Clinical Manifestations

Background: Previous studies on APOE have mostly focused on APOE ε4, while less attention has been paid to APOE ε2. The aim of this study was to clarify the effect of APOE ε2 on different cognitive domains in dementia patients.

Method: All subjects were from the Peking Union Medical College Hospital (PUMCH) dementia cohort and included clinical diagnoses of AD, VaD, FTLD, and LBD. All included individuals had completed the neuropsychological assessment. Genotypes were used to bin participants into five groups based on carrier status: ε2 carriers (ε2/ε2 or ε2/ε3), ε2/ε4 carriers, ε3/ε3 carriers, ε3/ε4 carriers, and ε4/ε4 carriers. The effect of APOE ε2 on different cognitive domains of the patients with dementia was assessed by using multivariate regression models.

Result: A total of 348 dementia patients were included in this study, with a mean age of 68.4± 9.8 years, 69.3% with AD, 14.4% with VaD, 10.1% with FTLD, and 6.3% with DLB. 19.5% were ε2 carriers, 3.4% were ε2/ε4 carriers, 30.7% were ε3/ε3 carriers, 32.3% were ε3/ε4 carriers, and 14.1% were ε4/ε4 carriers. Compared to ε3/ε3 carriers, ε2 carriers were more successful in MOCA (β = 1.93, P = 0.016), trail making test part A (β = 1.18, P = 0.025), nonverbal memory (β = 1.08, P = 0.003), AVLT 5 (β = 0.27, P = 0.039), episodic memory (β = 0.41, P = 0.005), calculation (β = 1.05, P = 0.045) and word fluency (β = 1.82, P = 0.03). Compared to ε4/ε4 carriers, ε2 carriers performed better in nonverbal memory (β = 1.59, P<0.001), AVLT 4 (β = 0.68, P<0.001), AVLT 5 (β = 0.62, P<0.001), associative learning test (β = 0.57, P<0.001), episodic memory (β = 0.46, P = 0.007) performed better. When adjusted for clinical diagnosis, the above significant differences remained statistically significant. While ε2/ε4 carriers performed better in associative learning (β = 1.38, P<0.001) compared to ε3/ε3, visuospatial (β = -1.94, P = 0.020) function was worse than ε3/ε3 carriers. Compared to ε4/ε4, ε2/ε4 carriers performed worse in similarity test and visuospatial function, while in verbal memory performed better CONCLUSION: The present study found complex effects of APOE ε2 and APOE ε2/ε4 on cognitive domains that varied according to the selected control group, whereas different clinical diagnoses did not seem to influence their effects.