title: Apolipoprotein ɛ4 is Associated with Dementia and Cognitive Impairment Predominantly Due to Alzheimer's Disease and Not with Vascular Cognitive Impairment: A Singapore-Based Cohort.
abstract: OBJECTIVE
  While the association for apolipoprotein ɛ4 allele (APOE4) with Alzheimer's disease (AD) has been consistently confirmed, the association with vascular cognitive impairment (VCI) is unclear. We therefore explored the relationship of APOE with both AD and cerebrovascular disease (CeVD) by examining the prevalence of APOE4 in AD, AD with CeVD and vascular dementia (VaD), as well as in cognitive impairment no dementia (CIND) with and without CeVD.
  
  
  METHODS
  We performed a case-control study with subjects recruited from memory clinics and the community. All subjects underwent standardized brain neuroimaging, clinical and neuropsychological assessments, following which they were classified using research criteria.
  
  
  RESULTS
  A total of 411 subjects; 92 controls with no cognitive impairment (NCI), 77 CIND without CeVD, 87 CIND with CeVD, 55 AD without CeVD, 68 AD with CeVD, and 32 VaD patients were recruited. Compared to NCI (16.3%), the prevalence of APOE4 carriers was significantly higher only in CIND (37.7%) and AD in the absence of CeVD (45.5%), but not in the three subgroups of VCI, namely CIND with CeVD (20.7%), AD with CeVD (27.9%) and VaD (25.0%). Logistic regression analyses also showed that APOE4 carriers were more likely to have CIND without CeVD (Odds Ratio [OR]: 3.34; 95% Confidence Interval [CI]: 1.59-7.03) and AD without CeVD (OR: 7.21; 95% CI: 2.74-18.98), but no such association was observed in the VCI subgroups.
  
  
  CONCLUSIONS
  APOE4 is significantly associated with dementia and CIND due to AD pathology, but not with VCI.
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yuek Ling
authors.initials: YL
authors.lastname: Chai
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Hazel Kai-Hui
authors.initials: HK
authors.lastname: Yeo
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Jiehao
authors.initials: J
authors.lastname: Wang
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Saima
authors.initials: S
authors.lastname: Hilal
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Singapore Eye Research Institute, Singapore National Eye Center, Singapore.|Duke-NUS Graduate Medical School, National University of Singapore, Singapore.|Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Mohammad Kamran
authors.initials: MK
authors.lastname: Ikram
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Raffles Neuroscience Centre, Raffles Hospital, Singapore.
authors.forename: Narayanaswamy
authors.initials: N
authors.lastname: Venketasubramanian
authors.affiliation: Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Boon-Seng
authors.initials: BS
authors.lastname: Wong
authors.affiliation: Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore.|Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Christopher Li-Hsian
authors.initials: CL
authors.lastname: Chen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000150:complications* / Q000000981:diagnostic imaging; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000235:genetics*; D015331:Cohort Studies; D003704:Dementia / Q000209:etiology* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D059906:Neuroimaging; D009483:Neuropsychological Tests; D011569:Psychiatric Status Rating Scales; D012846:Singapore; D014652:Vascular Diseases / Q000150:complications
chemical_list: D053327:Apolipoprotein E4
keywords: Alzheimer’s disease; apolipoprotein ɛ4; cerebrovascular disease; cognitive impairment no dementia; vascular cognitive impairment; vascular dementia