Sex influences the effects of APOE genotype and Alzheimer’s diagnosis on neuropathology and memory

Background: Apolipoprotein E (APOE) is a prominent genetic risk factor for Alzheimer’s disease (AD) and a frequent target for associations with non-demented and cognitively impaired aging. APOE offers a unique opportunity to evaluate two dichotomous comparisons and selected gradations of APOE risk. Some evidence suggests that APOE effects may differ by sex and emerge especially in interaction with other AD-related biomarkers (e.g., vascular health). Methods: Longitudinal trajectories of non-demented adults (n = 632, 67% female, Mage = 68.9) populated a 40-year band of aging. Focusing on memory performance and individualized memory trajectories, a sequence of latent growth models was tested for predictions of (moderation between) APOE and pulse pressure (PP) as stratified by sex. The analyses (1) established robust benchmark PP effects on memory trajectories, (2) compared predictions of alternative dichotomous groupings (ε4- vs ε4+, ε2- vs ε2+), and (3) examined precision-based predictions by disaggregated APOE genotypes. Results: Healthier (lower) PP was associated with better memory performance and less decline. Therefore, all subsequent analyses were conducted in the interactive context of PP effects and sex stratification. The ε4-based dichotomization produced no differential genetic predictions. The ε2-based analyses showed sex differences, including selective protection for ε2-positive females. Exploratory follow-up disaggregated APOE genotype analyses suggested selective ε2 protection effects for both homozygotic and heterozygotic females. Conclusion: Precision analyses of AD genetic risk will advance the understanding of underlying mechanisms and improve personalized implementation of interventions.

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Modulation of Retinal Arteriolar Central Reflection by APOE Genotype

Current Alzheimer Research ◽

10.2174/1567205014666170309115016 ◽

2017 ◽

Vol 14 (9) ◽

Cited By ~ 3

Author(s):

Shaun Frost ◽

Alauddin Bhuiyan ◽

David Offerman ◽

James D. Doecke ◽

S. Lance Macaulay ◽

...

Keyword(s):

Apoe Genotype ◽

Retinal Arteriolar

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Race-Related Association between APOE Genotype and Alzheimer’s Disease: A Systematic Review and Meta-Analysis

Journal of Alzheimer s Disease ◽

10.3233/jad-210549 ◽

2021 ◽

pp. 1-10

Author(s):

Wei Qin ◽

Wenwen Li ◽

Qi Wang ◽

Min Gong ◽

Tingting Li ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Black People ◽

Late Onset ◽

Meta Analysis ◽

Group Analysis ◽

Apoe Genotype ◽

Cochrane Library ◽

Data Sets ◽

Apoe Genotypes

Background: The global race-dependent association of Alzheimer’s disease (AD) and apolipoprotein E (APOE) genotype is not well understood. Transethnic analysis of APOE could clarify the role of genetics in AD risk across populations. Objective: This study aims to determine how race and APOE genotype affect the risks for AD. Methods: We performed a systematic search of PubMed, Embase, Web of Science, and the Cochrane Library since 1993 to Aug 25, 2020. A total of 10,395 reports were identified, and 133 were eligible for analysis with data on 77,402 participants. Studies contained AD clinical diagnostic and APOE genotype data. Homogeneous data sets were pooled in case-control analyses. Odds ratios and 95% confidence intervals for developing AD were calculated for populations of different races and APOE genotypes. Results: The proportion of APOE genotypes and alleles differed between populations of different races. Results showed that APOE ɛ4 was a risk factor for AD, whereas APOE ɛ2 protected against it. The effects of APOE ɛ4 and ɛ2 on AD risk were distinct in various races, they were substantially attenuated among Black people. Sub-group analysis found a higher frequency of APOE ɛ4/ɛ4 and lower frequency of APOE ɛ3/ɛ3 among early-onset AD than late-onset AD in a combined group and different races. Conclusion: Our meta-analysis suggests that the association of APOE genotypes and AD differ between races. These results enhance our understanding of APOE-related risk for AD across race backgrounds and provide new insights into precision medicine for AD.

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Digital Technology Differentiates Graphomotor and Information Processing Speed Patterns of Behavior

Journal of Alzheimer s Disease ◽

10.3233/jad-201119 ◽

2021 ◽

Vol 82 (1) ◽

pp. 17-32 ◽

Cited By ~ 1

Author(s):

Stacy L. Andersen ◽

Benjamin Sweigart ◽

Nancy W. Glynn ◽

Mary K. Wojczynski ◽

Bharat Thyagarajan ◽

...

