Effects of <i>APOE</i> ε2 on different cognitive domains in the PUMCH dementia cohort

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.