APOE ε4 Allele Modulates The Differential Effects of Education on Cognition in Alzheimer’s Continuum: The SILCODE Study

Abstract Background: Elders with subjective cognitive decline (SCD) in the absence of objective cognitive impairment are at increased risk of developing mild cognitive impairment (MCI) or Alzheimer’s disease (AD). Previous study has reported that higher education was associated with better performance in cognitive performance in elderly people with SCD. However, it is not clear whether there is a differential effect of education on cognition between healthy controls (HC), individuals with SCD and patients with cognitive impairment (CI).Methods: We performed a cross-sectional study that included 186 HC, 279 SCD subjects and 79 patients with CI from the Sino Longitudinal Study on Cognitive Decline (SILCODE) project. A series of neuropsychological tests of memory, executive, language, and general cognitive function were used to assess the subjects cognitive performance. We performed multiple linear regression models to examine the effect of education on neuropsychological test scores in the total sample and then described differences in the effect according to three different groups. In addition, we presented the effect of education on total test score expressed as a global composite z-scores in the total sample and three different groups, respectively. Furthermore, we examined whether apolipoprotein E ε4 allele (APOE ε4) status would regulate the effect of education on the global composite score among three different groups.Results: Education has a positive effect on cognition in the total sample. Stratification for different groups showed that the positive effect of education on cognition is found in HC and SCD group, while education has a negative effect on cognition in the CI group. Furthermore, we found the APOE ε4 allele does not modify the positive effect of education on cognition in the HC group, but the APOE ε4 allele weaken that beneficial effect in the SCD group and maintain the negative effect in the CI group.Conclusions: High education may delay the progression from SCD to cognitive impairment and yield differential effects on cognition across the spectrum of AD. Furthermore, that differential effects are subjected to modulation by the APOE ε4 status.

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Memory in individuals with mild cognitive impairment in relation to APOE and CSF Aβ42

International Psychogeriatrics ◽

10.1017/s1041610210000335 ◽

2010 ◽

Vol 22 (4) ◽

pp. 598-606 ◽

Cited By ~ 5

Author(s):

Valgeir Thorvaldsson ◽

Arto Nordlund ◽

Ivar Reinvang ◽

Kaj Blennow ◽

Henrik Zetterberg ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Memory Performance ◽

Interactive Effect ◽

Amyloid Β ◽

Total Sample ◽

Increased Risk ◽

Latent Curve ◽

Latent Curve Models ◽

Ε4 Allele

ABSTRACTBackground: The ε4 allele of the apolipoprotein E (APOE) gene and low levels of cerebrospinal fluid (CSF) amyloid β-proteins 42 (Aβ) have previously been associated with increased risk of cognitive decline in old age. In this study we examine the interaction of these markers with episodic memory in a sample identified as having mild cognitive impairment (MCI).Methods: The sample (N = 149) was drawn from the Gothenburg MCI study and measured according to three free recall tests on three occasions spanning over four years. Second-order Latent Curve Models (LCM) were fitted to the data.Results: Analyses accounting for age, gender, education, APOE, Aβ42, and interaction between APOE and Aβ42 revealed that the ε4 allele was significantly associated with level of memory performance in the presence of low Aβ42 values (≤452 ng/L). Associations between memory performance and Aβ42 were significant among the ε4 carriers but not among the non-carriers. The Aβ42 marker was, however, significantly associated with changes in memory over the study time period in the total sample.Conclusion: The findings support the hypothesis of an interactive effect of APOE and Aβ42 for memory decline in MCI patients.

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Studying the Interplay Between Apolipoprotein E and Education on Cognitive Decline in Centenarians Using Bayesian Beta Regression

Frontiers in Genetics ◽

10.3389/fgene.2020.606831 ◽

2021 ◽

Vol 11 ◽

Author(s):

Qingyan Xiang ◽

Stacy Lynn Andersen ◽

Thomas T. Perls ◽

Paola Sebastiani

Keyword(s):

Cognitive Function ◽

Cognitive Decline ◽

Apolipoprotein E ◽

Neuropsychological Test ◽

Beta Regression ◽

Longitudinal Assessment ◽

Human Lifespan ◽

Increased Risk ◽

Negative Effect ◽

Positive Effect

Apolipoprotein E (APOE) is an important risk factor for cognitive decline and Alzheimer’s disease in aging individuals. Among the 3 known alleles of this gene: e2, e3, and e4, the e4 allele is associated with faster cognitive decline and increased risk for Alzheimer’s and dementia, while the e2 allele has a positive effect on longevity, and possibly on preservation of cognitive function. Education also has an important effect on cognition and longevity but the interplay between APOE and education is not well-characterized. Previous studies of the effect of APOE on cognitive decline often used linear regression with the normality assumption, which may not be appropriate for analyzing bounded and skewed neuropsychological test scores. In this paper, we applied Bayesian beta regression to assess the effect of APOE alleles on cognitive decline in a cohort of centenarians with longitudinal assessment of their cognitive function. The analysis confirmed the negative association between older age and cognition and the beneficial effect of education that persists even at the extreme of human lifespan in carriers of the e3 allele. In addition, the analysis showed an association between APOE and cognition that is modified by education. Surprisingly, an antagonistic interaction existed between higher education and APOE alleles, suggesting that education may reduce the positive effect of APOE e2 and increase the negative effect of APOE e4 at extreme old age.

