Browsing by Author "Smeeth, Liam"

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    Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network
    (Wiley, 2022) 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.; Dominantly Inherited Alzheimer Network; Neurology, School of Medicine
    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.