Interaction between C-reactive protein and cognitive functions according to APOE gene polymorphism in post-menopausal women

Abstract

IntroductionA potential factor increasing the risk of the development of cognitive impairment with age is apolipoprotein E (APOE) ε4 carrier status. A subsequent factor which may increase the risk of development of cognitive impairment at an older age is the concentration of C-reactive protein (CRP). The objective of the study was to examine the relationship between cognitive functions and the concentration of CRP in post-menopausal women who were carriers of particular apolipoprotein E gene (APOE) polymorphisms.Material and methodsA group of 402 women was recruited to the study. The inclusion criteria were: minimum two years after the last menstruation, follicle-stimulating hormone (FSH) concentration 30 U/ml, no dementi signs on Montreal Cognitive Assessment (MoCA). The computerized battery of the Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. APOE genotyping was performed by multiplex PCR. The blood plasma CRP levels were determined. Statistical analysis was performed using Statistica software.ResultsThe level of neurocognitive index (NCI) and cognitive functions in post-menopausal women depends on apolipoprotein E gene polymorphism (p < 0.001) and the concentration of CRP (p < 0.05). A negative correlation was found between CRP and NCI (p = 0.018), and the reaction time (p = 0.008) of women with APOE ε2/ε3. A positive correlation was observed between CRP and visual memory (p = 0.025) in women with APOE ε3/ε3, and verbal memory (p = 0.023) in women with APOE ε3/ε4 or ε4/ε4.ConclusionsApolipoprotein E gene polymorphism may modify the relationship between CRP concentration and cognitive functions in post-menopausal women.

Apolipoprotein E genotype and the association between C‐reactive protein and postoperative delirium: Importance of gene‐protein interactions

“…Our findings further align with the growing literature that patients with more severe delirium are at highest risk for cognitive decline, 52 and it adds to the expanding knowledge of the complexity of gene functional networks, including gene-protein interactions. [53][54][55] Our results align with previous work on gene-protein interactions in delirium and AD. These findings (e.g., Ref.…”

“…found CRP to be the only mediator of this relationship after correction for multiple comparisons. Similarly, an APOE × CRP interaction has been reported for cognitive function among postmenopausal women and 4‐year decline in cognitive function in community‐dwelling older adults . Taken together, our finding of a gene‐protein interaction between APOE and CRP on postoperative delirium fit well with the studies of gene‐protein interactions on AD.…”

“…Our current findings suggest that some patients (APOE ε4 carriers) may be at greater risk for postoperative delirium under specific circumstances (high postoperative inflammation) than others (APOE non‐ε4 carriers), and these patients also experience delirium of greater duration and severity. Our findings further align with the growing literature that patients with more severe delirium are at highest risk for cognitive decline, and it adds to the expanding knowledge of the complexity of gene functional networks, including gene‐protein interactions …”

APOE – a genetic marker of comorbidity in subjects with morbid obesity

“…CRP has been associated with subsequent cognitive impairment and age-related cognitive decline, whereas the E4 allele, which was associated with low CRP, increases the risk of cognitive reduction and Alzheimer disease [ 5 , 6 , 41 , 42 ]. The interactions between CRP, the APOE genotype, cardiovascular diseases and cognitive functions and dementia are confusing and might depend on gender, age, and disease such as obesity [ 43 – 46 ]. The association between CRP and atherosclerosis might be diminished in subjects with obesity [ 44 ].…”

Effect of interactions between APOE and ESR1 polymorphisms on cognitive functions in postmenopausal women

“…Similarly, the presence of some depressive symptoms has a significant effect on cognitive impairment, which is increased in APOE ε4 carriers [ 29 ]. It was also demonstrated that in post-menopausal women the correlation between CRP level and cognitive functions may be modified by apolipoprotein E genotypes [ 30 ]. In addition, an enhanced negative effect of testosterone on cognition was found in postmenopausal women with at least one APOE ε4 allele [ 31 ].…”