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Association between ApoE ε4 Carrier Status and Cardiovascular Risk Factors on Mild Cognitive Impairment among Mexican Older Adults

Brain Sciences ◽

10.3390/brainsci11010068 ◽

2021 ◽

Vol 11 (1) ◽

pp. 68

Author(s):

Sara G. Aguilar-Navarro ◽

Itzel I. Gonzalez-Aparicio ◽

José Alberto Avila-Funes ◽

Teresa Juárez-Cedillo ◽

Teresa Tusié-Luna ◽

...

Keyword(s):

Risk Factors ◽

Older Adults ◽

Cognitive Impairment ◽

Cardiovascular Risk ◽

Mild Cognitive Impairment ◽

Cardiovascular Risk Factors ◽

Apoe Genotype ◽

Carrier Status ◽

Apoe Ε4 ◽

Increased Risk

Mild cognitive impairment (MCI) (amnestic or non-amnestic) has different clinical and neuropsychological characteristics, and its evolution is heterogeneous. Cardiovascular risk factors (CVRF), such as hypertension, diabetes, or dyslipidemia, and the presence of the Apolipoprotein E ε4 (ApoE ε4) polymorphism have been associated with an increased risk of developing Alzheimer’s disease (AD) and other dementias but the relationship is inconsistent worldwide. We aimed to establish the association between the ApoE ε4 carrier status and CVRF on MCI subtypes (amnestic and non-amnestic) in Mexican older adults. Cross-sectional study including 137 older adults (n = 63 with normal cognition (NC), n = 24 with amnesic, and n = 50 with non-amnesic MCI). Multinomial logistic regression models were performed in order to determine the association between ApoE ε4 polymorphism carrier and CVRF on amnestic and non-amnestic-MCI. ApoE ε4 carrier status was present in 28.8% participants. The models showed that ApoE ε4 carrier status was not associated neither aMCI nor naMCI condition. The interaction term ApoE ε4 × CVRF was not statistically significant for both types of MCI. However, CVRF were associated with both types of MCI and the association remained statistically significant after adjustment by sex, age, and education level. The carrier status of the ApoE genotype does not contribute to this risk.

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Multimodal measurement approach to identify individuals with mild cognitive impairment: study protocol for a cross-sectional trial

BMJ Open ◽

10.1136/bmjopen-2020-046879 ◽

2021 ◽

Vol 11 (5) ◽

pp. e046879

Author(s):

Bernhard Grässler ◽

Fabian Herold ◽

Milos Dordevic ◽

Tariq Ali Gujar ◽

Sabine Darius ◽

...

Keyword(s):

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Statistical Analysis ◽

Cognitive Decline ◽

Cognitive Performance ◽

Classification Accuracy ◽

Multimodal Approach ◽

Cross Sectional ◽

Age Related ◽

Age Related Cognitive Decline

IntroductionThe diagnosis of mild cognitive impairment (MCI), that is, the transitory phase between normal age-related cognitive decline and dementia, remains a challenging task. It was observed that a multimodal approach (simultaneous analysis of several complementary modalities) can improve the classification accuracy. We will combine three noninvasive measurement modalities: functional near-infrared spectroscopy (fNIRS), electroencephalography and heart rate variability via ECG. Our aim is to explore neurophysiological correlates of cognitive performance and whether our multimodal approach can aid in early identification of individuals with MCI.Methods and analysisThis study will be a cross-sectional with patients with MCI and healthy controls (HC). The neurophysiological signals will be measured during rest and while performing cognitive tasks: (1) Stroop, (2) N-back and (3) verbal fluency test (VFT). Main aims of statistical analysis are to (1) determine the differences in neurophysiological responses of HC and MCI, (2) investigate relationships between measures of cognitive performance and neurophysiological responses and (3) investigate whether the classification accuracy can be improved by using our multimodal approach. To meet these targets, statistical analysis will include machine learning approaches.This is, to the best of our knowledge, the first study that applies simultaneously these three modalities in MCI and HC. We hypothesise that the multimodal approach improves the classification accuracy between HC and MCI as compared with a unimodal approach. If our hypothesis is verified, this study paves the way for additional research on multimodal approaches for dementia research and fosters the exploration of new biomarkers for an early detection of nonphysiological age-related cognitive decline.Ethics and disseminationEthics approval was obtained from the local Ethics Committee (reference: 83/19). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.Trial registration numberClinicalTrials.gov, NCT04427436, registered on 10 June 2020, https://clinicaltrials.gov/ct2/show/study/NCT04427436.

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Subjective cognitive decline: The first clinical manifestation of Alzheimer's disease?

Dementia & Neuropsychologia ◽

10.1590/s1980-5764-2016dn1003002 ◽

2016 ◽

Vol 10 (3) ◽

pp. 170-177 ◽

Cited By ~ 22

Author(s):

Adalberto Studart Neto ◽

Ricardo Nitrini

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Clinical Manifestation ◽

Neurodegenerative Disorder ◽

Subjective Cognitive Decline ◽

Subjective Memory ◽

Increased Risk

ABSTRACT Background: Mild cognitive impairment is considered as the first clinical manifestation of Alzheimer's disease (AD), when the individual exhibits below performance on standardized neuropsychological tests. However, some subjects before having a lower performance on cognitive assessments already have a subjective memory complaint. Objective: A review about subjective cognitive decline, the association with AD biomarkers and risk of conversion to dementia. Methods: We performed a comprehensive non-systematic review on PubMed. The keywords used in the search were terms related to subjective cognitive decline. Results: Subjective cognitive decline is characterized by self-experience of deterioration in cognitive performance not detected objectively through formal neuropsychological testing. However, various terms and definitions have been used in the literature and the lack of a widely accepted concept hampers comparison of studies. Epidemiological data have shown that individuals with subjective cognitive decline are at increased risk of progression to AD dementia. In addition, there is evidence that this group has a higher prevalence of positive biomarkers for amyloidosis and neurodegeneration. However, Alzheimer's disease is not the only cause of subjective cognitive decline and various other conditions can be associated with subjective memory complaints, such as psychiatric disorders or normal aging. The features suggestive of a neurodegenerative disorder are: onset of decline within the last five years, age at onset above 60 years, associated concerns about decline and confirmation by an informant. Conclusion: These findings support the idea that subjective cognitive complaints may be an early clinical marker that precedes mild cognitive impairment due to Alzheimer's disease.

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The Influence of the Implementation of Total Quality Management and the Implementation of Good Governance on the Muzakki Trust (Study on Amil Zakat Institution in Batam City)

International Conference of Zakat ◽

10.37706/iconz.2019.197 ◽

2019 ◽

pp. 268-281

Author(s):

Cahyo Budi Santoso ◽

Ahmad Gamal

Keyword(s):

Quality Management ◽

Total Quality Management ◽

Good Governance ◽

Total Sample ◽

Significant Positive Effect ◽

Total Quality ◽

Negative Effect ◽

Positive Effect

Zakat becomes part of the obligations of Muslims who must be paid and given to those who are entitled to receive zakat. The distribution of zakat which is intended for the recipient and the amount of zakat is often not recorded accurately. There is a discrepancy between the amount of zakat and the number of recipients of zakat. Then a new breakthrough is needed through the implementation of toral quality management and the application of good governance so that it is expected that all incoming zakat and the number of recipients of zakat can be recorded. This study aims to examine the effect of the implementation of total quality management and the role of good governance on muzakki trust (a study at the Amil Zakat Institute in Batam City). The population in this study is the number of residents of the city of Batam in 2017 amounted to 1,062,250 inhabitants. Determination of the sample using the formula Hair, et al (2010) so that the total sample is 100 respondents. Data analysis using multiple linear regression with SPSS 23. The results of the study can be concluded that the implementation of total quality management has a significant positive effect on muzakki trust, the application of good governance has a significant negative effect on muzakki trust and the implementation of total quality management and the application of good governance simultaneously has a significant positive effect on muzakki trust.

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SURVIVAL ADVANTAGE OF APOE2

Innovation in Aging ◽

10.1093/geroni/igz038.2313 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S621-S621

Author(s):

Sudha Seshadri

Keyword(s):

Lower Risk ◽

Large Population ◽

Population Based ◽

European Ancestry ◽

Aggregated Data ◽

Risk Of Death ◽

Apoe Ε4 ◽

Increased Risk ◽

Ε4 Allele

Abstract Apolipoprotein E is a glycoprotein mediator and regulator of lipid transport and uptake. The APOE-ε4 allele has been associated with higher risk of Alzheimer’s disease and of mortality, but the effect of the less prevalent APOE-ε2 on survival remains elusive. We aggregated data of 38,537 individuals of European ancestry (mean age 65.5 years; 55.6% women) from six large population-based cohorts to determine the association of APOE-ε2, with survival in the general population. During a mean follow-up of 11.7 years, 17,021 individuals died. Compared with homozygous APOE-ε3 carriers, APOE-ε2 carriers were at lower risk of death (hazard ratio,95% confidence interval: 0.94,0.90-0.99; P=1.1*10-2), whereas APOE-ε4 carriers were at increased risk (HR 1.17,1.12-1.21; P=2.8*10-16). Risk was lowest for homozygous APOE-ε2 (HR 0.89,0.74-1.08), and highest for homozygous APOE-ε4 (HR 1.52,1.37-1.70). Results did not differ by sex. The association was unaltered after adjustment for baseline LDL or cardiovascular disease. Larger, multiethnic collaborations are ongoing.

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