Abdullah Lubnaa Badriyyah, Zhou Zhengyang, Alliey Ney Alex, Barber Robert, Hall James, O'Bryant Sid
Department of Family Medicine, University of North Texas Health Science Center (UNTHSC), Fort Worth, TX, United States.
Department of Population and Community Health, UNTHSC, Fort Worth, TX, United States.
Front Neurol. 2025 Jul 8;16:1627525. doi: 10.3389/fneur.2025.1627525. eCollection 2025.
Apolipoprotein allele 4 (APOE ε4) is associated with lower IQ scores during childhood and adolescence, but the influence of APOE ε4 and low IQ on late-life cognition is unknown. This study examines the association between APOE ε4 and cognitive outcomes based on premorbid intellectual ability (pIQ) and ethnic background.
Participants were drawn from the Health & Aging Brain Study-Health Disparities (HABS-HD), categorized by low ( ≤ -2.00) or average ( = 0.00 ± 1.00) pIQ based on word reading scores. Statistical analyses were conducted to evaluate whether APOE ε4 was associated with the cognitive domains of episodic memory, executive functioning, processing speed, and language by pIQ and ethnicity.
APOE ε4 was associated with worse cognitive performance across domains. In the overall sample analysis, the deleterious effect of ε4 on processing speed and executive functioning was stronger among those with low pIQ. In stratified analysis, the negative impact of APOE ε4 was stronger among non-Hispanic White individuals with low pIQ for episodic memory and Hispanic individuals with low pIQ for processing speed.
The influence of APOE genotype on cognitive outcomes is moderated by ethnicity and premorbid IQ, positioning low pIQ, a proxy for intellectual disability (ID), as a population more vulnerable to the negative effects of APOE ε4 in older adulthood.
The effect of Alzheimer's disease (AD) risk genes on cognitive performance may not mirror what is observed in AD-Down syndrome, highlighting the urgent need to expand AD research to reach more representative populations with I/DD.
载脂蛋白E4（APOE ε4）等位基因与儿童期和青少年期较低的智商得分相关，但APOE ε4和低智商对晚年认知的影响尚不清楚。本研究基于病前智力水平（pIQ）和种族背景，探讨APOE ε4与认知结果之间的关联。
参与者来自健康与衰老大脑研究-健康差异（HABS-HD），根据单词阅读分数分为低（≤ -2.00）或平均（= 0.00 ± 1.00）pIQ组。进行统计分析以评估APOE ε4是否与基于pIQ和种族的情景记忆、执行功能、处理速度和语言等认知领域相关。
APOE ε4与各领域较差的认知表现相关。在总体样本分析中，ε4对处理速度和执行功能的有害影响在低pIQ者中更强。在分层分析中，APOE ε4对情景记忆方面低pIQ的非西班牙裔白人个体以及处理速度方面低pIQ的西班牙裔个体的负面影响更强。
APOE基因型对认知结果的影响受种族和病前智商的调节，将低pIQ（作为智力残疾（ID）的一个指标）定位为在成年后期更容易受到APOE ε4负面影响的人群。
阿尔茨海默病（AD）风险基因对认知表现的影响可能与AD-唐氏综合征中观察到的情况不同，这凸显了迫切需要将AD研究扩展到更具代表性的智力障碍/发育障碍人群。
