The Relation of Uric Acid to Brain Atrophy and Cognition: The Rotterdam Scan Study

Abstract

Background: Uric acid has been associated with focal vascular brain disease. However, it is unknown whether uric acid also relates to global brain changes such as brain atrophy. We therefore studied the relation of uric acid to brain atrophy and whether this is accompanied by worse cognitive function. Methods: In 814 persons of the population-based Rotterdam Study (mean age 62.0 years), we studied the relation of uric acid levels to brain tissue atrophy and cognition using linear regression models adjusted for age, sex and putative confounders. Brain atrophy was assessed using automated processing of magnetic resonance imaging. Cognition was assessed using a validated neuropsychological test battery and we computed compound scores of cognitive domains. Results: Higher uric acid levels were associated with white matter atrophy [difference in Z-score of white matter volume per standard deviation increase in uric acid: -0.07 (95% CI: -0.12; -0.01)], but not with gray matter atrophy. This was particularly marked when comparing hyperuricemic to normouricemic persons [Z-score difference: -0.27 (-0.43; -0.11)]. Worse cognition was primarily found in persons with hyperuricemia [-0.28 (-0.48; -0.08)]. Conclusions: Hyperuricemia is related to white matter atrophy and worse cognition.

Higher baseline serum uric acid is associated with poorer cognition but not rates of cognitive decline in women

“…These findings are consistent with previous reports that higher levels of serum uric acid are associated cross-sectionally with poorer attention and working memory, psychomotor speed, and executive functioning (Schretlen and others 2007, Verhaaren and others 2013). They also are consistent with evidence that higher levels of serum uric acid correlate with greater white matter atrophy (Verhaaren and others 2013) and cerebral ischemic burdened as measured by the volume of hyperintense signal on T2-weighted brain MRI scans of older adults (Schretlen and others 2007), which likely mediates the relationship between increased serum uric acid and cognitive dysfunction (Vannorsdall and others 2008). …”

“…At baseline, one-quarter of the study participants had elevated serum uric acid. Given that serum uric acid levels were relatively stable over time, it is possible that baseline elevations in uric acid occurred in midlife or earlier in late life, causing brain changes (Vannorsdall and others 2008; Verhaaren and others 2013) that produced subtle cognitive decline prior to study enrollment. In order to clarify this, it would be helpful to assay serum uric acid in relation to cognition longitudinally in a sample of younger adults as they transition from normal to hyperuricimic status.…”

“…Recently, higher uric acid was associated with poorer processing speed and executive functioning as well as greater white matter atrophy in Rotterdam Scan study participants (Verhaaren and others 2013). We previously found a similarly deleterious association between mildly elevated serum uric acid and brain structure and function.…”

Serum Metabolomic Biomarkers of Dementia

“…Uric acid has previously been examined in relation to memory and dementia with mixed findings [31,32]. Consistent with the present observations, high circulating uric acid levels were associated with dementia in a population-based study [33], with low cognitive performance [34], and with increased risk of cognitive decline among older adults [35]. Thus, our observations of upregulation of metabolites for demented patients and incident cases confirm and extend previous findings.…”

Updated Eular Guidelines for the Management of Gout. Comments on Certain Items

“…Так, недавний метаанализ, включивший 11 исследований, неожиданнейшим образом засвидетельствовал отсутствие различий в сывороточном уровне МК при болезни Альц-геймера в сравнении со здоровым контролем [98]. Один из фрагментов крупного исследования Rotterdam Scan Study нашел прямую корреляцию между сывороточным уровнем МК и атрофией белого вещества, а также худшими показа-телями по шкалам, оценивающим когнитивные функции у лиц с гиперурикемией [99].…”