Association of gout with brain reserve and vulnerability to neurodegenerative disease
jats:titleAbstract</jats:title>jats:pStudies of neurodegenerative disease risk in gout are contradictory. Relationships with neuroimaging markers of brain structure, which may offer insights, are uncertain. Here we investigated associations between gout, brain structure, and neurodegenerative disease incidence. Gout patients had smaller global and regional brain volumes and markers of higher brain iron, using both observational and genetic approaches. Participants with gout also had higher incidence of all-cause dementia, Parkinson’s disease, and probable essential tremor. Risks were strongly time dependent, whereby associations with incident dementia were highest in the first 3 years after gout diagnosis. These findings suggest gout is causally related to several measures of brain structure. Lower brain reserve amongst gout patients may explain their higher vulnerability to multiple neurodegenerative diseases. Motor and cognitive impairments may affect gout patients, particularly in early years after diagnosis.</jats:p>
Acknowledgements: We wish to thank Maria Christodoulou and the University of Oxford Statistics Consulting service for providing advice on the survival model analyses. We also thank the Wellcome Trust—216462/Z/19/Z (A.T.), 225790/Z/22/Z (S.Bu.), 206589/Z/17/Z (A.W.), 215573/Z/19/Z (S.S.), 202788/Z/16/Z (K.Mi.), 100309/Z/12/Z (T.N.); the UK MRC—G1001354 (K.P.E.), G1001354 (K.P.E.); the European Commission—Horizon 2020 732592 (K.P.E.); the British Heart Foundation—RG/16/4/32218 (S.Be.); the NIH—R01EB026859 (T.N.); EPSRC—EP/S02428X/1 (I.H.); and the NIHR—BRC-1215-20014 (S.Be.); NIHR203312 (S.Bu.); BRC-1215-20014 (T.N.). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Funder: NIH R01EB02685 the National Institute for Health Research Oxford Biomedical Research Centre (BRC-1215-20014) Li Ka Shing Centre for Health Information and Discovery