Association Between Gout and Dementia in the Elderly: A Nationwide Population-Based Cohort Study

Min, Kyung Hyun; Kang, Sang Oh; Oh, Su Jin; Han, Ji Min; Lee, Jun Young

doi:10.1016/j.jagp.2021.01.016

Cited by 21 publications

(28 citation statements)

References 39 publications

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“…Two papers from Engel et al [ 10 ] and Min et al [ 12 ] only showed the effect of total urate-lowering agents. The study of Engel et al [ 10 ] addressed that allopurinol accounted for 98.4% of the total urate-lowering agents, but the individual OR and 95% CI for allopurinol use were not provided.…”

Section: Resultsmentioning

confidence: 99%

“…The study of Engel et al [ 10 ] addressed that allopurinol accounted for 98.4% of the total urate-lowering agents, but the individual OR and 95% CI for allopurinol use were not provided. The study of Min et al [ 12 ] addressed that there was no significant correlation between the use of allopurinol and the probability of dementia, but the OR and 95% CI were not shown. After excluding these 2 studies of Engel et al and Min et al, a pooled OR was 1.0 (95% CI = 0.87–1.14 and P = .99).…”

Section: Resultsmentioning

confidence: 99%

“…The other studies did not report the sex-specific estimates. [ 10 , 12 , 14 ] It points out the future research direction in sex. Fifth, due to the limitation of claims data used, the laboratory information was not available in the 4 eligible studies.…”

Section: Discussionmentioning

confidence: 99%

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Allopurinol use and the risk of dementia: A meta-analysis of case–control studies

Lai

Hwang

Kuo³

et al. 2022

Medicine

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Background. This study aimed to compare the risk of dementia between exposed to allopurinol and not exposed to allopurinol in persons who had gout and/or hyperuricemia. Methods. The meta-analysis was conducted to select case–control research written in English through the help of PubMed and Web of Science. The pooled odds ratio (OR) with 95% confidence interval based on the fixed-effect model was applied to compare the allopurinol exposure among cases (subjects with dementia) and controls (subjects without dementia). Results. A total of 4 case–control studies relating the allopurinol exposure to the risk of dementia were identified. The study duration was from 9 to 14 years. The number of study persons was from 3148 to 137,640. The male percentage of study subjects was from 36.9 to 62.5. The mean age of study persons was from 72.3 to 78.7 years. Overall, the odds of the allopurinol exposure among cases were lower than the odds of the allopurinol exposure among control subjects (OR = 0.91, 95% confidence interval = 0.87–0.95, P < .001). The heterogeneity between these eligible studies was low ( I² = 0%). The sensitivity analysis revealed that after excluding the studies with concern, the pooled OR did not achieve statistical significance. Conclusions. This is the first meta-analysis to report that there is a negative relationship between the allopurinol exposure and the risk of dementia. Although the results favor the hypothesis, currently it is unable to draw strong conclusions about the protective effect of allopurinol against dementia due to inclusion of only a few eligible studies. Randomized controlled trials are needed to explore the relationship between allopurinol exposure and the probability of dementia.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Allopurinol use and the risk of dementia: A meta-analysis of case–control studies

Lai

Hwang

Kuo³

et al. 2022

Medicine

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“…FBX administration suppresses the phenotype of tauopathies. XO/XDH inhibitors have been reported to suppress the onset of dementia 24 , 34 . The effect of FBX was tested using transgenic animals expressing Tau (WT4R) in the nerve (tmIs390 [Punc-119::WT4R, Pges-1::EGFP]) as a model for Alzheimer's disease, which is said to account for approximately 70% of dementia.…”

Section: Resultsmentioning

confidence: 99%

“…Mitochondrial or bioenergetic dysfunction may be related to the etiology of Alzheimer's disease (AD) and Parkinson's disease (PD). Additionally, gout patients treated with UA-lowering drugs have a lower risk of both vascular and nonvascular dementia 34 . Furthermore, impaired removal of defective mitochondria is a pivotal event in AD pathogenesis, suggesting that targeting the maintenance of mitochondrial quality may be a promising therapeutic strategy 37 .…”

Section: Discussionmentioning

confidence: 99%

Regulation of aging by balancing mitochondrial function and antioxidant levels.

