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APOE ε4 allele is the strongest predictor of Alzheimer’s disease (AD) risk, but its role in the association between the deep grey matter volume and cognitive impairment is still unclear. This study investigated the effects of APOE ε4 allele on this association in non-demented elders. We enrolled 24 patients with mild cognitive impairment (MCI) and 28 normal controls (NC), who underwent the whole brain 3DT I W MRI scanning, an APOE genotype test, and neuropsychological tests. The right thalamus ( p  = 0.026), the left pallidum ( p  = 0.026), and the bilateral amygdala (left  p  = 0.042, right  p  = 0.048) atrophied in MCI, and their volume were positively correlated with the cognitive scores (MoCA) ( p  &lt; 0.05). Furthermore, the general liner regression model suggested that the correlation between the right thalamus and the putamen volume with MoCA scores was different in the APOE ε4 carriers and non- carriers. Compared with the non APOEε4 carriers, the right thalamus atrophied more rapidly when the cognition decline in APOE ε4 carriers, while the right putamen compensatory expansion to slow the rate of cognitive decline although failed. This suggested that the right putamen showed stronger compensation by increasing the volume at the early stage of cognitive impairments in the APOE ε4 carriers, while this compensatory change had been disappeared in the right thalamus. In conclusion, APOE ε4 allele modifies the correlation between the right thalamus, the right putamen, and MoCA scores, and it has a potential selective effect on the relationship between cognition and brain structures to some extent in non-demented elders.

APOE ε4 allele modified the correlation between deep grey matter volume and cognitive performance in non-demented elders