allopurinol and Dementia

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.. 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).. 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.. 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.

Topics: Aged; Allopurinol; Case-Control Studies; Dementia; Gout; Gout Suppressants; Humans; Male

Aggressive behaviour is commonly observed in patients with dementia, and current pharmacological treatments are still deficient in terms of efficacy and tolerability. Allopurinol is an inhibitor of the enzyme xanthine oxidase, with previously suggested anti-aggressive effects. After successful treatment of aggression in two patients, we performed a case-series study with allopurinol 300 mg a day orally for 6 weeks (increasing 300 mg every 2 weeks if the response was less than 50%) in six patients with dementia associated with prominent aggressive behaviour who failed to respond to two previous treatment strategies. Five patients were considerably responsive to allopurinol (four with 300 mg within 2 weeks and one with 600 mg), apparently without side-effects, which is in accordance with its well-established safety and tolerability profile. The observed therapeutic effect of allopurinol might be due to the inhibition of the enzyme xanthine oxidase, possibly decreasing production of oxygen-free radicals or promoting the accumulation of purines. Controlled studies are warranted to confirm these preliminary observations.

Topics: Aged; Aged, 80 and over; Aggression; Allopurinol; Dementia; Enzyme Inhibitors; Female; Free Radicals; Humans; Male; Treatment Outcome

Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported.. To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population.. Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout.. Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7-60.2) to 69.9 (95% confidence interval: 65.3-74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia.. This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia.

Topics: Allopurinol; Dementia; Female; Gout; Gout Suppressants; Humans; Hyperuricemia; Male; Prevalence

Topics: Aged; Allopurinol; Dementia; Humans; Medicare; Risk Factors; United States

Topics: Aged; Aged, 80 and over; Allopurinol; Dementia; Febuxostat; Female; Gout Suppressants; Humans; Male; Retrospective Studies; Risk Factors

The purpose of this study was to assess the comparative effectiveness of allopurinol versus febuxostat for preventing incident dementia in older adults.. In a retrospective cohort study using Medicare claims data, we included patients newly treated with allopurinol or febuxostat (baseline period of 365 days without either medication). We used 5:1 propensity-matched Cox regression analyses to compare the hazard ratio (HR) of incident dementia with allopurinol versus febuxostat use and with allopurinol/febuxostat dose and duration.. Crude rates of incident dementia per 100,000 person-days were lower with higher daily dose: allopurinol less than 200, 200 to 299, and at least 300 mg/day with 12, 9, and 8 and febuxostat 40 and 80 mg/day with 9 and 8, respectively. In propensity-matched analyses, compared with allopurinol use, febuxostat use was not significantly different, and the HR of incident dementia was 0.79 (95% confidence interval (CI) 0.61, 1.03). Compared with allopurinol less than 200 mg/day, higher allopurinol doses (200 to 299 and at least 300 mg/day) and the febuxostat 40 mg/day dose were each associated with lower HRs of dementia: 0.80 (95% CI 0.64, 0.98), 0.59 (95% CI 0.50, 0.71), and 0.64 (95% CI 0.47, 0.86), respectively. Compared with allopurinol use for 1 to 180 days, longer allopurinol or febuxostat use durations were not significantly associated with differences in HR of dementia (range of 0.76 to 1.14).. A dose-related reduction in the risk of dementia in older adults was noted with higher allopurinol dose and with febuxostat 40 mg daily dose. Future studies need to examine the mechanism of this benefit.

Topics: Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Dementia; Dose-Response Relationship, Drug; Febuxostat; Female; Gout Suppressants; Humans; Hyperuricemia; Incidence; Male; Propensity Score; Proportional Hazards Models; Retrospective Studies

Conflicting data in the literature raise the question whether gout, independent of its treatment, increases the risk of dementia in the elderly. Our objective was to assess whether gout in older adults is associated with the risk of incident dementia.. We used the 5% Medicare claims data for this observational cohort study. We used multivariable-adjusted Cox proportional hazard models to assess the association of gout with a new diagnosis of dementia (incident dementia), adjusting for potential confounders/covariates including demographics (age, race, sex), comorbidities (Charlson-Romano comorbidity index), and medications commonly used for cardiac diseases (statins, beta-blockers, diuretics, and angiotensin converting enzyme (ACE)-inhibitors) and gout (allopurinol and febuxostat).. In our cohort of 1.71 million Medicare beneficiaries, 111,656 had incident dementia. The crude incidence rates of dementia in people without and with gout were 10.9 and 17.9 per 1000 person-years, respectively. In multivariable-adjusted analyses, gout was independently associated with a significantly higher hazard ratio of incident dementia, with a HR of 1.15 (95% CI, 1.12, 1.18); sensitivity analyses confirmed the main findings. Compared to age 65 to < 75 years, age 75 to < 85 and ≥ 85 years were associated with 3.5 and 7.8-fold higher hazards of dementia; hazards were also higher for females, black race or people with higher medical comorbidity.. Gout was independently associated with a 15% higher risk of incident dementia in the elderly. Future studies need to understand the pathogenic pathways involved in this increased risk.

Topics: Adrenergic beta-Antagonists; Aged; Aged, 80 and over; Allopurinol; Cohort Studies; Comorbidity; Dementia; Female; Gout; Humans; Male; Medicare; Proportional Hazards Models; Retrospective Studies; Risk Factors; United States

The concomitant use of herb and prescription medications is increasing globally. Herb-drug interactions are therefore a clinically important problem. Yokukansan (YKS), a Japanese traditional herbal medicine, is one of the most frequently used herbal medicines. It is effective for treating the behavioral and psychological symptoms of dementia. We investigated the potential effects of YKS on drug-metabolizing enzyme activities in humans. An open-label repeat-dose study was conducted in 26 healthy Japanese male volunteers (age: 22.7±2.3 years) with no history of smoking. An 8-h urine sample was collected after a 150-mg dose of caffeine and a 30-mg dose of dextromethorphan before and after the administration of YKS (2.5 g, twice a day for 1 week). The activities of cytochrome P450 (CYP) 1A2, CYP2D6, CYP3A, xanthine oxidase (XO) and N-acetyltransferase 2 (NAT2) were assessed based on the urinary metabolic indices of caffeine and dextromethorphan, and the urinary excretion ratio of 6β-hydroxycortisol to cortisol. There were no statistically significant differences in the activities of the examined enzymes before or after the 7-d administration of YKS. Although further studies assessing the influence of YKS on the pharmacokinetics and pharmacodynamics of the substrates of the drug-metabolizing enzymes are needed to verify the present results, YKS is unlikely that a pharmacokinetic interaction will occur with concomitantly administered medications that are predominantly metabolized by the CYP1A2, CYP2D6, CYP3A, XO and NAT2.

Topics: Adult; Arylamine N-Acetyltransferase; Behavior; Caffeine; Cytochrome P-450 Enzyme System; Dementia; Dextromethorphan; Drug Interactions; Drugs, Chinese Herbal; Healthy Volunteers; Humans; Hydrocortisone; Male; Middle Aged; Xanthine Oxidase