOE ε4 carrier status. Abbreviations: APOE, apolipoprotein E; n, number of incident dementia events; N, number of participants for analysis
See this image and copyright information in PMC

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