Differential Associations of Apolipoprotein E ?4 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 ?4 allele of the apolipoprotein E gene (APOE ?4) is associated with an additional risk for AD. In typical development, there is evidence that the APOE ?4 genotype is associated with an early cognitive advantage. Here we investigate associations of APOE ?4 with attention across the life span of individuals with DS. Objective:To investigate associations between APOE ?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 (?4 carrier vs ?4 noncarrier) and attentional abilities. Exposure:APOE status (?4 carrier vs ?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 ?4 carriers and ?4 noncarriers for children and adults separately. Results:The child sample comprised 23 ?4 carriers and 57 ?4 noncarriers. The adult sample comprised 61 ?4 carriers and 179 ?4 noncarriers. For the children, a significant difference between trajectory intercepts (?p2?=?0.14) indicated that ?4 carriers (B?=?100.24 [95% CI, 18.52-181.96]) exhibited an attentional advantage over ?4 noncarriers (B?=?314.78 [95% CI, 252.17-377.39]). There was an interaction between APOE status and age (?p2?=?0.10); while the gap effect decreased with age for ?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 ?4 carriers (B?=?0.77 [95% CI, -1.57 to 3.12]). For the adults, there was no main effect of ?4 carrier status, but there was an interaction between APOE status and age (B?=?0.02 [95% CI, 0.004-0.07]), so that ?4 carriers had poorer attentional ability than ?4 noncarriers at older ages. Conclusions and Relevance:APOE ?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.

SUBMITTER: D'Souza H 

PROVIDER: S-EPMC7522696 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature