Association of Gout with Brain Reserve and Vulnerability to Neurodegenerative Disease
Association of Gout with Brain Reserve and Vulnerability to Neurodegenerative Disease
Abstract ObjectivTo assess the associations between gout, brain structure, and neurodegenerative disease incidence. MethodsUsing observational and Mendelian randomization analyses we investigated causal relationships between gout and brain health. Exposures included gout diagnosis (from self-report, linked health records and death records) and genetically proxied gout and serum urate. Outcomes were neuroimaging markers of brain structure and neurodegenerative disease incidence (ascertained through self-report, health records and death reports). Cox proportional hazards models were used to examine time to neurodegenerative disease diagnosis. Results11,735 UK Biobank participants (mean age 55.5±8.0 years and 50.5% female) had a diagnosis of gout (n=1165 in MRI subset). Dementia was ascertained in 3126 individuals over a mean follow-up time of 12.4±1.9 years. Gout patients had smaller global and regional brain volumes and higher brain iron markers. Genetic associations mirrored observational associations. Genetically proxied gout associated with lower global grey matter volume (beta= -0.05[-0.08 to -0.01]). Participants with gout had higher incidence of all-cause dementia (hazard ratio (HR)=1.60, 95% confidence interval (CI) [1.38-1.85]), Parkinson’s disease (HR=1.43[1.15 to 1.79]), and probable essential tremor (HR=6.75[5.69 to 8.00]). Risks were strongly time dependent, whereby associations with incident dementia were highest in the first 3 years after gout diagnosis (HR=7.40[4.95 to 11.07]). ConclusionsThese 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. Key pointsWhat is already known on this topic?Studies of neurodegenerative disease risk in gout are contradictory.Relationships with neuroimaging markers of brain structure, which may offer insights, are uncertain.What this study adds?In this prospective cohort study gout was associated with smaller brain volumes and higher incidence of multiple neurodegenerative diseases.Mendelian randomization analyses suggested gout is causally related to brain structure.How might this study affect research, practice or policy?Our findings emphasise the importance for clinicians of assessing for motor and cognitive impairments amongst gout patients, particularly in early years after diagnosis.
Mankia Kulveer、Bell Steven、Topiwala Anya、Webb Alastair、Howard Isobel、Burgess Stephen、Smith Stephen、Miller Karla、Ebmeier Klaus P、Wang Chaoyue、Alfaro-Almagro Fidel、Nichols Thomas E
Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds and NIHR Leeds Biomedical Research Centre, Chapel Allerton HospitalDepartment of Clinical Neurosciences, School of Clinical Medicine, University of CambridgeNuffield Department of Population Health, Big Data Institute, University of OxfordWolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of OxfordNuffield Department of Population Health, Big Data Institute, University of OxfordMRC Biostatistics Unit, School of Clinical Medicine, University of Cambridge||Department of Public Health and Primary Care, School of Clinical Medicine, University of CambridgeWellcome Centre for Integrative Neuroimaging (WIN FMRIB), Nuffield Department of Clinical Neurosciences, University of OxfordWellcome Centre for Integrative Neuroimaging (WIN FMRIB), Nuffield Department of Clinical Neurosciences, University of OxfordDepartment of Psychiatry, University of Oxford, Warneford HospitalWellcome Centre for Integrative Neuroimaging (WIN FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford||SJTU-Ruijin-UIH Institute for Medical Imaging TechnologyWellcome Centre for Integrative Neuroimaging (WIN FMRIB), Nuffield Department of Clinical Neurosciences, University of OxfordNuffield Department of Population Health, Big Data Institute, University of Oxford||Wellcome Centre for Integrative Neuroimaging (WIN FMRIB), Nuffield Department of Clinical Neurosciences, University of Oxford
神经病学、精神病学内科学医学研究方法
Mankia Kulveer,Bell Steven,Topiwala Anya,Webb Alastair,Howard Isobel,Burgess Stephen,Smith Stephen,Miller Karla,Ebmeier Klaus P,Wang Chaoyue,Alfaro-Almagro Fidel,Nichols Thomas E.Association of Gout with Brain Reserve and Vulnerability to Neurodegenerative Disease[EB/OL].(2025-03-28)[2025-08-02].https://www.medrxiv.org/content/10.1101/2022.11.09.22282119.点此复制
评论