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Studies of the relationship between Alzheimer's disease (AD) and single nucleotide polymorphism (SNP) T/C in intron 2 of the cholesterol-24S-hydroxylase gene ( CYP46A1) have reported inconsistent results. To confirm the association between the CYP46A1 T/C polymorphism and AD risk, a meta-analysis containing 4,875 AD cases and 4,874 controls from 21 case-control studies was performed. There were 16 studies involving Europeans, four studies with Asians and one study with Africans. The combined results of overall analysis showed that the CYP46A1 T/C polymorphism increased the risk of AD significantly in recessive model [CC versus CT + TT, odds ratio (OR) = 1.20, 95 % confidence interval (CI) = 1.04-1.38, p = 0.01]. On subgroup analysis by ethnicity, similarly significant differences in recessive model were also found in Europeans. Another analysis of the synergistic effect of the CYP46A1 T/C polymorphism and the ε4 allele of the apolipoprotein E gene ( APOE ε4) was performed in eight studies with available stratified information. The results revealed that the presence of APOE ε4 allele could strengthen the effect of CC genotype on AD risk, and the reverse was also true. In conclusion, our meta-analysis has successfully proved that CC genotype of the CYP46A1 T/C polymorphism could increase the risk of AD, and this effect would be weakened in APOE ε4 non-carriers and strengthened in APOE ε4 carriers. [ABSTRACT FROM AUTHOR]

Mild cognitive impairment (MCI) is considered as the early stage of dementia which currently has no effective treatments. Reducing progression of cognitive decline at the MCI stage could be an important strategy for preventing conversion to dementia. The goal of this work was to screen for clinical predictors indicating the prognosis of MCI comprehensively; therefor, we assumed vascular risk factors (VRFs), carotid stenosis, and white matter changes (WMC) to be independent predictors. A total of 257 patients with MCI underwent collection of VRF information, neuropsychological evaluation, computed tomography angiography (CTA) to investigate carotid stenosis, and magnetic resonance imaging (MRI) to identify severity of WMC. After a 3-year follow-up period, the neuropsychological evaluation, CTA, and MRI were repeated to assess the progression of cognitive decline, carotid stenosis, and WMC. The conversion rate from MCI to dementia was 11.65% per year, and the conversion rate from MCI to Alzheimer's disease was 7.05% per year in our cohort. Cognitive decline (in terms of changes in Mini Mental State Examination scores) was associated with diabetes mellitus ( p = 0.004), baseline WMC severity ( p < 0.001), baseline carotid stenosis ( p < 0.001), and WMC severity change ( p < 0.001). Besides, diabetes, baseline WMC severity, baseline moderate-to-severe carotid stenosis, and carotid stenosis change during follow-up were predictors of conversion from MCI to dementia. Given the potential clinical predictors, our findings could imply that controlling blood glucose, removing carotid stenosis, and improving cerebral perfusion could be effective measures to delay cognitive decline in patients with MCI and prevent conversion from MCI to dementia. [ABSTRACT FROM AUTHOR]

Studies of the relationship between Alzheimer's disease (AD) and single nucleotide polymorphism (SNP) T/C in intron 2 of the cholesterol-24S-hydroxylase gene (CYP46A1) have reported inconsistent results. To confirm the association between the CYP46A1 T/C polymorphism and AD risk, a meta-analysis containing 4,875 AD cases and 4,874 controls from 21 case-control studies was performed. There were 16 studies involving Europeans, four studies with Asians and one study with Africans. The combined results of overall analysis showed that the CYP46A1 T/C polymorphism increased the risk of AD significantly in recessive model [CC versus CT + TT, odds ratio (OR) = 1.20, 95 % confidence interval (CI) = 1.04-1.38, p = 0.01]. On subgroup analysis by ethnicity, similarly significant differences in recessive model were also found in Europeans. Another analysis of the synergistic effect of the CYP46A1 T/C polymorphism and the ε4 allele of the apolipoprotein E gene (APOE ε4) was performed in eight studies with available stratified information. The results revealed that the presence of APOE ε4 allele could strengthen the effect of CC genotype on AD risk, and the reverse was also true. In conclusion, our meta-analysis has successfully proved that CC genotype of the CYP46A1 T/C polymorphism could increase the risk of AD, and this effect would be weakened in APOE ε4 non-carriers and strengthened in APOE ε4 carriers.