WHITE MATTER, AGE, APOE-E4, AND EPISODIC MEMORY IN MIDLIFE ADULTS AT HEIGHTENED RISK FOR ALZHEIMER’S DISEASE - Abstract

Sep 29, 2026

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Episodic memory (EM) decline is an early cognitive symptom of Alzheimer’s disease (AD). White matter microstructural integrity (WMI) supports EM, but whether age and APOE-e4 genotype modify the WMI–EM relationship in midlife before symptom onset remains unclear. The study tested independent moderation by age and APOE-e4 carriage in cognitively normal middle-aged adults with family history of AD (FH+), using DTI in fornix and hippocampal cingulum and EM tasks (AVLT-IR/DR).

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages2

Reading Time5 min

AccessFree to download

Background

Study Aim

Methods

Participants and Genotyping

Imaging and Cognitive Measures

Results

WMI and APOE-e4 Interactions

Age Moderation of WMI–EM Links

Conclusions

1280 Innovation in Aging, 2025, Vol. 9, No. S2 Abstract citation ID: igaf122.4272 WHITE MATTER, AGE, APOE-E4, AND EPISODIC MEMORY IN MIDLIFE ADULTS AT HEIGHTENED RISK FOR ALZHEIMER’S DISEASE Chadsley Wessinger1, Jennifer Etnier1, Kyoung Shin Park2, Samantha DuBois3, Samuel Kibildis4, Jarod Vance5, Brittany Armstrong1, and Alexis Slutsky-Ganesh6, 1. University of North Carolina at Greensboro, Greensboro, North Carolina, United States, 2. Emory University School of Medicine, Atlanta, Georgia, United States, 3. Appalachian State University, Boone, North Carolina, United States, 4. Athens-Clarke County Unified Government, Athens, Georgia, United States, 5. Longwood University, Farmville, Virginia, United States, 6. North Carolina Agricultural and Technical State University, Greensboro, North Carolina, United States Episodic memory (EM) decline is an early cognitive symptom of Alzheimer’s disease (AD) . White matter microstructural Innovation in Aging, 2025, Vol. 9, No. S2 1281 integrity (WMI) supports EM, but it is unclear if AD risk factors of age and apolipoprotein epsilon-4 genotype (APOE-e4) influence the relationship between WMI and EM at midlife prior to AD symptom onset. We investigated if age andAPOE-e4 carriage independently moderated the relationship between WMI and EMin cognitively normal middle-aged adults with a family history of AD (FH+). Participants (N=109[84% female]; Mage=56.2±6.0 years) provided saliva samples for APOE-e4 genotyping (e4 non-carriers/carriers=61/48) and completed diffusion tensor imaging (DTI) and cognitive testing. DTI scalars—mean diffusivity (MD), axial diffusivity (AxD), and radial diffusivity (RD)—were estimated in the fornix and hippocampal cingulum (CGH), tracts critical for EM. EM was assessed with Auditory Verbal Learning Task Immediate Recall (AVLT-IR) and Delayed Recall (AVLT-DR). Moderated regression models were fitted; significant (p<.05) and near-significant (p<.10) interactions were followed by simple slope analyses. No WMI*APOE-e4 carriage interactions were significant (p’s>.10).Age moderated the WMI–AVLT-IR associations for CGH AxD (left: p=.027, right: p=.011), MD (left: p=.011, right: p=.005), and RD (right: p=.044); and the WMI–AVLT-DR associations for CGHAxD (left: p=.009, right: p=.010) and MD (left: p=.014, right: p=.011) . In the oldest of participants (Mage=62.7±1.9 years), bilateral CGH AxD and MD negatively predicted AVLT-IR (p’s=.011-.023) andAVLT-DR (p’s=.012-.062) performance. In cognitively normal middle-aged adults with FH+, negative relationships between CGH WMI and EM were observed, suggesting the possibility of pre-clinical associations between brain health and cognitive behavior.

FAQs

What was the main research question of the study?

The study investigated whether age and APOE-e4 carriage independently moderated the relationship between white matter microstructural integrity and episodic memory in midlife adults before AD symptom onset.

How were APOE-e4 status and white matter integrity assessed?

Participants provided saliva for APOE-e4 genotyping, and diffusion tensor imaging (DTI) estimated white matter microstructural measures (MD, AxD, RD) in the fornix and hippocampal cingulum.

Which cognitive tests were used to measure episodic memory?

Episodic memory was assessed with the Auditory Verbal Learning Task, including Immediate Recall (AVLT-IR) and Delayed Recall (AVLT-DR).

What did the results suggest about brain health and cognition in FH+ adults?

In cognitively normal middle-aged adults with FH+, negative relationships between hippocampal cingulum WMI and EM were observed, suggesting potential pre-clinical associations between brain health and cognitive behavior.

Sep 29, 2026

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