Abstract
Objective: To investigate whether APOE ε4 affects the association of verbal memory with neurodegeneration presented by the hippocampal volume/intracranial volume ratio (HpVR).Methods: The study sample included 371 individuals with normal cognition (NC), 725 subjects with amnestic mild cognitive impairment (aMCI), and 251 patients with mild Alzheimer’s disease (AD) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) who underwent the rey auditory verbal learning test (RAVLT). Multiple linear regression models were conducted to assess the effect of the APOE ε4∗HpVR interaction on RAVLT in all subjects and in each diagnostic group adjusting for age, gender and educational attainment, and global cognition.Results: In all subjects, there was no significant APOE ε4 × HpVR interaction for immediate recall or delayed recall (p > 0.05). However, in aMCI subjects, there was a significant APOE ε4 × HpVR interaction for delayed recall (p = 0.008), but not immediate recall (p = 0.15). More specifically, the detrimental effect of APOE ε4 on delayed recall altered by HpVR such that this effect was most evident among subjects with small to moderate HpVR, but this disadvantage was absent or even reversed among subjects with larger HpVR. No significant interaction was observed in the NC or AD group.Conclusion: These findings highlight a potential role of APOE ε4 status in affecting the association of hippocampus size with delayed recall memory in the early stage of AD.
Highlights
The effect of the apolipoprotein E ε4 (APOE ε4) allele on cognitive abilities is complicated
In diagnosis-stratified analyses, the HpVR by APOE ε4 status interaction was significant for delayed recall in an aMCI group (p = 0.008), but not immediate recall (p = 0.15)
No significant difference in immediate (p = 0.8) or delayed recall (p = 0.3) was found between APOE ε4 carriers and non-carriers, and HpVR was not associated with immediate recall (p = 0.7) or delayed recall (p = 0.6) (Table 4)
Summary
The effect of the apolipoprotein E ε4 (APOE ε4) allele on cognitive abilities is complicated. A previous study showed that the APOE ε4 allele contributes to the reduction of hippocampal volume in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) (Khan et al, 2017). A recent study revealed that hippocampal volume was positively associated with episodic memory in cognitively normal old individuals with APOE ε4 homozygotes (Lim et al, 2017). It is unknown whether the APOE ε4 allele has antagonistic pleiotropic effects on the association of hippocampal volumes with episodic memory across the AD continuum. Our primary goal was to examine whether the APOE ε4 allele modulates the relationship between hippocampal volumes and verbal memory in subjects with NC, MCI, and mild AD from the Alzheimer’s disease neuroimaging initiative (ADNI) dataset
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