Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome

Question What are the associations between the Alzheimer disease risk allele apolipoprotein E (APOE) epsilon 4 and attention across the life span of individuals with Down syndrome? Findings In a cross-sectional study including 80 young children and 240 adults with Down syndrome, an advantage was observed in attention for epsilon 4 carriers relative to epsilon 4 noncarriers among young children. Among young adults, no attentional advantage was observed in epsilon 4 carriers, and possession of an epsilon 4 allele was associated with a disadvantage among older adults. Meaning Although APOE epsilon 4 is a risk allele for Alzheimer disease later in life, it may be associated with an attentional advantage in the early development of individuals with Down syndrome. Importance Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The epsilon 4 allele of the apolipoprotein E gene (APOE epsilon 4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE epsilon 4 genotype is associated with an early cognitive advantage. Here we investigate associations of APOE epsilon 4 with attention across the life span of individuals with DS. Objective To investigate associations between APOE epsilon 4 and attentional abilities in young children and in adults with DS. Design, Settings, and Participants In this cross-sectional study, data were collected from 80 young children with DS (8-62 months of age) and 240 adults with DS (16-71 years of age) during the period from 2013 to 2018 at a research center to examine the association between APOE status (epsilon 4 carrier vs epsilon 4 noncarrier) and attentional abilities. Exposure APOE status (epsilon 4 carrier vs epsilon 4 noncarrier). Main Outcomes and Measures For the children, attentional ability was assessed using an eye-tracking paradigm, the gap-overlap task; the size of the gap effect was the primary outcome. For the adults, attentional ability was assessed using the CANTAB simple reaction time task; the standard deviation of response time latencies was the primary outcome. Cross-sectional developmental trajectories were constructed linking attentional ability with age in epsilon 4 carriers and epsilon 4 noncarriers for children and adults separately. Results The child sample comprised 23 epsilon 4 carriers and 57 epsilon 4 noncarriers. The adult sample comprised 61 epsilon 4 carriers and 179 epsilon 4 noncarriers. For the children, a significant difference between trajectory intercepts (eta(2)(p) = 0.14) indicated that epsilon 4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over epsilon 4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]). There was an interaction between APOE status and age (eta(2)(p) = 0.10); while the gap effect decreased with age for epsilon 4 noncarriers (B = -4.58 [95% CI, -6.67 to -2.48]), reflecting the development of the attention system, there was no change across age in epsilon 4 carriers (B = 0.77 [95% CI, -1.57 to 3.12]). For the adults, there was no main effect of epsilon 4 carrier status, but there was an interaction between APOE status and age (B = 0.02 [95% CI, 0.004-0.07]), so that epsilon 4 carriers had poorer attentional ability than epsilon 4 noncarriers at older ages. Conclusions and Relevance APOE epsilon 4 is associated with an attentional advantage early in development and a disadvantage later in life for individuals with DS, similar to the pattern reported in typical development. Understanding the differential role of APOE across the life span is an important step toward future interventions. This cross-sectional study investigates the associations between apolipoprotein E (APOE) epsilon 4 genotype and attentional abilities across the life span of individuals with Down syndrome.