Differential Associations of Apolipoprotein e ϵ4 Genotype with Attentional Abilities Across the Life Span of Individuals with Down Syndrome

Abstract

Importance: Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The ϵ4 allele of the apolipoprotein E gene (APOE ϵ4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE ϵ4 genotype is associated with an early cognitive advantage. Here we investigate associations of APOE ϵ4 with attention across the life span of individuals with DS. Objective: To investigate associations between APOE ϵ4 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 (ϵ4 carrier vs ϵ4 noncarrier) and attentional abilities. Exposure: APOE status (ϵ4 carrier vs ϵ4 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 ϵ4 carriers and ϵ4 noncarriers for children and adults separately. Results: The child sample comprised 23 ϵ4 carriers and 57 ϵ4 noncarriers. The adult sample comprised 61 ϵ4 carriers and 179 ϵ4 noncarriers. For the children, a significant difference between trajectory intercepts (ηp2= 0.14) indicated that ϵ4 carriers (B = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ϵ4 noncarriers (B = 314.78 [95% CI, 252.17-377.39]). There was an interaction between APOE status and age (ηp2= 0.10); while the gap effect decreased with age for ϵ4 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 ϵ4 carriers (B = 0.77 [95% CI, -1.57 to 3.12]). For the adults, there was no main effect of ϵ4 carrier status, but there was an interaction between APOE status and age (B = 0.02 [95% CI, 0.004-0.07]), so that ϵ4 carriers had poorer attentional ability than ϵ4 noncarriers at older ages. Conclusions and Relevance: APOE ϵ4 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..