| アブストラクト | 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. |
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| 投稿者 | Warren-Gash, Charlotte; Cadogan, Sharon L; Nicholas, Jennifer M; Breuer, Judith M; Shah, Divya; Pearce, Neil; Shiekh, Suhail; Smeeth, Liam; Farlow, Martin R; Mori, Hiroshi; Gordon, Brian A; Nuebling, Georg; McDade, Eric; Bateman, Randall J; Schofield, Peter R; Lee, Jae-Hong; Morris, John C; Cash, David M; Fox, Nick C; Ridha, Basil H; Rossor, Martin N |
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| 組織名 | 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.;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.;NIHR University College London Hospitals Biomedical Research Centre, London,;United Kingdom. |
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