Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network
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- Department of Non‐Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine London United Kingdom
- Department of Medical Statistics London School of Hygiene and Tropical Medicine London United Kingdom
- Institute of Child Health University College London Gower Street London WC1E 6BT United Kingdom, Virology Department Great Ormond Street Hospital London United Kingdom
- Virology Department Great Ormond Street Hospital London United Kingdom
- Indiana University School of Medicine Indianapolis Indiana USA
- Department of Clinical Neuroscience Osaka Metropolitan University Medical School, Sutoku University Osaka Japan
- Department of Radiology Washington University School of Medicine in St Louis Missouri USA
- German Center for Neurodegenerative Diseases Site Munich Germany, Department of Neurology Ludwig‐Maximilians University Munich Germany
- Department of Neurology Washington University School of Medicine St. Louis USA
- Neuroscience Research Australia Sydney New South Wales Australia, School of Medical Sciences University of New South Wales Sydney New South Wales Australia
- Department of Neurology University of Ulsan College of Medicine, Asan Medical Center Seoul South Korea
- UK Dementia Research Institute University College London London United Kingdom, Dementia Research Centre, Institute of Neurology University College London Queen Square London United Kingdom
- Dementia Research Centre, Institute of Neurology University College London Queen Square London United Kingdom, NIHR University College London Hospitals Biomedical Research Centre London United Kingdom
Abstract Objective To investigate whether herpes simplex virus type 1 (HSV‐1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). Methods Among two subsets of the DIAN cohort (age range 19.6–66.6 years; median follow‐up 3.0 years) we examined (i) rate of cognitive decline ( N = 164) using change in mini‐mental state examination (MMSE) score, (ii) rate of whole brain atrophy ( N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV‐1 antibodies were assayed in baseline sera collected from 2009–2015. Linear mixed‐effects models were used to compare outcomes by HSV‐1 seropositivity and high HSV‐1 IgG titres/IgM status. Results There was no association between baseline HSV‐1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV‐1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope − 0.365, 95% CI: −0.958 to −0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV‐1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV‐1 seronegative. Among mutation‐negative individuals, no differences were seen by HSV‐1. Stratifying by APOE4 status yielded inconsistent results. Interpretation We found no evidence for a major role of HSV‐1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early‐onset AD.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 1890570
- Journal Information:
- Annals of Clinical and Translational Neurology, Journal Name: Annals of Clinical and Translational Neurology Journal Issue: 11 Vol. 9; ISSN 2328-9503
- Publisher:
- Wiley Blackwell (John Wiley & Sons)Copyright Statement
- Country of Publication:
- Country unknown/Code not available
- Language:
- English
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