Herpes Simplex Virus, APOEɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study

Article type: Research Article

Authors: Lövheim, Hugo^{a; *} | Norman, Tove^a | Weidung, Bodil^{a; b} | Olsson, Jan^c | Josefsson, Maria^{d; e} | Adolfsson, Rolf^f | Nyberg, Lars^{e; g; h} | Elgh, Fredrik^c

Affiliations: [a] Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden | [b] Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden | [c] Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden | [d] Centre for Demographic and Ageing Research, Umeå University, Umeå, Sweden | [e] Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden | [f] Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden | [g] Department of Radiation Sciences, Umeå University, Umeå, Sweden | [h] Department of Integrative Medical Biology, Umeå University, Umeå, Sweden

Correspondence: [*] Correspondence to: Hugo Lövheim, Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, SE-901 85 Umeå, Sweden. Tel.: +46 90 785 88 59; E-mail: hugo.lovheim@umu.se.

Abstract: Background:Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer’s disease (AD) development. Objective:The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOE ɛ4) in a large population-based cohort with a long follow-up time. Methods:The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOE ɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared. Results:Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOE ɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOE ɛ4 for episodic memory decline (p < 0.001). Conclusion:In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOE ɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.

Keywords: Alzheimer’s disease, APOE ɛ4, apolipoprotein E4, cognitive impairment, cohort study, dementia, epidemiological study, episodic memory, herpes simplex virus

DOI: 10.3233/JAD-171162

Journal: Journal of Alzheimer's Disease, vol. 67, no. 1, pp. 211-220, 2019