In a recent study published within the journal Nature Communications, researchers explore the connection between gout and neurodegenerative disease susceptibility.

Study: Association of gout with brain reserve and vulnerability to neurodegenerative disease. Image Credit: Triff / Shutterstock.com

What’s gout?

Gout, which is sometimes called hyperuricemia, is essentially the most prevalent type of inflammatory arthritis, because it affects between 1% and 4% of the population. Gout is the results of monosodium urate crystal deposition within the joints and peri-articular tissues, which subsequently results in an inflammatory response, swelling, and pain.

Recent studies have made conflicting observations regarding the connection between gout and neurodegenerative diseases. For instance, some observational studies have reported that gout is related to a reduced risk of dementia, especially Alzheimer’s disease, whereas Mendelian randomization studies haven’t confirmed these findings. A history of gout has also been shown to extend the danger of stroke.  

These contradictory findings emphasize the necessity for more studies, particularly those involving brain structure evaluation, to higher understand the connection between gout and neurodegenerative diseases.

In regards to the study

Study participants were recruited from the UK Biobank (UKB) study, which enrolled 40 to 69-year-old volunteers between 2006 and 2010. A subset of those patients underwent imaging, including magnetic resonance imaging (MRI) of the brain.

Diagnostic criteria for gout were derived algorithmically from UKB baseline assessment information collection. All participants’ serum urate levels were estimated at the start of the study.

The team utilized 2,138 summary image-derived phenotypes (IDPs) that represented different estimates of brain structure using T1-weighted and T2-weighted-FLAIR structural imaging, diffusion MRI, and susceptibility-weighted MRI. FMRIB software library voxel-based morphometry (FSL-VBM) was used to find out the precise spatial distribution of relationships between gout and grey matter volume throughout the brain.

MRI results were used to find out whether causal relationships could explain the observed associations with brain structure. One-sample (gout) and two-sample (urate) linear MRI assessments utilizing summary statistics obtained from European participants were also performed.

Variant harmonization guaranteed that the correlation between single nucleotide polymorphisms (SNPs) and exposures, in addition to SNPs and outcomes, described the identical allele. Several robust MRI techniques were employed to guage the consistency of every causal inference.

Gout increases the danger of dementia and Parkinson’s

A complete of 11,735 participants with gout were included in the present study, 1,165 of whom underwent brain imaging. About 31% of all gout patients were currently being treated with urate-lowering therapy (ULT).

A lot of the patients with gout were older and males. Notably, urate levels in male gout patients were positively correlated with alcohol intake and lower socioeconomic status.  

In the course of the follow-up period, 3,126 participants reported dementia, and 16,422 died, with gout patients twice as more likely to die as in comparison with controls.

Urate levels were inversely related to global brain, grey matter, white matter, and high cerebrospinal fluid volumes. In truth, gout was found to exert the identical impact on global grey matter volume as that which is observed when comparing the brain scans of a healthy individual to those of a person who’s two years older.

A few of the specific gray matter regions of the brain that were affected by gout included the cerebellum, pons, and midbrain. Likewise, white matter regions, including the fornix, exhibited higher mean diffusivity and lower fractional anisotropy in gout patients.

A history of gout and high urate serum levels were also related to a greater degree of iron deposition within the bilateral putamen and caudate, each of that are basal ganglia structures. High iron levels inside these brain structures could also be as a result of gout-related inflammatory processes or poor urinary iron excretion, as controlling for renal function was found to cut back this association.

Gout was positively related to dementia, particularly vascular dementia, with the very best risk of a dementia diagnosis occurring in the primary three years following a gout diagnosis. Moreover, gout increases the danger of each Parkinson’s disease and probable essential tremors.

Conclusions

The present study is the primary of its kind to correlate neuroimaging studies with gout, with its findings providing evidence for a causal involvement of gout in dementia and other neurodegenerative disease. Nevertheless, the researchers didn’t observe any classical imaging markers of Alzheimer’s disease or vascular dementia within the brains of gout patients.  

Taken together, the study findings are essential for clinicians treating gout patients, as prophylactic treatments for gout may additionally reduce the danger of those patients developing neurodegenerative disorders in the long run. These observations may additionally provide latest insights into the various pathways involved within the pathogenesis of neurodegenerative diseases that could be used to discover novel therapeutic targets.