Hyperuricemia is a condition of excess uric acid levels in the blood. This condition is the cause of gout arthritis. Meanwhile, dementia is a condition in which the brain's ability is decreased in performing basic functions such as thinking, remembering, speaking, and making decisions). People with dementia usually difficult to take care of themselves, have difficulty communicating with those around them, and have difficulty understanding what they see.

Can Hyperuricemia cause Dementia?
Ilustration Dementia Patient
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Can hyperuricemia increase the risk of dementia?

Uric acid is a natural antioxidant useful for inhibiting oxidative stress and preventing damage to body cells. The decrease in uric acid levels is considered to increase the risk of neurodegenerative diseases. It is based on uric acid's role as an antioxidant. Many studies have also shown that gout is also closely linked to the incidence of obesity, cardiovascular diseases, and medical conditions associated with oxidative stress.

Dementia and cognitive impairment are also known to be associated with vascular pathology and oxidative stress, so that uric acid as an antioxidant is thought to play a role in preventing this. But recent studies have shown that there is an association between hyperuricemia and increased dementia risk.
Studies regarding the association between serum uric acid levels and dementia are inconclusive because most studies use cross-sectional methods and have a high risk of bias. Therefore, the results are still debated.

Research states that uric acid's paradoxical nature is based on its ability as an oxidant (intra-cell) and antioxidant (in plasma), so that uric acid is considered to play a role in the pathogenesis of these diseases.


Scientific Evidence Regarding the Association between Hyperuricemia and the Risk of Dementia

The European League Against Rheumatism and the American College of Rheumatology recommend keeping serum uric acid levels below 360 μmol / L and below 300 μmol / L for certain cases. High uric acid levels (> 6 mg / dL for men and> 5 mg / dL for women) are thought to cause brain vascular changes that lead to dementia. Long before dementia symptoms appeared, changes in the brain began slowly and without symptoms (a chronic pathological process). Therefore, uric acid's effect on brain vascular can only be seen from MRI, such as hippocampal atrophy or white matter atrophy characterized by "white matter hyperintensities" (WMH) on MRI, which has been recognized as a strong predictor of cognitive impairment.

In contrast, in 2009, a study in Rotterdam reported that hyperuricemia decreased the risk of dementia and improved cognitive abilities. However, it should be noted that this study was analyzed by adjusting for cardiovascular risk (vascular pathological processes), while the process of developing dementia due to hyperuricemia is closely related to vascular processes.

A 2010 study by Latourte et al. studied 1924 MRI brain scans of patients at a 12-year follow-up and found an opposite result. The result is that hyperuricemia increases the risk of dementia in people aged ≥ 65 years. Hyperuricemia is considered to increase vascular or mixed dementia risk, but not Alzheimer's dementia (neurodegenerative, not vascular). This is due to pathological processes resulting from hyperuricemia associated with intravascular processes. This explains the absence of an association between hyperuricemia and increased dementia risk in the 2009 Rotterdam study.

The next cross-sectional publication in 2013 by Verhaaren et al., which is a continuation of the Rotterdam study, also supports the association between hyperuricemia and poorer cognitive levels and the presence of WMH on MRI examination.

Thus, several recent studies have shown that a slight elevate in serum uric acid levels can lead to brain function changes and cognitive decline, especially in the elderly. It should be noted that subjects with gout (considered a population with high uric acid levels) were found to have more cardiovascular comorbidities - suggesting a vascular pathological condition.

Meanwhile, the association between hyperuricemia and WMH became less significant when subjects with gout were excluded. This confirms that hyperuricemia causes vascular disorders (including brain vascularization) to cause the brain's alba substance atrophy and leads to dementia.



Conclusion
Hyperuricemia can increase the risk of developing vascular or mixed-type dementia, but not Alzheimer's dementia. This is because hyperuricemia induces intravascular pathological processes, including in the brain, causing atrophy of the alba substance (characterized by finding WMH on MRI) and causing dementia.

On the other hand, hyperuricemia is also associated with an increased risk of cardiovascular disease (a risk factor for vascular dementia). Therefore, further research is still needed to determine the causal relationship between hyperuricemia and dementia. However, doctors should aim to reduce uric acid levels to normal levels in patients at risk of developing vascular dementia.