Differential Associations of Apolipoprotein E ε4 Genotype With Attentional Abilities Across the Life Span of Individuals With Down Syndrome
Authors: Hana D’Souza, Luke Mason, Kin Y. Mok, Carla M. Startin, Sarah Hamburg, Rosalyn Hithersay, R. Asaad Baksh, John Hardy, Andre Strydom, Michael S. C. Thomas
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Risk of Alzheimer disease (AD) is particularly high for individuals with Down syndrome (DS). The ε4 allele of the apolipoprotein E gene (<i>APOE </i>ε4) is associated with an additional risk for AD. In typical development, there is evidence that the<i>APOE </i>ε4 genotype is associated with an early cognitive advantage. Here we investigate associations of<i>APOE </i>ε4 with attention across the life span of individuals with DS. <h3>Objective</h3> To investigate associations between<i>APOE </i>ε4 and attentional abilities in young children and in adults with DS. <h3>Design, Settings, and Participants</h3> 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<i>APOE</i>status (ε4 carrier vs ε4 noncarrier) and attentional abilities. <h3>Exposure</h3> <i>APOE</i>status (ε4 carrier vs ε4 noncarrier). <h3>Main Outcomes and Measures</h3> 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. <h3>Results</h3> 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 (η<sub>p</sub><sup>2</sup> = 0.14) indicated that ε4 carriers (<i>B</i> = 100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ε4 noncarriers (<i>B</i> = 314.78 [95% CI, 252.17-377.39]). There was an interaction between<i>APOE</i>status and age (η<sub>p</sub><sup>2</sup> = 0.10); while the gap effect decreased with age for ε4 noncarriers (<i>B</i> = −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 (<i>B</i> = 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<i>APOE</i>status and age (<i>B</i> = 0.02 [95% CI, 0.004-0.07]), so that ε4 carriers had poorer attentional ability than ε4 noncarriers at older ages. <h3>Conclusions and Relevance</h3> <i>APOE </i>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<i>APOE</i>across the life span is an important step toward future interventions.