ORIGINAL RESEARCH article
Front. Neurol.
Sec. Dementia and Neurodegenerative Diseases
Volume 16 - 2025 | doi: 10.3389/fneur.2025.1627525
This article is part of the Research TopicBlood, Cerebrospinal Fluid, and Vascular Biomarkers for DementiaView all 19 articles
Low premorbid IQ may exacerbate the cognitive effects of apolipoprotein ε4 (APOE ε4): A multi-ethnic cross-sectional study from HABS-HD
Provisionally accepted
- 1University of North Texas Health Science Center, Fort Worth, United States
- 2University of Texas Rio Grande Valley, Edinburgh, United States
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Introduction: 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 makeup. Methods: Participants were drawn from the Health & Aging Brain Study -Health Disparities (HABS-HD), categorized by low (z ≤ -2.00) or average (z = 0.00 ± 1.00) pIQ based on word reading scores. Statistical analyses were conducted to evaluate whether APOE4 was associated with cognitive domains of episodic memory, executive functioning, processing speed, and language by pIQ and ethnicity. Results: 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 Whites with low pIQ for episodic memory and Hispanics with low pIQ for processing speed. Discussion: The influence of APOE genotype on cognitive outcomes is moderated by ethnicity and premorbid IQ, positioning low pIQ, a proxy for ID, as a population more vulnerable to the negative effects of APOE ε4 in older adulthood. Conclusion: The effect of 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.
Keywords: Alzheimer's disease (AD), apolipoprotein (ApoE), Cognition, Low IQ, Intellectual Disability
Received: 12 May 2025; Accepted: 18 Jun 2025.
Copyright: © 2025 Abdullah, Zhou, Alliey, Hall, Barber and O'Bryant. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Lubnaa Badriyyah Abdullah, University of North Texas Health Science Center, Fort Worth, United States
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