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The ε4 allele of the apolipoprotein E (APOE) gene is the strongest genetic risk factor for late-onset Alzheimer's disease (AD)
.
Approximately 25% of Caucasians carry at least one ε4 allele.
In addition to AD, APOE ε4 also plays a role in other causes of dementia, including vascular dementia and Lewy body disease
.
Although case-control and longitudinal studies have studied the relationship between APOE and dementia, its relationship with cognitive decline during adult life is still controversial
Some studies have shown that identical twins of APOE ε4 accelerate cognitive decline, while fraternal twins do not
.
In addition, the relationship between APOE ε4 and cognition is thought to change with age; some but not all studies report that ε4 carriers have better cognitive performance when they are young
In order to solve these limitations, Amin Gharbi-Meliani of the French National Institute of Health and others have studied the relationship between homotypic and heterotypic APOE ε4 and cognitive decline and dementia from middle age to old age
.
They conducted a cohort study of 5561 participants (mean age 55.
5 (SD=5.
9) years old, 27.
1% were women).
During the average (SD) 20.
2 (2.
8) year follow-up period (Whitehall II study), they evaluated reasoning, memory, Semantic and phonemic fluency were tested repeatedly
.
And use the joint model to study the relationship between APOE genotype and the trajectory of cognitive function between the ages of 45 and 85.
They found that compared with non-carriers, heterozygous (prevalence 25%) and homozygous (prevalence 2%) APOE ε4 carriers had an increased risk of dementia, and the subdistributed hazard ratio was 2.
19 (95% CI 1.
73).
, 2.
77) and 5.
97 (95% CI 3.
85, 9.
28)
.
Using data spanning 45-85 years old, with non-ε4 carriers as a reference, ε4 homotypes have poor global cognitive scores from 65 years old; ε4 heterotypes have better scores between 45-55 years old, and then There is no difference, until after 75 years of age there is a poor cognitive score
.
In the analysis of a single cognitive test, young ε4 heterozygotes have better cognitive performance, mainly due to executive function
The important significance of this study is to find that heterozygous and homozygous carriers of APOE ε4 have poorer cognitive ability and greater risk of dementia in old age
.
APOE ε4 heterozygotes have complex antagonistic effects in the life of adults, which are characterized by cognitive advantages in middle age
Heterozygous and homozygous carriers of ε4 have poorer cognitive abilities and greater risk of dementia in old age
Original source:
Gharbi-Meliani A, Dugravot A, Sabia S, et al.
The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study.
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