Dataset Information

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

ABSTRACT:

Introduction

During menopause the level of estrogens is decreased, which may lead to cognitive impairment or dementia. Some forms of genetic polymorphism were found to be related to cognitive functions, including APOE and ESR1 (PvuII and XbaI) polymorphisms. In the present study we aimed to analyze the impact of interactions between APOE and ESR1 polymorphisms on cognitive functions in the group of postmenopausal women.

Material and methods

The study group consisted of 266 postmenopausal women aged 50-65 years without symptoms of dementia. A computerized battery of the Central Nervous System Vital Signs (CNS VS) test was used to diagnose cognitive functions. APOE and ESR1 polymorphisms were genotyped using multiplex PCR and PCR-RFLP methods, respectively. Statistical analysis was performed using two-way analysis of variance in Statistica software.

Results

The best memory, visual memory, processing and psychomotor speeds were found in women carrying the C allele of the PvuII polymorphism (TC + CC genotypes) in the presence of the APOE ?2/?3 genotype, while a lower outcome was noted in women with ?3/?3, and the lowest if they had the ?4 allele. In the case of women with TT genotype of the PvuII polymorphism, cognitive functioning did not decrease in women with the ?4 allele. A similar effect on cognitive functions was observed for AG + GG genotypes of the XbaI and APOE polymorphisms. Women who simultaneously carried CC PvuII and GG XbaI genotypes had the lowest cognitive functions.

Conclusions

Interactions of polymorphic variants of APOE and ESR1 genes influenced cognitive functions in postmenopausal women.

SUBMITTER: Pinkas J

PROVIDER: S-EPMC7811303 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Publications

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

Pinkas Jarosław J Bojar Iwona I Gujski Mariusz M Sarecka-Hujar Beata B Owoc Alfred A Raczkiewicz Dorota D

Archives of medical science : AMS 20181231 1

<h4>Introduction</h4>During menopause the level of estrogens is decreased, which may lead to cognitive impairment or dementia. Some forms of genetic polymorphism were found to be related to cognitive functions, including APOE and ESR1 (PvuII and XbaI) polymorphisms. In the present study we aimed to analyze the impact of interactions between APOE and ESR1 polymorphisms on cognitive functions in the group of postmenopausal women.<h4>Material and methods</h ...[more]

PMID: 33488853

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Project description:ObjectiveThis study investigated whether (1) cognitive functions change after the transition from the perimenopausal to the postmenopausal stage, (2) cognitive functions and walking are associated in middle-aged women, and (3) cognitive functions assessed in perimenopause are associated with walking after reaching the postmenopause or vice versa.MethodsIn total, 342 women, categorized as early (n = 158) or late perimenopausal (n = 184), were included in the study and followed up until postmenopausal. Psychomotor speed, executive functions related to set-shifting and updating, working memory, and visual memory were assessed. Walking was assessed with walking speed, walking distance, and dual-task cost in walking speed. Data was analyzed using the paired-samples t test, Wilcoxon signed rank test, multiple linear regression analysis, and structural equation modeling.ResultsWe found small but significant improvements in psychomotor speed (P = 0.01) and working memory (P < 0.001) among early perimenopausal and in psychomotor speed (P = 0.001), set-shifting (P = 0.02), visual memory (P = 0.002), and working memory (P < 0.001) among late perimenopausal women after the transition from peri- to postmenopause. Walking speed (β = 0.264, P = 0.001) and dual-task cost (β = 0.160, P = 0.03) were associated with updating, and walking distance was associated with updating and set-shifting (β = 0.198, P = 0.02, β=-0.178 P = 0.04 respectively) among the late perimenopausal women. We found no longitudinal associations between cognitive functions and walking.ConclusionCognitive performance remained unchanged or improved after reaching postmenopause. Cognitive functions and walking were associated during the late perimenopause, but the association depended on the cognitive process and nature of the physical task. Cognitive performance was not associated with walking after reaching postmenopause or vice versa.

Project description:ObjectiveAn Alzheimer's disease (AD) diagnosis is preceded by a long period of cognitive decline. We previously demonstrated increased risk of decline among individuals possessing one or more APOE ?4 alleles together with a family history of AD. The objective of this study is to investigate the possibility that such an increased risk might be due to AD risk genes with small effects in combination with APOE.MethodsParticipants in the Health and Retirement Study (HRS) over the age of 65, who contributed DNA, and had two or more evaluations with an abbreviated version of the modified Telephone Interview for Cognitive Status (TICS-m) were eligible for the study (n = 7451). A genetic risk score (g-score) was derived using AD risk genes' meta-analyses data, assigning risk according to the number of risk alleles and summed over all the risk genes. Trajectories of cognitive function were modeled in four groups of Caucasian participants with and without one or more APOE ?4 alleles and either a high or low g-score: APOE ?4-/low g-score; APOE ?4-/high g-score; APOE ?4+/low g-score; and APOE ?4+/high g-score. Post hoc analyses evaluated interactions between individual genes and APOE.ResultsIndividuals in the APOE ?4+/high g-score group exhibited the greatest cognitive decline over time (p<.0001). This risk appeared to be greater than the sum of the effects of either high g-score or APOE ?4 alone. When gene interactions were individually tested with APOE, a statistically significant interaction with CD33 was discovered (p = 0.04) although the interaction was no longer significant when adjusted for multiple comparisons.ConclusionsIndividuals with multiple AD risk genes in addition to having one or more APOE ?4 alleles are at greater risk of cognitive decline than individuals with either APOE ?4 or a high genetic risk score. Among those with one or more APOE ?4 alleles, having one or more copies of the CD33 C (risk) allele may further increase the risk of cognitive decline.

Dataset Information

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

Introduction

Material and methods

Results

Conclusions

Publications

Effect of interactions between <i>APOE</i> and <i>ESR1</i> polymorphisms on cognitive functions in postmenopausal women.

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