The association of serum immunoglobulins with cognition and dementia: the Rotterdam Study

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Background Chronic inflammation is involved in the pathophysiology of dementia, but the association of serum immunoglobulins with dementia has been understudied and longitudinal data are currently lacking. We investigated the association of serum immunoglobulin (Ig) A, G, and M with cognition and dementia in a population-based cohort. Methods This study was embedded in the Rotterdam Study. Participants with information on serum immunoglobulin levels, measured between 1997 and 2009, were followed for incident dementia until 2016. Assessment of cognitive function and dementia was performed according to validated tests and clinical criteria respectively. We studied the association between serum immunoglobulins with prevalent and incident dementia using logistic regression and Cox proportional hazards regression analyses respectively. We performed linear regression analyses to quantify the cross-sectional association of serum immunoglobulins with global cognition as well as separate cognitive tests. Analyses were adjusted for age, sex, lifestyle, and cardiovascular factors. Results We included 8768 participants (median age of 62.2 years, 57% women, median follow-up 10.7 years). Overall, none of the immunoglobulins was associated with prevalent or incident dementia. Higher IgG levels were associated with lower scores of global cognition (adjusted standardized mean difference - 0.04; 95% confidence interval:- 0.06; - 0.02) and separate cognitive tests. Conclusion In middle-aged and older individuals from the general population, serum Igs were not associated with prevalent or incident dementia, which may imply that serum Igs are not involved in the pathophysiology of dementia. Although higher IgG levels were associated with worse cognitive function, studies with longitudinal data should exclude reverse causation.

Original languageEnglish
Pages (from-to)423-432
Number of pages10
JournalJournal of Neurology
Issue number1
Early online date19 Sept 2022
Publication statusPublished - Jan 2023

Bibliographical note

Funding Information:
This work was supported by Takeda [Grant Number IIR-NLD-002671 to V.A.S.H. Dalm]. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication. The Rotterdam Study is supported by the Erasmus MC University Medical Center and Erasmus University Rotterdam; The Netherlands Organisation for Scientific Research (NWO); The Netherlands Organisation for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); The Netherlands Genomics Initiative (NGI); the Ministry of Education, Culture and Science; the Ministry of Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. This study was partly performed as part of the Netherlands Consortium of Dementia Cohorts (NCDC), which receives funding in the context of Deltaplan Dementie from ZonMW Memorabel (projectnumber 73305095005) and Alzheimer Nederland. Further funding was obtained through the Stichting Erasmus Trustfonds, grant number 97030.2021.101.430/057/RB.

Publisher Copyright:
© 2022, The Author(s).


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