CKD Associates with Cognitive Decline in Middle-Aged and Older Adults with Long-Standing Type 1 Diabetes

Abstract

Background: Individuals with chronic kidney disease (CKD) or type 1 diabetes (T1D) are at risk for cognitive decline, but it is unclear if these associations are with albuminuria, estimated glomerular filtration rate (eGFR), or both. Methods: We examined the longitudinal relationships between CKD and change in cognition in 1,051 participants with T1D in the Diabetes Control and Complications Trial (DCCT) and its follow-up, the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Albumin excretion rate (AER) and eGFR were measured every 1-2 years. Three cognitive domains were assessed repeatedly over a 32-year period: immediate memory; delayed memory; and psychomotor and mental efficiency. Associations between cognitive function and CKD were assessed 1) longitudinally, and 2) in models utilizing eGFR and albuminuria measurements over the first 15-20 years with subsequent change in cognitive function over the ensuing 14 years(when decline in cognition was greatest).. Results: In fully-adjusted longitudinal analyses, the magnitude of decline in the psychomotor and mental efficiency domain score was associated with eGFR <60 mL/min/1.73m2 (β -0.449, 95%CI [-0.640, -0.259]) and sustained AER 30-<300 mg/24hr (β -0.148, 95%CI [-0.270, -0.026]). This was equivalent to a decrease associated with approximately 11 and 4 years of ageing, respectively. In analyses focused on changes in cognition between study years 18 and 32, eGFR <60 mL/min/1.73m2 was associated with reduced psychomotor and mental efficiency (β -0.915, 95%CI [-1.613, -0.217]). Conclusions: In T1D, development of CKD was associated with a subsequent reduction on cognitive tasks requiring psychomotor and mental efficiency. These data highlight the need for increased recognition of risk factors for neurologic sequelae in patients with T1D, as well as preventive and treatment strategies to ameliorate cognitive decline.