Albuminuria and Microalbuminuria as Predictors of Cognitive Performance in a General Population: An 11-Year Follow-Up Study

Article type: Research Article

Authors: Ekblad, Laura L.^{a; *} | Toppala, Sini^{a; b} | Johansson, Jouni K.^{c; d} | Koskinen, Seppo^e | Sundvall, Jouko^e | Rinne, Juha O.^{a; f} | Puukka, Pauli^c | Viitanen, Matti^{b; g} | Jula, Antti^c

Affiliations: [a] Turku PET Centre, University of Turku, c/o Turku University Hospital, Turku, Finland | [b] Turku City Hospital, University of Turku, Turku, Finland | [c] National Institute for Health and Welfare, Turku, Finland | [d] Welfare Division of Turku City, Turku, Finland | [e] National Institute for Health and Welfare, Helsinki, Finland | [f] Division of Clinical Neurosciences, Turku University Hospital, Turku, Finland | [g] Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden

Correspondence: [*] Correspondence to: Laura L. Ekblad, MD, Turku PET Centre, c/o Turku University Hospital, PO Box 52, 20521 Turku, Finland. Tel.: +358 23131879; Fax: +358 22318191; E-mail: llekbl@utu.fi.

Abstract: Microalbuminuria, defined as urine albumin-to-creatinine ratio (UACR)>3.0 mg/mmol and ≤ 30 mg/mmol, is an early marker of endothelial damage of the renal glomeruli. Recent research suggests an association among microalbuminuria, albuminuria (UACR > 3.0 mg/mmol), and cognitive impairment. Previous studies on microalbuminuria, albuminuria, and cognition in the middle-aged have not provided repeated cognitive testing at different time-points. We hypothesized that albuminuria (micro- plus macroalbuminuria) and microalbuminuria would predict cognitive decline independently of previously reported risk factors for cognitive decline, including cardiovascular risk factors. In addition, we hypothesized that UACR levels even below the cut-off for microalbuminuria might be associated with cognitive functioning. These hypotheses were tested in the Finnish nationwide, population-based Health 2000 Survey (n = 5,921, mean age 52.6, 55.0% women), and its follow-up, Health 2011 (n = 3,687, mean age at baseline 49.3, 55.6% women). Linear regression analysis was used to determine the associations between measures of albuminuria and cognitive performance. Cognitive functions were assessed with verbal fluency, word-list learning, word-list delayed recall (at baseline and at follow-up), and with simple and visual choice reaction time tests (at baseline only). Here, we show that micro- plus macroalbuminuria associated with poorer word-list learning and a slower reaction time at baseline, with poorer word-list learning at follow-up, and with a steeper decline in word-list learning during 11 years after multivariate adjustments. Also, higher continuous UACR consistently associated with poorer verbal fluency at levels below microalbuminuria. These results suggest that UACR might have value in evaluating the risk for cognitive decline.

Keywords: Albuminuria, cognition, cognitive decline, longitudinal study, microalbuminuria

DOI: 10.3233/JAD-170972

Journal: Journal of Alzheimer's Disease, vol. 62, no. 2, pp. 635-648, 2018