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

KEY POINTS: We found that development of both albuminuria and reduced eGFR was associated with clinically significant cognitive decline, particularly in the psychomotor and mental efficiency domain. There was also a significant interaction between worsened albuminuria and eGFR, the combination of which augmented cognitive deficits. A more comprehensive longitudinal phenotype of albuminuria showed that regressed albuminuria did not associate with worsened cognitive decline, as opposed to persistent albuminuria. BACKGROUND: Individuals with CKD or type 1 diabetes (T1D) are at risk for cognitive decline, but it is unclear whether these associations are with albuminuria, eGFR, or both. METHODS: We examined the longitudinal relationships between CKD and change in cognition in 1051 participants with T1D in the Diabetes Control and Complications Trial and its follow-up, the Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate 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 using 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 per 1.73 m(2) (β −0.449; 95% confidence interval [CI], −0.640 to −0.259) and sustained albumin excretion rate 30 to <300 mg/24 hours (β −0.148; 95% CI, −0.270 to −0.026). This was equivalent to a decrease associated with approximately 11 and 4 years of aging, respectively. In analyses focused on changes in cognition between study years 18 and 32, eGFR <60 ml/min per 1.73 m(2) was associated with reduced psychomotor and mental efficiency (β −0.915; 95% CI, −1.613 to −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.