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

Article type: Research Article

Authors: Chai, Yuek Ling^{a; b; 1} | Yeo, Hazel Kai-Hui^{c; 1} | Wang, Jiehao^c | Hilal, Saima^{a; b} | Ikram, Mohammad Kamran^{a; b; d; e; f} | Venketasubramanian, Narayanaswamy^{a; g} | Wong, Boon-Seng^{c; *} | Chen, Christopher Li-Hsian^{a; b}

Affiliations: [a] Memory Ageing and Cognition Centre (MACC), National University Health System, Singapore | [b] Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [c] Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore | [d] Singapore Eye Research Institute, Singapore National Eye Center, Singapore | [e] Duke-NUS Graduate Medical School, National University of Singapore, Singapore | [f] Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands | [g] Raffles Neuroscience Centre, Raffles Hospital, Singapore

Correspondence: [*] Correspondence to: Dr. Boon-Seng Wong, Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, MD9 Level 4, 2 Medical Drive, Singapore 117597, Singapore Tel.: +65 65167617; Fax: +65 67773271; Email: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Background and 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. Conclusion:APOE4 is significantly associated with dementia and CIND due to AD pathology, but not with VCI.

Keywords: Alzheimer’s disease, apolipoprotein ɛ4, cerebrovascular disease, cognitive impairment no dementia, vascular cognitive impairment, vascular dementia

DOI: 10.3233/JAD-150902

Journal: Journal of Alzheimer's Disease, vol. 51, no. 4, pp. 1111-1118, 2016