Keyword(s):

Information Processing ◽

Physical Function ◽

Digital Technology ◽

Test Scores ◽

Neuropsychological Test ◽

Apoe Genotype ◽

Digital Data ◽

Cognitive Test ◽

Digit Symbol Substitution Test ◽

Information Processing Speed

Background: Coupling digital technology with traditional neuropsychological test performance allows collection of high-precision metrics that can clarify and/or define underlying constructs related to brain and cognition. Objective: To identify graphomotor and information processing trajectories using a digitally administered version of the Digit Symbol Substitution Test (DSST). Methods: A subset of Long Life Family Study participants (n = 1,594) completed the DSST. Total time to draw each symbol was divided into ‘writing’ and non-writing or ‘thinking’ time. Bayesian clustering grouped participants by change in median time over intervals of eight consecutively drawn symbols across the 90 s test. Clusters were characterized based on sociodemographic characteristics, health and physical function data, APOE genotype, and neuropsychological test scores. Results: Clustering revealed four ‘thinking’ time trajectories, with two clusters showing significant changes within the test. Participants in these clusters obtained lower episodic memory scores but were similar in other health and functional characteristics. Clustering of ‘writing’ time also revealed four performance trajectories where one cluster of participants showed progressively slower writing time. These participants had weaker grip strength, slower gait speed, and greater perceived physical fatigability, but no differences in cognitive test scores. Conclusion: Digital data identified previously unrecognized patterns of ‘writing’ and ‘thinking’ time that cannot be detected without digital technology. These patterns of performance were differentially associated with measures of cognitive and physical function and may constitute specific neurocognitive biomarkers signaling the presence of subtle to mild dysfunction. Such information could inform the selection and timing of in-depth neuropsychological assessments and help target interventions.

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Vitamin D Levels, APOE Allele, and MRI Volumetry Assessed by NeuroQuant in Norwegian Adults with Cognitive Symptoms

Journal of Alzheimer s Disease ◽

10.3233/jad-201018 ◽

2021 ◽

Vol 79 (1) ◽

pp. 311-321

Author(s):

Jelena Zugic Soares ◽

Renate Pettersen ◽

Jūratė Šaltytė Benth ◽

Karin Persson ◽

Carsten Strobel ◽

...

Keyword(s):

Vitamin D ◽

Late Onset ◽

Apoe Genotype ◽

Serum Levels ◽

Grey Matter Volume ◽

Cognitive Symptoms ◽

Cross Sectional ◽

Brain Volumes ◽

Vitamin D Levels ◽

Mri Volumetry

Background: Allele ɛ4 of the apolipoprotein (APOE ∈4) gene is the strongest known genetic risk factor for late-onset sporadic Alzheimer’s disease. A possible relationship between vitamin D and APOE is not yet clear. Objective: In this exploratory, cross-sectional study, we examined the association between serum levels of 25-hydroxyvitamin D [25(OH)D] and brain volumes and the associations of both serum levels of 25(OH)D and APOE polymorphism to brain volumes in 127 persons (mean age 66 years) with cognitive symptoms. Methods: All subjects were examined with fully automated software for MRI volumetry, NeuroQuant. Results: After adjustment for relevant covariates, higher serum 25(OH)D levels were associated with greater volumes of cortical gray matter on both left (p = 0.02) and right (p = 0.04) sides. When both 25(OH)D levels and APOE genotype were used as the main covariates, no significant associations were found between vitamin D level and brain volume in any of the 11 brain regions. In adjusted models, only homozygous but not heterozygous APOE ∈4 allele carriers had significantly larger inferior lateral ventricles (p = 0.003) and smaller hippocampal volume (p = 0.035) than those without ɛ4. Homozygous APOE ∈4 carriers also had significantly higher vitamin D levels (p = 0.009) compared to persons without the APOE ∈4 allele. Conclusion: Higher vitamin D levels might have a preserving effect on cortical grey matter volume.

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Insomnia symptom severity and cognitive performance: Moderating role of APOE genotype

Alzheimer s & Dementia ◽

10.1002/alz.12405 ◽

2021 ◽

Author(s):

Andrée‐Ann Baril ◽

Alexa S. Beiser ◽

Erlan Sanchez ◽

Vincent Mysliwiec ◽

Susan Redline ◽

...

Keyword(s):

Cognitive Performance ◽

Symptom Severity ◽

Apoe Genotype ◽

Insomnia Symptom ◽

Moderating Role

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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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