Association between Apolipoprotein E epsilon 4 and Longitudinal Cognitive Decline: Nested Case-Control Study among Chinese Community-Dwelling Elders

作者：Ma, Fei^*; Wang, Jianhua; Miao, Rujuan; Zhao, Wei; Wang, Qian

来源：Neuropsychobiology, 2011, 64(2): 102-109.

DOI：10.1159/000324991

• Alzheimer's disease
• Apolipoprotein E epsilon 4
• Cognitive decline
• Nested case-control study

Background/Aims: Cognitive decline in the elderly is an early predictor of dementia. The apolipoprotein E (APOE) epsilon 4 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 epsilon 4 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 epsilon 4 frequency in the cognitive decline group was significantly higher than that in the stable group (p < 0.05), while the APOE epsilon 2 and epsilon 3 prevalence in the cognitive decline group did not differ significantly from that in controls ( p 1 0.05). At the first follow-up, modest but significant declines only in the memory domain were associated with APOE epsilon 4. At the last follow-up, significant associations were noted between APOE epsilon 4 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 epsilon 4 was significantly associated with the cognitive decline group, as compared to the stable group, adjusting for vascular diseases and lipid profile. Conclusions: APOE epsilon 4 offered information on the risk of cognitive decline in this longitudinal study, and may exert detectable effects early in a long prodromal AD trajectory.

• 出版日期2011
• 单位天津医科大学