Sex-Dependent Associations of Serum Uric Acid with Brain Function During Aging

Article type: Research Article

Authors: Kueider, Alexandra M.^a | An, Yang^b | Tanaka, Toshiko^c | Kitner-Triolo, Melissa H.^b | Studenski, Stephanie^c | Ferrucci, Luigi^c | Thambisetty, Madhav^{a; *}

Affiliations: [a] Unit of Clinical and Translational Neuroscience, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA | [b] Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA | [c] Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA

Correspondence: [*] Correspondence to: Madhav Thambisetty, MD, PhD, Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, 251 Bayview Blvd, Room 4B311, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA. Tel.: +1 410 558 8572; Fax: +1 410 558 8674; E-mail: thambisettym@mail.nih.gov.

Abstract: Serum uric acid (SUA) is an abundant natural antioxidant capable of reducing cellular oxidation, a major cause of neurodegenerative disease. In line with this, SUA levels are lower in Alzheimer’s disease; however, the association between SUA and cognition remains unclear. Results from studies examining the effects of SUA on cognition may be difficult to interpret in the context of normal versus pathological aging. This study examined sex-specific associations of baseline SUA with cognition during aging. Data from dementia-free participants initially aged 26–99 (N = 1,451) recruited for the Baltimore Longitudinal Study of Aging (BLSA), were used in the current analyses. SUA was assessed using blood samples collected during research visits. Cognition was measured using five composite scores (verbal memory, attention, executive function, language, and visuospatial ability). At the first study visit, compared with women, men were older, more likely to be White, had more years of education, higher baseline SUA levels, and higher cardiovascular risk scores. Higher baseline SUA was associated with attenuated declines in attention (β= 0.006; p = 0.03) and visuospatial abilities (β= 0.007; p = 0.01) in men. There was a trend to suggest higher baseline SUA in men was associated with attenuated declines in language, but this finding did not reach statistical significance (p = 0.09). There were no significant findings with SUA and cognition in women. In this sample of cognitively healthy, community-dwelling adults, we found that higher SUA levels at baseline were associated with attenuated declines in attention and visuospatial abilities in men. SUA was not associated with cognition or change in cognition over time in women.

Keywords: Aging, cognitive function, older adults, uric acid

DOI: 10.3233/JAD-170287

Journal: Journal of Alzheimer's Disease, vol. 60, no. 2, pp. 699-706, 2017