Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network
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 ye...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-11-01
|
| Series: | Annals of Clinical and Translational Neurology |
| Online Access: | https://doi.org/10.1002/acn3.51669 |
| _version_ | 1811330150574325760 |
|---|---|
| author | Charlotte Warren‐Gash Sharon L. Cadogan Jennifer M. Nicholas Judith M. Breuer Divya Shah Neil Pearce Suhail Shiekh Liam Smeeth Martin R. Farlow Hiroshi Mori Brian A. Gordon Georg Nuebling Eric McDade Randall J. Bateman Peter R. Schofield Jae‐Hong Lee John C. Morris David M. Cash Nick C. Fox Basil H. Ridha Martin N. Rossor for the Dominantly Inherited Alzheimer Network |
| author_facet | Charlotte Warren‐Gash Sharon L. Cadogan Jennifer M. Nicholas Judith M. Breuer Divya Shah Neil Pearce Suhail Shiekh Liam Smeeth Martin R. Farlow Hiroshi Mori Brian A. Gordon Georg Nuebling Eric McDade Randall J. Bateman Peter R. Schofield Jae‐Hong Lee John C. Morris David M. Cash Nick C. Fox Basil H. Ridha Martin N. Rossor for the Dominantly Inherited Alzheimer Network |
| author_sort | Charlotte Warren‐Gash |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T15:56:15Z |
| format | Article |
| id | doaj.art-6365c17a3e4a4713927eeb6fdeb7543a |
| institution | Directory Open Access Journal |
| issn | 2328-9503 |
| language | English |
| last_indexed | 2024-04-13T15:56:15Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Annals of Clinical and Translational Neurology |
| spelling | doaj.art-6365c17a3e4a4713927eeb6fdeb7543a2022-12-22T02:40:40ZengWileyAnnals of Clinical and Translational Neurology2328-95032022-11-019111727173810.1002/acn3.51669Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer NetworkCharlotte Warren‐Gash0Sharon L. Cadogan1Jennifer M. Nicholas2Judith M. Breuer3Divya Shah4Neil Pearce5Suhail Shiekh6Liam Smeeth7Martin R. Farlow8Hiroshi Mori9Brian A. Gordon10Georg Nuebling11Eric McDade12Randall J. Bateman13Peter R. Schofield14Jae‐Hong Lee15John C. Morris16David M. Cash17Nick C. Fox18Basil H. Ridha19Martin N. Rossor20for the Dominantly Inherited Alzheimer NetworkDepartment of Non‐Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine London United KingdomDepartment of Non‐Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine London United KingdomDepartment of Medical Statistics London School of Hygiene and Tropical Medicine London United KingdomInstitute of Child Health University College London Gower Street London WC1E 6BT United KingdomVirology Department Great Ormond Street Hospital London United KingdomDepartment of Medical Statistics London School of Hygiene and Tropical Medicine London United KingdomDepartment of Non‐Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine London United KingdomDepartment of Non‐Communicable Disease Epidemiology London School of Hygiene and Tropical Medicine London United KingdomIndiana University School of Medicine Indianapolis Indiana USADepartment of Clinical Neuroscience Osaka Metropolitan University Medical School, Sutoku University Osaka JapanDepartment of Radiology Washington University School of Medicine in St Louis Missouri USAGerman Center for Neurodegenerative Diseases Site Munich GermanyDepartment of Neurology Washington University School of Medicine St. Louis USADepartment of Neurology Washington University School of Medicine St. Louis USANeuroscience Research Australia Sydney New South Wales AustraliaDepartment of Neurology University of Ulsan College of Medicine, Asan Medical Center Seoul South KoreaDepartment of Neurology Washington University School of Medicine St. Louis USAUK Dementia Research Institute University College London London United KingdomDementia Research Centre, Institute of Neurology University College London Queen Square London United KingdomDementia Research Centre, Institute of Neurology University College London Queen Square London United KingdomDementia Research Centre, Institute of Neurology University College London Queen Square London United KingdomAbstract 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.https://doi.org/10.1002/acn3.51669 |
| spellingShingle | Charlotte Warren‐Gash Sharon L. Cadogan Jennifer M. Nicholas Judith M. Breuer Divya Shah Neil Pearce Suhail Shiekh Liam Smeeth Martin R. Farlow Hiroshi Mori Brian A. Gordon Georg Nuebling Eric McDade Randall J. Bateman Peter R. Schofield Jae‐Hong Lee John C. Morris David M. Cash Nick C. Fox Basil H. Ridha Martin N. Rossor for the Dominantly Inherited Alzheimer Network Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network Annals of Clinical and Translational Neurology |
| title | Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network |
| title_full | Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network |
| title_fullStr | Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network |
| title_full_unstemmed | Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network |
| title_short | Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network |
| title_sort | herpes simplex virus and rates of cognitive decline or whole brain atrophy in the dominantly inherited alzheimer network |
| url | https://doi.org/10.1002/acn3.51669 |
| work_keys_str_mv | AT charlottewarrengash herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT sharonlcadogan herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT jennifermnicholas herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT judithmbreuer herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT divyashah herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT neilpearce herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT suhailshiekh herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT liamsmeeth herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT martinrfarlow herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT hiroshimori herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT brianagordon herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT georgnuebling herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT ericmcdade herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT randalljbateman herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT peterrschofield herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT jaehonglee herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT johncmorris herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT davidmcash herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT nickcfox herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT basilhridha herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT martinnrossor herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork AT forthedominantlyinheritedalzheimernetwork herpessimplexvirusandratesofcognitivedeclineorwholebrainatrophyinthedominantlyinheritedalzheimernetwork |