Patients with gout may have smaller brain volumes and higher brain iron markers than people without gout, and also be more likely to develop Parkinson’s disease, probable essential tremor, and dementia, researchers in the United Kingdom report.
“We were surprised about the regions of the brain affected by gout, several of which are important for motor function. The other intriguing finding was that the risk of dementia amongst gout patients was strongly time-dependent: highest in the first 3 years after their gout diagnosis,” lead study author Anya Topiwala, BMBCh, DPhil, said in an interview.
Dr. Anya Topiwala
“Our combination of traditional and genetic approaches increases the confidence that gout is causing the brain findings,” said Dr. Topiwala, a clinical research fellow and consultant psychiatrist in the Nuffield Department of Population Health at the University of Oxford, England.
“We suggest that clinicians be vigilant for cognitive and motor problems after gout diagnosis, particularly in the early stages,” she added.
Links between gout and neurodegenerative diseases debated in earlier studies
Gout, the most common inflammatory arthritis, affects around 1%-4% of people, the authors wrote, with monosodium urate crystal deposits causing acute flares of pain and swelling in joints and periarticular tissues.
Whether and how gout may affect the brain has been debated in the literature. Gout and hyperuricemia have been linked with elevated stroke risk; and although observational studies have linked hyperuricemia with lower dementia risk, especially Alzheimer’s disease, Mendelian randomization studies have had conflicting results in Alzheimer’s disease.
A novel approach that analyzes brain structure and genetics
In a study published in Nature Communications, Dr. Topiwala and her colleagues combined observational and Mendelian randomization techniques to explore relationships between gout and neurodegenerative diseases. They analyzed data from over 303,000 volunteer participants between 40 and 69 years of age recruited between 2006 and 2010 to contribute their detailed genetic and health information to the U.K. Biobank, a large-scale biomedical database and research resource.
Patients with gout tended to be older and male. At baseline, all participants’ serum urate levels were measured, and 30.8% of patients with gout reported that they currently used urate-lowering therapy.
MRI shows brain changes in patients with gout
In what the authors said is the first investigation of neuroimaging markers in patients with gout, they compared differences in gray matter volumes found in the 1,165 participants with gout and the 32,202 controls without gout who had MRI data.
They found no marked sex differences in associations. Urate was inversely linked with global brain volume and with gray and white matter volumes, and gout appeared to age global gray matter by 2 years.
Patients with gout and higher urate showed significant differences in regional gray matter volumes, especially in the cerebellum, pons, and midbrain, as well as subcortical differences in the nucleus accumbens, putamen, and caudate. They also showed significant differences in white matter tract microstructure in the fornix.
Patients with gout were more likely to develop dementia (average hazard ratio [HR] over study = 1.60), especially in the first 3 years after gout diagnosis (HR = 7.40). They were also at higher risk for vascular dementia (average HR = 2.41), compared with all-cause dementia, but not for Alzheimer’s disease (average HR = 1.62).
In asymptomatic participants though, urate and dementia were inversely linked (HR = 0.85), with no time dependence.
Gout was linked with higher incidence of Parkinson’s disease (HR = 1.43) and probable essential tremor (HR = 6.75). In asymptomatic participants, urate and Parkinson’s disease (HR = 0.89), but not probable essential tremor, were inversely linked.