The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Lancaster, Claire; Tabet, Naji; Rusted, Jennifer

doi:10.1016/j.neurobiolaging.2016.08.015

Cited by 14 publications

(9 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, it has been shown that younger carriers of ε 2 allele have more gray matter in the hippocampus and rely more on hippocampal-dependent strategies in tasks of navigation than noncarriers (Konishi et al., 2016). In contrast, other studies have found performance disadvantages in attention-related tasks in ε 2 carriers in middle and old age, compared with ε 3 carriers (Lancaster et al., 2016, Lancaster et al., 2017). Considering these complicated effects of the APOE ε 2 allele on cognitive performance, future studies should aim to examine the role of all APOE alleles on behavior, across aging, to provide a more comprehensive phenotypical description of this gene on behavior and its relationship with AD.…”

Section: Discussionmentioning

confidence: 56%

Dissociable effects of the apolipoprotein-E (APOE) gene on short- and long-term memories

Zokaei

Čepukaitytė

Board

et al. 2019

Neurobiology of Aging

View full text Add to dashboard Cite

Short- and long-term memory performance as a function of apolipoprotein-E (APOE) genotype was examined in older, healthy individuals using sensitive and comparable tasks to provide a more detailed description of influences of the ε4 allele (highest genetic risk factor for Alzheimer's disease) on memory. Older heterozygous and homozygous ε4 carriers and noncarriers performed 2 tasks of memory. Both tasks allowed us to measure memory for item identity and locations, using a sensitive, continuous measure of report. Long-term memory for object locations was impaired in ε4/ε4 carriers, whereas, paradoxically, this group demonstrated superior short-term memory for locations. The dissociable effects of the gene on short- and long-term memory suggest that the effect of genotype on these two types of memories, and their neural underpinnings, might not be co-extensive. Whereas the long-term memory impairment might be linked to preclinical Alzheimer's disease, the short-term memory advantage may reflect an independent, phenotypical effect of this allele on cognition.

show abstract

Section: Discussionmentioning

confidence: 56%

Dissociable effects of the apolipoprotein-E (APOE) gene on short- and long-term memories

Zokaei

Čepukaitytė

Board

et al. 2019

Neurobiology of Aging

View full text Add to dashboard Cite

show abstract

“…The inconsistent null pattern in some studies may derive from methodological issues, including differences in age, cognitive measures, sample size, and other cognitive risk factors [36,48]. It is noteworthy that the differential effects of APOE ε4 on cognition during different life stages represents an example of antagonistic pleiotropy [63]: a reduced or null negative effect is observed in middle age [50,64]; a reversed positive effect is observed in young adults [49]; and the effect size in the elderly is also affected by age [48]. Thus, any APOE -related study must take into account the interaction between age and the APOE gene.…”

Section: The Effects Of the Apoe Gene On Cognitive Function And Dementioning

confidence: 99%

The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk

Fan

Wan

et al. 2019

IJMS

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a progressive neurodegenerative disease. Although it has been studied for years, the pathogenesis of AD is still controversial. Genetic factors may play an important role in pathogenesis, with the apolipoprotein E (APOE) gene among the greatest risk factors for AD. In this review, we focus on the influence of genetic factors, including the APOE gene, the interaction between APOE and other genes, and the polygenic risk factors for cognitive function and dementia. The presence of the APOE ε4 allele is associated with increased AD risk and reduced age of AD onset. Accelerated cognitive decline and abnormal internal environment, structure, and function of the brain were also found in ε4 carriers. The effect of the APOE promoter on cognition and the brain was confirmed by some studies, but further investigation is still needed. We also describe the effects of the associations between APOE and other genetic risk factors on cognition and the brain that exhibit a complex gene–gene interaction, and we consider the importance of using a polygenic risk score to investigate the association between genetic variance and phenotype.

show abstract

“…The AP effect of APOE suggests that it would be fundamental to precisely define the specific periods of life to investigate and in which of those periods AP effects take place [145]. In fact, during earlier periods of life, the deleterious effects of APOE 4 vs. APOE 2 appear to be paradoxically reversed in some cases in respect to older age [31,129,146,147]. Although studies focusing on the allelic effects of APOE on young adults and children are relatively rare, a series of recent analyses evidenced an increased risk for poorer outcomes in APOE 2- vs. APOE 4-carriers in pediatric populations [130].…”

Section: Apoe Polymorphism In Normal and Pathologic Conditions Of Thementioning

confidence: 99%

“…language). Furthermore, we succinctly describe some of the possible molecular mechanistic aspects and biochemical pathways that have been proposed to explain the apparently paradoxical effects of APOE across the human lifespan [31].…”

Section: Introductionmentioning

confidence: 99%

Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan

Iacono

Feltis

2019

Aging

View full text Add to dashboard Cite

The central nervous system (CNS) is the cellular substrate for the integration of complex, dynamic, constant, and simultaneous interactions among endogenous and exogenous stimuli across the entire human lifespan. Numerous studies on aging-related brain diseases show that some genes identified as risk factors for some of the most common neurodegenerative diseases - such as the allele 4 of APOE gene (APOE4) for Alzheimer’s disease (AD) - have a much earlier neuro-anatomical and neuro-physiological impact. The impact of APOE polymorphism appears in fact to start as early as youth and early-adult life. Intriguingly, though, those same genes associated with aging-related brain diseases seem to influence different aspects of the brain functioning much earlier actually, that is, even from the neonatal periods and earlier. The APOE4, an allele classically associated with later-life neurodegenerative disorders as AD, seems in fact to exert a series of very early effects on phenomena of neuroplasticity and synaptogenesis that begin from the earliest periods of life such as the fetal ones.We reviewed some of the findings supporting the hypothesis that APOE polymorphism is an early modifier of various neurobiological aspects across the entire human lifespan - from the in-utero to the centenarian life - during both normal and pathological conditions of the brain.

show abstract

The APOE paradox: do attentional control differences in mid-adulthood reflect risk of late-life cognitive decline

Cited by 14 publications

References 71 publications

Dissociable effects of the apolipoprotein-E (APOE) gene on short- and long-term memories

Dissociable effects of the apolipoprotein-E (APOE) gene on short- and long-term memories

The Contribution of Genetic Factors to Cognitive Impairment and Dementia: Apolipoprotein E Gene, Gene Interactions, and Polygenic Risk

Impact of Apolipoprotein E gene polymorphism during normal and pathological conditions of the brain across the lifespan

Contact Info

Product

Resources

About