Association of gout with brain reserve and vulnerability to neurodegenerative disease

Topiwala, Anya; Mankia, Kulveer; Bell, Steven; Webb, Alastair; Ebmeier, Klaus P.; Howard, Isobel; Wang, Chaoyue; Alfaro-Almagro, Fidel; Miller, Karla L.; Burgess, Stephen; Smith, Stephen M.; Nichols, Thomas E.

doi:10.1038/s41467-023-38602-6

Cited by 13 publications

(6 citation statements)

References 58 publications

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“…Thereafter, 12 articles were thought to be eligible and assessed for full‐text review. Seven articles were excluded, and seven research articles were included in the final meta‐analysis (Hong et al., 2015; Kim et al., 2023; Latourte et al., 2018; Lu et al., 2016; Min et al., 2021; Scheepers et al., 2019; Topiwala et al., 2023).…”

Section: Resultsmentioning

confidence: 99%

Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta‐analysis based on latest evidence

Wang,

Tan,

Wang

et al. 2023

Brain and Behavior

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ObjectivePrevious studies have found the potential role of gout or hyperuricemia in subsequent development of Alzheimer's disease (AD) but reported inconsistent results. We conducted the current meta‐analysis to evaluate whether an association exists between gout/ hyperuricemia and AD.MethodsWe systematically searched PubMed and EMBASE for the published cohort studies that measured the risk of AD in subject with gout/ hyperuricemia up to May 20, 2023. Data extraction was employed by two authors independently. Rev Man 5.3 and Stata 15.0 software were used to calculate the relative ratio (RR) or hazard ratio (HR) for including studies. Subgroup analysis was performed to assess the sources of heterogeneity. A random‐effects model was adopted when heterogeneity was present. The funnel plot, Begg's test, and and Egger's test were used to assess publication bias.ResultsAfter rigorous screening, seven eligible studies were included in the final analyses. Pooled results indicated that gout or hyperuricemia decreases the risk of AD (RR: 0.69, 95% CI: 0.64∼0.72), with a high heterogeneity of 93%. Subgroup analyses showed that regional distribution was the source of heterogeneity. Egger's and Begg's tests as well as visual inspection of funnel plot suggested no publication bias in the studies.ConclusionThe findings suggested that gout or hyperuricemia might have a protective effect against AD. This negative correlation should be verified by more cohort studies due to the existence of substantial heterogeneity.

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Section: Resultsmentioning

confidence: 99%

Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta‐analysis based on latest evidence

Wang,

Tan,

Wang

et al. 2023

Brain and Behavior

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“…The presence of hyperuricemia is frequently associated with HBP, DM type 2, AF, and MetSy [30]. Recent data show an association between the increased occurrence of neurodegenerative diseases (dementia, essential tremor, and PD) in patients with hyperuricemia (especially by decreasing regional and global brain volumes) [31]. In our study, hyperuricemia was present in a higher proportion of Group 1 patients (p-value < 0.0001), which necessitated the more frequent use of allopurinol as a therapy to lower serum uric acid levels.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome: A Strange Companion of Atrial Fibrillation; A Blessing in Disguise from the Neuropsychiatric Point of View

et al. 2023

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Background: The concept of metabolic syndrome (MetSy) brings together components that individually represent a risk factor for cardiovascular diseases, which over time can prove to be more harmful if a combined effect of these is exhibited. Method: A single-centre retrospective study in an academic medical unit was conducted. We analysed the link between the MetSy and the occurrence of neuropsychic complications among atrial fibrillation (AF) patients. We sifted through the files of the patients admitted during 2015–2016 to the Municipal Emergency University Hospital Timisoara, Romania, with the diagnosis of AF. We divided these AF patients into two groups: the first group comprised patients with atrial fibrillation and MetSy (267 patients), while the second group comprised AF patients without MetSy (843 patients). We analysed the occurrence of neuropsychic changes (stroke, Parkinson’s disease, dementia, cognitive impairment, and silent lacunar infarction) among the two groups. Results: Cognitive impairment (p-value = 0.0081) and dementia (p-value < 0.0001) were less frequent in patients with AF and MetSy than in those with AF without MetSy. Regarding the presence of stroke and Parkinson’s disease (PD), we could not demonstrate the existence of any statistically significant difference between the two groups. Using logistic regression (enter test), we found that MetSy might have a protective effect (OR = 0.4040, 95% CI [0.2132; 0.7654], p-value = 0.0054) for the occurrence of dementia in those patients. Furthermore, obesity was the only factor with a possible protective effect from all the constituents of the MetSy when analysed together (with a significance level of p-value = 0.0004 for the logistic regression). The protective effect of MetSy against stroke occurrence was supplementarily proven by a longer period of survival without stroke from the AF diagnosis (3.521 years, p = 0.0304) compared to patients with AF without MetSy (3.286 years to first stroke occurrence). Conclusions: Metabolic syndrome might offer protection against the occurrence of dementia among patients with AF, but no effect was noted when compared with the presence of stroke. Further studies on larger cohorts can help us reach a conclusion regarding the positive effects of the metabolic syndrome.

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“…Gout arthritis is the most common inflammatory arthritis worldwide 1 , 2 . It is triggered by monosodium urate crystals (MSU) deposition in the joints 1 .…”

Section: Introductionmentioning

confidence: 99%

CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis

Yin,

Liu,

Dong

et al. 2024

Nat Commun

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Gouty arthritis evokes joint pain and inflammation. Mechanisms driving gout pain and inflammation remain incompletely understood. Here we show that CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to drive gout pain and inflammation. CXCL5 expression was increased in ankle joints of gout arthritis model mice, whereas CXCR2 showed expression in joint-innervating sensory neurons. CXCL5 activates CXCR2 expressed on nociceptive sensory neurons to trigger TRPA1 activation, resulting in hyperexcitability and pain. Neuronal CXCR2 coordinates with neutrophilic CXCR2 to contribute to CXCL5-induced neutrophil chemotaxis via triggering CGRP- and substance P-mediated vasodilation and plasma extravasation. Neuronal Cxcr2 deletion ameliorates joint pain, neutrophil infiltration and gait impairment in model mice. We confirmed CXCR2 expression in human dorsal root ganglion neurons and CXCL5 level upregulation in serum from male patients with gouty arthritis. Our study demonstrates CXCL5-neuronal CXCR2-TRPA1 axis contributes to gouty arthritis pain, neutrophil influx and inflammation that expands our knowledge of immunomodulation capability of nociceptive sensory neurons.

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Association of gout with brain reserve and vulnerability to neurodegenerative disease

Cited by 13 publications

References 58 publications

Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta‐analysis based on latest evidence

Gout/hyperuricemia reduces the risk of Alzheimer's disease: A meta‐analysis based on latest evidence

Metabolic Syndrome: A Strange Companion of Atrial Fibrillation; A Blessing in Disguise from the Neuropsychiatric Point of View

CXCL5 activates CXCR2 in nociceptive sensory neurons to drive joint pain and inflammation in experimental gouty arthritis

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