Yoshina

Izuhara

Kamatani³

et al. 2022

Preprint

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Aging is the deterioration of physiological mechanisms that is associated with getting old. There is a link between aging and mitochondrial function. In C. elegans, it has been reported that inhibiting the electron transfer system decreases ATP production and extends lifespan. However, it has also been suggested that energy loss due to mitochondrial dysfunction or impairment is a mechanism of diseases and aging. Thus, there is an unresolved relationship between ATP levels and aging. To address this issue, we administered febuxostat (FBX), an inhibitor of human xanthine oxidase (XO)/xanthine dehydrogenase (XDH), to C. elegans. XO/XDH is an enzyme that participates in the in vivo synthesis of uric acid. When FBX is added to cells, the salvage pathway of purine metabolism becomes dominant, and the ATP concentration increases. Since humans and C. elegans but few mammalian species lack uricase, which degrades uric acid, we used C. elegans as a model to evaluate the effects of FBX and to challenge the enigma of the relationship between ATP and lifespan.In this study, we showed that FBX protects mitochondria and prevents age-related muscle deterioration in C. elegans. In addition, we showed that FBX administration could increase ATP levels without overloading the mitochondria while extending the lifespan. We also showed that the combination of FBX and an antioxidant as a protection against ROS prolongs lifespan more. We have shown that the antioxidant effects and increased ATP levels may lead to antiaging effects.

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Impact of Clinical Association Between Gout and Dementia: A Nationwide Population‐Based Cohort Study in Korea

Kim

Yim

Choi

et al. 2022

Arthritis Care & Research

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Objective. Hyperuricemia might have neuroprotective or neurodegenerative effects on dementia via oxidative stress or inflammatory response regulation. Few studies have explored the association of hyperuricemia or gout with dementia. This retrospective cohort study aimed to investigate the association between gout and dementia in Korea.Methods. Altogether, 5,052 gout patients and 25,260 age-and sex-matched controls were selected from the National Health Insurance Service (NHIS)-National Sample Cohort database. The incidence and risk of dementia were evaluated by reviewing the NHIS record. We also performed a subgroup analysis according to age group (age <65 or ≥65 years) using the standard age of 65 years for elderly and nonelderly groups and sex.Results. During follow-up, 81 and 558 participants in the gout and control cohorts developed dementia, respectively. The mean follow-up duration was 4.38 years in gout patients and 4.94 years in controls. Gout patients had a hazard ratio (HR) of 0.79 for overall dementia (95% confidence interval [95% CI] 0.62-1.00) and significantly lower Alzheimer's disease risk (HR 0.73 [95% CI 0.54-0.98]) after adjusting for age, sex, household income, and comorbidities. In subgroup analysis stratified by age and sex, the inverse association between gout and the risk of overall dementia (HR 0.71 [95% CI 0.52-0.97]) and Alzheimer's disease (HR 0.67 [95% CI 0.46-0.97]) were observed in the elderly male group. On the other hand, age-and sex-adjusted analysis showed that the HR for vascular dementia of gout patients was 2.31 (95% CI 1.02-5.25) in the nonelderly male group.Conclusion. Gout decreased the risk of incident Alzheimer's disease-type dementia, especially in elderly patients. The association between gout and dementia risk may differ according to age and disease duration.

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Association Between Gout and Dementia in the Elderly: A Nationwide Population-Based Cohort Study

Cited by 21 publications

References 39 publications

Allopurinol use and the risk of dementia: A meta-analysis of case–control studies

Allopurinol use and the risk of dementia: A meta-analysis of case–control studies

Regulation of aging by balancing mitochondrial function and antioxidant levels.

Impact of Clinical Association Between Gout and Dementia: A Nationwide Population‐Based Cohort Study in Korea

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