C-reactive protein as a predictor of mild cognitive impairment conversion into Alzheimer's disease dementia

Andreia Fernandes; Miguel Tábuas-Pereira; Diana Duro; Marisa Lima; Helena Gens; Beatriz Santiago; João Durães; Maria Rosário Almeida; Maria João Leitão; Inês Baldeiras; Isabel Santana

doi:10.1016/j.exger.2020.111004

C-reactive protein as a predictor of mild cognitive impairment conversion into Alzheimer's disease dementia

Exp Gerontol. 2020 Sep:138:111004. doi: 10.1016/j.exger.2020.111004. Epub 2020 Jun 16.

Affiliations

¹ Neurology Department, Centro Hospitalar e Universitário de Lisboa Central, Alameda de Santo António dos Capuchos, 1169-050 Lisboa, Portugal. Electronic address: 72688@chlc.min-saude.pt.
² Neurology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal.
³ Faculty of Psychology and Educational Sciences, University of Coimbra, R. Colégio Novo, 3000-115 Coimbra, Portugal.
⁴ Faculty of Medicine, University of Coimbra, R. Larga, 3004-504 Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
⁵ Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
⁶ Neurology Department, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075 Coimbra, Portugal; Faculty of Medicine, University of Coimbra, R. Larga, 3004-504 Coimbra, Portugal; Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.

PMID: 32561398
DOI: 10.1016/j.exger.2020.111004

Abstract

Background and aims: Increasing evidence suggests that inflammation plays an important role in brain aging and neurodegeneration. Pathological studies demonstrate the presence of C-reactive protein (CRP) in the senile plaques and neurofibrillary tangles in Alzheimer's disease (AD) brain tissue suggesting that CRP may play a role in its neuropathological processes. Some findings suggest that midlife elevations of serum CRP are a risk factor for AD. However, others found lower CRP levels in mild or moderate AD than in controls, suggesting that CRP levels could be different in different stages of disease. We aimed to assess the role of CRP as a predictor of Mild cognitive impairment (MCI) conversion into AD dementia.

Methods: We retrospectively reviewed the cohort of MCI patients followed at the Dementia Clinic, Neurology Department of University Hospital of Coimbra. We collected demographical, neuropsychological, genetic and laboratorial variables (including serum CRP measurements at the time of baseline laboratory tests). A Cox regression model was performed adjusted for the collected variables preconsidered to be predictors of dementia and the variable being studied (CRP) to assess for independent predictors of conversion.

Results: We included 130 patients, 58.5% female, with a mean age of onset of 65.5 ± 9.1 years and age at first assessment of 69.3 ± 8.5 years. The mean CRP was 0.33 ± 0.58 mg/dl. At follow-up (mean, 36.9 ± 27.0 months) 42.3% of MCI patients converted to dementia. Lower CSF Aβ42 (HR = 0.999, 95%CI = [0.997, 1.000], p = 0.015), lower MMSE score (HR = 0.864, 95%CI = [0.510, 1.595], p = 0.008) and lower CRP quartile (HR = 0.597, 95%CI = [0.435, 0.819], p = 0.001) were independent predictors of conversion.

Conclusion: CRP may add information of risk of conversion in MCI patients. Patients with lower CRP levels appear to have a more rapid conversion to AD dementia.

Keywords: Alzheimer; C-reactive protein; Conversion; Dementia; Inflammation; Mild cognitive impairment.

MeSH terms

Aged
Alzheimer Disease* / diagnosis
C-Reactive Protein
Cognitive Dysfunction* / diagnosis
Disease Progression
Female
Humans
Male
Middle Aged
Neuropsychological Tests
Retrospective Studies

Substances

C-Reactive Protein