Association between apolipoprotein E ε4 and longitudinal cognitive decline: nested case-control study among chinese community-dwelling elders

Background/aims: Cognitive decline in the elderly is an early predictor of dementia. The apolipoprotein E (APOE) ε4 allele is considered an important genetic determinant of Alzheimer's disease (AD), and strongly suspected to play a role in cognitive variation. However, its effects upon predicting the progression of cognitive decline more generally remain unclear. Our aim was to explore the role of APOE ε4 in longitudinal cognitive decline, considering sociodemographics, vascular disease, and lipid profile.

Methods: We chose a nested case-control design, and prospectively collected demographic and clinical data, determined APOE genotypes, and obtained follow-up information on cognitive variation (measured by a spectrum of cognitive tests) for 3 years. Cognitive decline was predefined as an increase in Clinical Dementia Rating Scale class, or at least a 4-point decrease (>1 SD) in MMSE, between baseline and follow-ups.

Results: Among 600 follow-up subjects with mild cognitive impairment and aged 65 years or older, 114 pairs of cognitive decline and stable subjects were identified and matched for sex, age, and educational level in a 1:1 ratio. The APOE ε4 frequency in the cognitive decline group was significantly higher than that in the stable group (p < 0.05), while the APOE ε2 and ε3 prevalence in the cognitive decline group did not differ significantly from that in controls (p > 0.05). At the first follow-up, modest but significant declines only in the memory domain were associated with APOE ε4. At the last follow-up, significant associations were noted between APOE ε4 and cognitive decline from 5 of the 6 cognitive outcomes, which included story recall, memory, spatial recognition, naming, and sustained attention. Conditional logistic regression showed that the presence of APOE ε4 was significantly associated with the cognitive decline group, as compared to the stable group, adjusting for vascular diseases and lipid profile.

Conclusions: APOE ε4 offered information on the risk of cognitive decline in this longitudinal study, and may exert detectable effects early in a long prodromal AD trajectory.