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People with gout appeared less likely to develop dementia than age- and sex-matched peers, a database study from Korea found.

The analysis of more than 5,000 gout patients and 25,000 controls in Korea's national healthcare system yielded adjusted hazard ratios of 0.79 for overall new-onset dementia (95% CI 0.62-1.00) and 0.73 for Alzheimer's disease (95% CI 0.54-0.98), reported Ji Hyoun Kim, MD, and colleagues at Chungbuk National University Hospital in Cheongju, South Korea.

Men 65 and older drove the associations, with hazard ratios of 0.71 for overall dementia among gout patients in this age group (95% CI 0.52-0.97), and 0.67 for Alzheimer's disease (95% CI 0.46-0.97), the researchers reported in .

In contrast, gout diagnosis had no association with any type of incident dementia for those younger than 65, although Kim and colleagues found nonsignificant trends toward greater risk of vascular dementia among non-elderly male gout patients and greater likelihood of Alzheimer's disease for younger women with gout.

Furthermore, although women 65 and older with gout showed hazard ratios of 0.65-0.88 for overall, vascular, and Alzheimer's dementia, none of these were statistically significant.

"These results suggest that the association between gout and dementia type may differ based on the age of onset of gout and disease duration and different mechanisms may be involved," Kim and colleagues concluded.

Gout is both a metabolic and inflammatory disease, the authors observed, which could account for the mixed findings. On one hand, uric acid (elevated in active gout) is an antioxidant, and thus hypothetically could be neuroprotective in the brain. On the other, the inflammation that causes gout's clinical symptoms may contribute to neuropathology.

Not surprisingly, previous studies of cognition in people with rheumatologic disease have yielded mixed results: some showing no association, while others (particularly in rheumatoid arthritis, which doesn't involve antioxidant molecules) have found heightened risk for cognitive impairment. Across many of these studies, gout seemed to promote vascular dementia especially.

For the current study, Kim and colleagues looked for gout patients in a pre-existing representative sample of 1 million people enrolled in South Korea's national health insurance system. For each gout patient, the researchers then identified five non-gout controls of the same age, sex, and year of inclusion. Anyone with an existing dementia diagnosis was excluded.

Only vascular and Alzheimer's dementia were examined in the study; the investigators also included a category of "mixed" for those with both, and these were summed for analysis of overall dementia. (Frontotemporal and other less common forms of dementia were not considered.) Mean follow-up for subsequent development of dementia was just under 5 years.

Baseline demographics were as follows:

• Men were 92.4% the sample
• Mean age was 57; 17% younger than 40, 59% 40 to 64, 24% 65 and older
• About 15% were low-income

The gout and control groups differed substantially in their attendant comorbidities. Hypertension was especially prevalent in the gout group (61% vs 37% among controls), and diabetes, dyslipidemia, history of cerebrovascular events, and depression were also significantly more common with gout.

Mean incidence rates per 1,000 person-years for the three dementia categories were:

• Alzheimer's: 2.35 gout, 3.26 control
• Vascular: 0.81 gout, 0.78 control
• Mixed: 0.50 gout, 0.58 control

The wide confidence intervals for the study's hazard ratios resulted from the relatively small number of new-onset dementias seen in the study -- in the gout group, only 18 developed vascular dementia and 11 were diagnosed with both vascular and Alzheimer's dementia.

Other study limitations included a lack of data on important co-factors, such as smoking and drinking habits and family history. The dataset also didn't include gout patients' uric acid levels, which might have shed light on the neuroprotection hypothesis. Kim and colleagues also noted that the follow-up duration varied among participants.

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