High uric acid levels may protect against cognitive decline in ALS

Higher levels also linked to reduced risk of frontotemporal dementia in study

Andrea Lobo, PhD avatar

by Andrea Lobo, PhD |

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Having higher blood levels of uric acid may prevent or delay the decline in cognitive function in people with amyotrophic lateral sclerosis (ALS), according to a new study from Italy.

High levels of uric acid are also associated with reduced odds of frontotemporal dementia, a form of dementia especially common in ALS patients that’s marked by damage to the brain’s frontal and temporal regions, data show.

The study, “High serum uric acid levels are protective against cognitive impairment in amyotrophic lateral sclerosis,” was published in the Journal of Neurology.

Recent research has shown a significant proportion of people with ALS experience cognitive or behavioral changes. These most commonly affect a person’s ability to plan actions or regulate behaviors, but up to 20% of patients develop overt dementia, in which their thinking, memory, and social skills become so affected as to interfere with daily life.

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Uric acid produced from breakdown of natural substances called purines

Uric acid has emerged as a factor that can improve cognitive function, both in the general population and in people with neurodegenerative disorders. The molecule is produced from the breakdown of purines, natural substances found in the body, and can also be found in certain foods and beverages.

Data have suggested uric acid can protect nerve cells from damage, leading to better cognitive function in some patients with neurodegenerative disorders and in elderly people. However, it can also have detrimental effects in people with systemic conditions, in whom higher levels of the molecule are associated with worse cognition.

The correlation between uric acid levels and cognitive impairment has not been well-studied in people with ALS. To know more, researchers in Italy examined data from 841 patients at the Turin ALS Center from 2007 to 2018, who had undergone cognitive and behavioral testing and whose uric acid levels had been measured as part of their diagnostic workup.

Their mean age at cognitive examination was 66.8 years, and more than half (58.5%) were men.

After undergoing a battery of neuropsychological tests, 50.2% of patients were deemed as having normal cognition. The remaining had some form of cognitive impairment: 32.2% had intermediate cognitive impairment and 17.6% had frontotemporal dementia (FTD).

Results showed uric acid levels were significantly different among the three groups, being lower in FTD patients (271.8 micromol/L) compared with the other two groups (288.5 and 289.7 micromol/L). Similar results were obtained in a group of patients with C9orf72 mutations, the most common ALS-related mutations.

The proportion of patients with ALS-FTD was significantly higher in the 33% of people with the lower levels of uric acid, data showed.

Also, when people with no or intermediate cognitive impairment were compared with FTD patients, data showed that a 1 micromol/L decrease in uric acid levels increased the likelihood of having FTD by 20%-32%.

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Higher uric acid at diagnosis can be protective for mild cognitive impairment

In turn, uric acid levels were not associated with the presence of intermediate cognitive impairment. Only an older age at onset was linked to this type of cognitive impairment, which each year increase being correlated with a 3% higher likelihood of developing cognitive impairment.

“This finding could indicate that higher [uric acid] levels at diagnosis can be protective in patients with mild cognitive impairment, preventing their progression to full-blown [frontotemporal dementia],” the researchers wrote.

Blood levels of uric acid correlated with scores on tests assessing executive function, cognitive flexibility, verbal memory, non-verbal intelligence, and language.

“Together with the proposed role of [uric acid] as a prognostic factor in ALS, our data show that [it] can also be a protective factor for the cognitive-behavioral component of the disease,” the researchers wrote.

However, “further study on [uric acid] will better elucidate the mechanisms through which this metabolite may exert its protective activity in ALS,” they added.