Role of apolipoprotein ε4 allele as a predictor in the course and outcome in patients with subcortical vascular dementia

Abstract

AbstractBackgroundVascular dementia (VaD) is the second most common dementia in elderly and the major contributor being Cerebral Small Vessel Disease (SVD) which has radiological manifestations of White Matter Hyperintensities(WMH), Cerebral Microbleeds and Lacunar infarcts. This study looks into the role of clinico‐demographic profile, genetic factors in terms of Apo E4 status and neuropsychological characteristics in predicting the course and outcome in patients with Subcortical VaD.MethodA prospective cohort study involving 202 patients who were followed up at baseline and subsequently after 1 and 2 years’ time intervals following informed consent and IEC approval with attempt to understand the role of APOE4 positive status as a predictor for cognitive decline. Comparison of Neuropsychological test performance with ANOVA, regression analysis and survival analysis by plotting Kaplan Meier’s curve was done using SPSS v.21.ResultThe major risk factor identified was Hypertension in 92% followed by smoking in 76% and low socioeconomic status in 56% patients. 35.7% of the population had an APO E4 allele positivity. Regression analysis done showed APO E4 positive status as a significant independent predictor of poorer performance in neuropsychological test scores across time periods. However, survival analysis utilizing Kaplan Meir’s plot showed that unlike smoking and WMH (Odds ratio : 2.62) which increased mortality rates more than twofold, APO E4 did not contribute to increased mortality.ConclusionThis study comprehensively looks into the role of APO E4 in VaD and identifies need for prevention of modifiable risk factors like smoking, hypertension, low SES, poor cognitive reserves and WMH which predicts cognitive decline in subcortical VaD and lead to early mortality in patients with VaD. Positive APO E4 allele status significantly affects performance in cognitive assessments but does not appear to predict mortality and hence risk modification needs to be tailored in patients with VaD.