Background:
Approximately 40 independent Single Nucleotide Polymorphisms (SNPs) have
been associated with Alzheimer’s Disease (AD) or cognitive decline in genome-wide association studies.
Methods:
We aimed to evaluate the joint effect of genetic polymorphisms and environmental factors on
the progression from Mild Cognitive Impairment (MCI) to AD (MCI-AD progression) in a Chinese
community cohort.
Conclusion:
Demographic, DNA and incident AD diagnosis data were derived from the follow-up of 316
participants with MCI at baseline of the Shanghai Aging Study. The associations of 40 SNPs and environmental
predictors with MCI-AD progression were assessed using the Kaplan-Meier method with the
log-rank test and Cox regression model.
Results:
Rs4147929 at ATP-binding cassette family A member 7 (ABCA7) (AG/AA vs. GG, hazard ratio
[HR] = 2.43, 95% confidence interval [CI] 1.24-4.76) and body mass index (BMI) (overweight vs.
non-overweight, HR = 0.41, 95% CI 0.22-0.78) were independent predictors of MCI-AD progression. In
the combined analyses, MCI participants with the copresence of non-overweight BMI and the ABCA7
rs4147929 (AG/AA) risk genotype had an approximately 6-fold higher risk of MCI-AD progression
than those with an overweight BMI and a non-risk genotype (HR = 6.77, 95% CI 2.60-17.63). However,
a nonsignificant result was found when participants carried only one of these two risk factors (nonoverweight
BMI and AG/AA of ABCA7 rs4147929).
Conclusion:
ABCA7 rs4147929 and BMI jointly affect MCI-AD progression. MCI participants with the
rs4147929 risk genotype may benefit from maintaining an overweight BMI level with regard to their
risk for incident AD.
Body Mass Index in Mild Cognitive Impairment According to Age, Sex, Cognitive Intervention, and Hypertension and Risk of Progression to Alzheimer's Disease
