C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population

Sharif H Hegazy; Jesper Qvist Thomassen; Ida Juul Rasmussen; Børge G Nordestgaard; Anne Tybjaerg-Hansen; Ruth Frikke-Schmidt

doi:10.1002/alz.12568

C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population

Sharif H Hegazy, Jesper Qvist Thomassen, Ida Juul Rasmussen, Børge G Nordestgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt^*

^*Corresponding author for this work

27 Citations (Scopus)

Abstract

INTRODUCTION: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear.

METHODS: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined.

RESULTS: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29-2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m2 (P = 4 × 10-6 ).

DISCUSSION: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.

Original language	English
Journal	Alzheimer's & dementia : the journal of the Alzheimer's Association
Volume	18
Issue number	11
Pages (from-to)	2262-2271
Number of pages	10
ISSN	1552-5260
DOIs	https://doi.org/10.1002/alz.12568
Publication status	Published - Nov 2022

Keywords

Alzheimer Disease/epidemiology
Body Mass Index
C-Reactive Protein/analysis
Humans
Proportional Hazards Models
Prospective Studies
Risk Factors
CRP
C-reactive protein
body mass index
gene–environment interaction
Alzheimer's disease

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10.1002/alz.12568

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Hegazy, S. H., Thomassen, J. Q., Rasmussen, I. J., Nordestgaard, B. G., Tybjaerg-Hansen, A., & Frikke-Schmidt, R. (2022). C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population. Alzheimer's & dementia : the journal of the Alzheimer's Association, 18(11), 2262-2271. https://doi.org/10.1002/alz.12568

C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population. / Hegazy, Sharif H; Thomassen, Jesper Qvist; Rasmussen, Ida Juul et al.
In: Alzheimer's & dementia : the journal of the Alzheimer's Association, Vol. 18, No. 11, 11.2022, p. 2262-2271.

Research output: Contribution to journal › Journal article › Research › peer-review

Hegazy, SH, Thomassen, JQ, Rasmussen, IJ, Nordestgaard, BG , Tybjaerg-Hansen, A & Frikke-Schmidt, R 2022, 'C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population', Alzheimer's & dementia : the journal of the Alzheimer's Association, vol. 18, no. 11, pp. 2262-2271. https://doi.org/10.1002/alz.12568

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abstract = "INTRODUCTION: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear.METHODS: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined.RESULTS: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29-2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m2 (P = 4 × 10-6 ).DISCUSSION: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.",

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AU - Frikke-Schmidt, Ruth

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N2 - INTRODUCTION: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear.METHODS: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined.RESULTS: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29-2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m2 (P = 4 × 10-6 ).DISCUSSION: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.

AB - INTRODUCTION: Increased plasma levels of C-reactive protein (CRP) in midlife are associated with increased risk of Alzheimer's disease (AD), whereas in older age the opposite association is observed. Whether genetically determined CRP is associated with AD remains unclear.METHODS: A total of 111,242 White individuals from the Copenhagen General Population Study and the Copenhagen City Heart Study were included. Plasma levels of CRP and four regulatory genetic variants in the CRP gene were determined.RESULTS: For CRP percentile group 1 to 5 (lowest plasma CRP) versus the 50 to 75 group (reference), the hazard ratio for AD was 1.69 (95% confidence interval 1.29-2.16). Genetically low CRP was associated with increased risk of AD in individuals with body mass index ≤25 kg/m2 (P = 4 × 10-6 ).DISCUSSION: Low plasma levels of CRP at baseline were associated with high risk of AD in individuals from the general population. These observational findings were supported by genetic studies.

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C-reactive protein levels and risk of dementia-Observational and genetic studies of 111,242 individuals from the general population

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