# Response to: 'Uric acid and incident dementia: a population-based cohort study' by Lee and Song

Augustin Latourte, Aicha Soumaré, Thomas Bardin, Stéphanie Debette, Pascal Richette

<figure><img src="image_1.png" /></figure>

## To cite this version:

Augustin Latourte, Aicha Soumaré, Thomas Bardin, Stéphanie Debette, Pascal Richette. Response to: 'Uric acid and incident dementia: a population-based cohort study' by Lee and Song. Annals of the Rheumatic Diseases, 2018, 77 (9), pp.e63. 10.1136/annrheumdis-2017-212582. hal-03194293

HAL Id: hal-03194293

https://hal.science/hal-03194293v1

Submitted on 31 Mar 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
## Response to: 'Uric acid and incident dementia: a population-based cohort study' by Lee and Song

We thank Drs Lee and Song for their interest and comments concerning our recent population-based cohort study investigating the relationship between serum uric acid (SUA) levels and dementia in elderly patients.¹² They shared their concerns about the association that we found between higher SUA levels at baseline and an increased risk of incident vascular or mixed dementia. As discussed in our paper, these findings contradict a previous prospective study conducted in the Rotterdam cohort, which suggested that higher SUA levels were associated with a decreased risk of dementia and better cognitive function later in life.<fnref n="3" />

Drs Lee and Song highlighted that the association between higher SUA levels and dementia might be mediated by cardiovascular risk factors. This is indeed one of the key message of our study, in which we found a stronger association with vascular or mixed dementia, a subtype of dementia with a vascular component, than with Alzheimer's disease.<fnref n="1" /> Whereas the association was maintained after adjustment for traditional cardiovascular risk factors, it was no longer significant after adjustment for interim strokes, suggesting a mediating effect of cerebrovascular disease. We also found a non-significant trend for an association between higher SUA levels and brain MRI markers of cerebrovascular burden, consistently with previous data.<fnref n="4" />⁻<fnref n="6" /> Also, a previous study reported that the association between higher SUA levels and cognitive impairment was mediated by cerebral ischaemia.⁷ The relationship between uric acid (UA) and vascular dementia is also indirectly supported by the association between hyperuricaemia and several cardiovascular risk factors, such as hypertension.⁸ We agree that some dietary factors which were not evaluated in our study might be of importance, and this remains a topic for future research.

Development of dementia results from a long and silent preclinical process. In this perspective, we have also discussed the lack of multiple measurements of SUA levels over time as a limitation of our study. The sample of participants taking urate-lowering therapy (ULT) was also too small to evaluate its impact in our study. These are common issues in the field, which also apply to the Rotterdam study.<fnref n="3" /> A recent study by Singh *et al* found no significant association between initiation of ULT and the risk of subsequent dementia, but the specific impact of SUA levels was not investigated.⁹ We concur with Drs Lee and Song that future research should consider change in SUA levels over time, especially under ULT, to better understand the impact of UA on dementia.

Finally, we would like to emphasise that the antioxidant properties of UA are still debated.¹⁰⁻¹¹ A recent preclinical study found that UA might have neurotoxic effects.¹² Two recent meta-analyses of mostly cross-sectional studies did not establish a clear relationship between UA and neurodegenerative dementia.¹³⁻¹⁴ Thus, we agree with Drs Lee and Song that no causal relationship between UA and Alzheimer's disease can be formally established to date, but our study supports an association with vascular or mixed dementia. There is undoubtedly a strong need for further research to better understand the role of SUA in the pathogenesis of each subtype of dementia. Until then, we believe that

prescribers should continue to treat hyperuricaemia whenever it is appropriate.

Augustin Latourte,<fnref n="1" />,<fnref n="2" /> Aicha Soumaré,<fnref n="3" /> Thomas Bardin,<fnref n="1" />,<fnref n="2" />
Stéphanie Debette,<fnref n="3" />,<fnref n="4" />,<fnref n="5" />,<fnref n="6" /> Pascal Richette<fnref n="1" />,<fnref n="2" />

**Correspondence to** Professor Pascal Richette, Rheumatology Department, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Inserm U1132, UFR de Médecine, Université Paris Diderot, Paris 75013, France; pascal.richette@aphp.fr

**Competing interests** None declared.

**Provenance and peer review** Commissioned; internally peer reviewed.

► http://dx.doi.org/10.1136/annrheumdis-2017-212570

Ann Rheum Dis 2018;77:e63. doi:10.1136/annrheumdis-2017-212582

## REFERENCES

1. Lee YH, Song GG. Uric acid and incident dementia: a population-based cohort study. *Ann Rheum Dis* 2017;annrheumdis-2017-212570.

2. Latourte A, Soumaré A, Bardin T, et al. Uric acid and incident dementia over 12 years of follow-up: a population-based cohort study. *Ann Rheum Dis* 2018;77:328–35.

3. Euser SM, Hofman A, Westendorp RG, et al. Serum uric acid and cognitive function and dementia. *Brain* 2009;132:377–82.

4. Fanning JP, Wong AA, Fraser JF. The epidemiology of silent brain infarction: a systematic review of population-based cohorts. *BMC Med* 2014;12:119.

5. Shih CY, Chen CY, Wen CJ, et al. Relationship between serum uric acid and cerebral white matter lesions in the elderly. *Nutr Metab Cardiovasc Dis* 2012;22:154–9.

6. Schretlen DJ, Inscore AB, Vannorsdall TD, et al. Serum uric acid and brain ischemia in normal elderly adults. *Neurology* 2007;69:1418–23.

7. Vannorsdall TD, Jinnah HA, Gordon B, et al. Cerebral ischemia mediates the effect of serum uric acid on cognitive function. *Stroke* 2008;39:3418–20.

8. Wang J, Qin T, Chen J, et al. Hyperuricemia and risk of incident hypertension: a systematic review and meta-analysis of observational studies. *PLoS One* 2014;9:e114259.

9. Singh JA, Cleveland JD. Use of urate-lowering therapies is not associated with an increase in the risk of incident dementia in older adults. *Ann Rheum Dis* 2018;77:1243–5.

10. So A, Thorens B. Uric acid transport and disease. *J Clin Invest* 2010;120:1791–9.

11. Hershfield MS, Roberts LJ 2nd, Ganson NJ, et al. Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo. *Proc Natl Acad Sci U S A* 2010;107:14351–6.

12. Desideri G, Gentile R, Antonosante A, et al. Uric acid amplifies Aβ amyloid effects involved in the cognitive dysfunction/dementia: evidences from an experimental model in vitro. *J Cell Physiol* 2017;232:1069–78.

13. Khan AA, Quinn TJ, Hewitt J, et al. Serum uric acid level and association with cognitive impairment and dementia: systematic review and meta-analysis. *Age* 2016;38:16.

14. Chen X, Guo X, Huang R, et al. Serum uric acid levels in patients with Alzheimer's disease: a meta-analysis. *PLoS One* 2014;9:e94084.

<footnote n="1">¹Rheumatology Department, Hôpital Lariboisière, Assistance Publique-Hôpitaux de Paris, Paris, France</footnote>

<footnote n="2">²Inserm U1219, UFR de Médecine, Université Paris Diderot, Paris, France</footnote>

<footnote n="3">³Inserm Centre Bordeaux Population Health (U1219), Bordeaux, France</footnote>

<footnote n="4">⁴University of Bordeaux, Bordeaux, France</footnote>

<footnote n="5">⁵Department of Neurology, Memory Clinic, Bordeaux, France</footnote>

<footnote n="6">⁶Department of Neurology, Framingham Heart Study, Boston University School of Medicine, Boston, USA</footnote>