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bioRxiv · 10.1101/2025.09.30.679544

APOE4 carriers resistant to cognitive decline show unique relationships between cerebrovascular response to exercise and dual-task cognitive-balance performance

Palmer, J. A.·Billinger, S.
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Abstract

BACKGROUNDEmerging research indicates cognitive dual-tasking is an early marker for cognitive impairment, with particular implications for Apolipoprotein E4 (APOE4) carriers who are at higher genetic risk for Alzheimers disease. While APOE4 carriers typically show accelerated cognitive decline and impaired cerebrovascular function with aging, exceptions to this norm exist and may provide insights into resilience mechanisms. The relationship between cerebrovascular response and cognitive-motor dual-task performance in cognitively-normal APOE4 carriers who maintain preserved function remains unclear. METHODSThirty cognitively-normal older adults (76{+/-}4 years, 8 APOE4 carriers, 22 noncarriers) completed clinical balance and cognitive testing under single-task and dual-task conditions. Balance performance was assessed as distance traversed during challenging beam walking. Cognitive performance was assessed as response time during an auditory Stroop test. Transcranial Doppler ultrasound measured cerebrovascular response to moderate-intensity aerobic exercise. We tested group differences in cognitive-balance dual task performance and relationships between cerebrovascular response and dual-task interference (DTI) in balance and cognitive domains, and effects of APOE4 genotype on these relationships. RESULTSNo differences in cerebrovascular response or dual-task performance were observed between APOE4 carriers and noncarriers. However, APOE4 carriers displayed unique cerebrovascular-behavioral relationships. In APOE4 carriers, higher cerebrovascular response to exercise was associated with less balance DTI (r=0.839, p=0.009) and less cognitive DTI (r=0.832, p=0.020), while no relationships were observed in noncarriers (p>0.187). CONCLUSIONSCognitively-normal APOE4 carriers with preserved cognitive-balance dual-task function represent exceptions that may model aging resilience mechanisms. The unique cerebrovascular-behavioral relationships suggest that maintaining cerebrovascular function provides preliminary support for neuromotor and neurocognitive resilience to dual-task challenges in genetically vulnerable populations.

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Palmer, J. A., Billinger, S.. 2025-10-01. APOE4 carriers resistant to cognitive decline show unique relationships between cerebrovascular response to exercise and dual-task cognitive-balance performance. https://doi.org/10.1101/2025.09.30.679544

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