Oliveira Fabricio F, Chen Elizabeth S, Smith Marilia C, Bertolucci Paulo H F
Departments of *Neurology and Neurosurgery †Morphology and Genetics, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil.
Alzheimer Dis Assoc Disord. 2016 Jul-Sep;30(3):243-50. doi: 10.1097/WAD.0000000000000117.
Little is known on how risk factors for Alzheimer disease (AD) dementia affect disease progression, much less for populations with low mean schooling, whereas the transcription of APOE may be regulated by nongenetic factors. In this 44-month cohort study, 214 consecutive outpatients with late-onset AD were assessed for rates of cognitive and functional decline by way of Clinical Dementia Rating and Mini-Mental State Examination (MMSE) scores, keeping blinded assessment of APOE haplotypes. Subjects were evaluated for sex, schooling, age of dementia onset, and cerebrovascular risk factors (including Framingham risk scores). Of the 214 patients, there were 146 (68.2%) women and 113 (52.8%) APOE4+ carriers. The mean age of AD onset was 73.4±6.5 years-old, negatively correlated with time to Clinical Dementia Rating >1.0 (β=-0.132; ρ<0.001), MMSE=20 (β=-0.105; ρ<0.001), and MMSE=15 (β=-0.124; ρ=0.003), more significantly for women and APOE4+ carriers. Mean schooling was 4.18±3.7 years, correlated with time to MMSE=20 and MMSE=15 for women and APOE4+ carriers. Body mass index was correlated with time to MMSE=20 only for men (ρ=0.006). The 10-year coronary heart disease risk was correlated with time to MMSE=20 only for APOE4+ carriers (ρ=0.015). These outcomes suggest interactions among genomic effects of cognitive reserve, cerebral perfusion, and hormonal changes over mechanisms of neurodegeneration.
对于阿尔茨海默病(AD)痴呆的风险因素如何影响疾病进展,人们了解甚少,对于平均受教育程度较低的人群更是如此,而APOE的转录可能受非遗传因素调控。在这项为期44个月的队列研究中,对214例连续的晚发性AD门诊患者通过临床痴呆评定量表和简易精神状态检查表(MMSE)评分评估认知和功能衰退率,同时对APOE单倍型进行盲法评估。对受试者的性别、受教育程度、痴呆发病年龄和脑血管危险因素(包括弗雷明汉风险评分)进行评估。在214例患者中,有146例(68.2%)为女性,113例(52.8%)为APOE4+携带者。AD发病的平均年龄为73.4±6.5岁,与临床痴呆评定量表>1.0的时间呈负相关(β=-0.132;ρ<0.001),与MMSE=20呈负相关(β=-0.105;ρ<0.001),与MMSE=15呈负相关(β=-0.124;ρ=0.003),在女性和APOE4+携带者中更为显著。平均受教育年限为4.18±3.7年,与女性和APOE4+携带者达到MMSE=20和MMSE=15的时间相关。体重指数仅与男性达到MMSE=20的时间相关(ρ=0.006)。仅对于APOE4+携带者,10年冠心病风险与达到MMSE=20的时间相关(ρ=0.015)。这些结果表明认知储备、脑灌注和激素变化的基因组效应在神经退行性变机制上存在相互作用。