Chronic Kidney Disease, Cognitive Decline, and Incident Dementia: the 3C Study

Objective: To evaluate the longitudinal relationship between moderate chronic kidney disease (CKD), decline in kidney function, and microalbuminuria with subsequent cognitive decline and incident dementia.

Methods: This study is based on a population-based cohort of 7,839 subjects over 65 years with 7 years of follow-up. Glomerular filtration rate was estimated (eGFR) using the CKD-EPI equation. Global cognitive function was assessed using the Mini-Mental State Examination (MMSE) and dementia was actively screened and diagnosed.

Results: At baseline, 12% of the participants had an eGFR <60 mL/min/1.73 m(2). A total of 564 incident dementia cases were diagnosed during the follow-up. Low baseline eGFR values were not associated with an increased risk of incident dementia or cognitive decline over the 7-year follow-up, except a borderline significant association with dementia with vascular component. However, eGFR decline over the first 4-year period was associated with higher risk of dementia with vascular component (relative risk = 5.35 [1.76-16.3] in those with eGFR decline >4 mL/min/1.73 m(2)/y compared with those <4) and with higher cognitive decline on the MMSE (-0.12 points, p < 0.01 in those with eGFR >4 mL/min/1.73 m(2)/y compared with those <4) in the 3 subsequent years. Proteinuria tended to be associated with an increased risk of subsequent dementia with vascular component.

Conclusions: Despite a large sample and a long follow-up, we found no increased risk of cognitive decline or dementia associated with low eGFR level. However, faster eGFR decline was associated with global cognitive decline and incident dementia with vascular component, suggesting that this association may be mediated by vascular mechanisms.