Hugo Lövheim1, Tove Norman1, Bodil Weidung1,2, Jan Olsson3, Maria Josefsson4,5, Rolf Adolfsson6, Lars Nyberg5,7,8, Fredrik Elgh3. 1. Department of Community Medicine and Rehabilitation, Geriatric Medicine, Umeå University, Umeå, Sweden. 2. Department of Public Health and Caring Sciences, Geriatric Medicine, Uppsala University, Uppsala, Sweden. 3. Department of Clinical Microbiology, Virology, Umeå University, Umeå, Sweden. 4. Centre for Demographic and Ageing Research, Umeå University, Umeå, Sweden. 5. Umeå Center for Functional Brain Imaging, Umeå University, Umeå, Sweden. 6. Department of Clinical Sciences, Psychiatry, Umeå University, Umeå, Sweden. 7. Department of Radiation Sciences, Umeå University, Umeå, Sweden. 8. Department of Integrative Medical Biology, Umeå University, Umeå, Sweden.
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 (APOEɛ4) 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, APOEɛ4 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 APOEɛ4 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 APOEɛ4 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 APOEɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.
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 (APOEɛ4) 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, APOEɛ4 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 APOEɛ4 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 APOEɛ4 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 APOEɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.
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