Association Between Renal Function and Cognitive Performance in Elderly Community‐dwelling Men Without Dementia

To the Editor: We read with great interest the recent article by Yaffe and colleagues1 that stated that poorer cognitive function was associated with poorer kidney function in a large sample of older adults with chronic kidney disease (CKD). In light of that and other reports,2-6 CKD has been linked to the risk of cognitive decline in middle-aged and older adults, although the presence of cognitive impairment (or clinical dementia) could result in decline in ability to perform activities of daily living and thus poor physical condition (e.g., dehydration). It remains unclear whether kidney function may affect cognitive performance in older people without dementia. Therefore, we would like to add our data to the association of medical confounders with cognitive performance based on an older community-dwelling sample without dementia. We also tested whether renal function was associated with specific domains of aging cognition. We analyzed 228 subjects (100% male; aged 79.4±4.9, range 63–98; 5.8±4.7 years of education, range 0–16) derived from our previously published works regarding the analysis of the genetic association of cognitive function7 and cardiovascular physiology8 in older Chinese men without dementia and with normal function of daily activities. These subjects had full physical and laboratory profiles available, including body mass index, heart rate, blood pressure, hemoglobin, fasting blood sugar, lipid, liver, and kidney function tests. Cognitive functions were assessed using the Cognitive Abilities Screening Instrument (CASI; mean±SD 84.7±9.1, range 54–100).9 The CASI is a 100-point cognitive test that provides quantitative assessment in nine domains of cognitive function (long-term memory, short-term memory, attention, concentration and mental manipulation, orientation, abstraction and judgment, language, visual construction, and list-generating fluency). Multiple linear regression analysis with a forward stepwise method was used to identify significant predictors of cognitive performance, using the CASI assessment as a dependent variable and age, education duration, and physical and laboratory data as predictors. A general linear model was used to assess the difference in cognitive performance between subgroups with and without CKD, controlling for predictors identified in the regression model. According to the estimated glomerular filtration rate (eGFR) data, 117 (51.3%) subjects had normal kidney function (eGFR>60 mL/min per 1.73 m2), 104 (45.6%) had Stage 3 CKD, six (2.6%) had Stage CKD 4, and one (0.4%) had Stage 5 CKD. Table 1 summarizes the significant predictors accounting for the total CASI score and its component scores. Total CASI score correlated positively with education (correlation coefficient (r)=0.24, P<.001) and eGFR (r=0.18, P=.008). For CASI components, kidney function was associated with concentration and mental manipulation (blood urea nitrogen (BUN) r=−0.19, P=.007), orientation (BUN: r=−0.20, P=.004), drawing (eGFR: r=0.22, P=.001), and list generating fluency (eGFR: r=0.16, P=.02). In addition, systolic blood pressure was correlated negatively with attention (r=−0.21, P=.002) and abstract thinking (r=−0.18, P=.008). Triglyceride level was correlated negatively with short-term memory (r=−0.15, P=.03). In a comparison of subgroups with and without CKD, CASI was significantly lower in subjects with CKD than in those with normal kidney function (82.9±9.4 vs 86.4±8.6, F=7.02, P=.009). For CASI components, subgroups according to CKD differed significantly only in drawing category (CKD vs control: 7.6±2.5 vs 8.7±1.8, F=8.93, P=.003). In accordance with previously published reports, these findings indicate a weak but significant association between renal function and cognitive performance in elderly community-dwelling men without dementia. The eGFR predicted 3.2% variance of CASI data and was linked to executive functions such as drawing and list-generating fluency. The findings complement prior reports in that the study sample was screened and excluded for presence of clinical dementia, reducing the confounding effect of cognitive impairment on physical conditions. BUN, a marker for nitrogenous waste, was associated with concentration and orientation. Significantly higher BUN could result in neurological disturbances, such as delirium or uremic encephalopathy. These results suggest that in older adults without dementia, variations in BUN level (average 19.9±8.3 in the current study) could alter orientation or concentration and add to the mechanisms of association between CKD and cognitive impairment. Study limitations include that this was a cross-sectional study and that all of the participants were male. Other physiological confounders might be present. For example, it has been shown preliminarily that autonomic function is associated with cognitive performance.10 Despite these limitations, the current study showed that CKD is associated with lower but normal cognitive performance in an older population without dementia. CKD may be a cause or a consequence of dementing symptoms. A longitudinal study is warranted to examine the risk of dementia associated with CKD. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. This study was supported by Taipei Veterans General Hospital (V95ER3-003, V96ER3-002, V97ER3-003, and V97C1-132).