Faculty Bibliography

Models of memory consolidation posit a central role for reactivation of brain activity patterns during sleep, especially in non-Rapid Eye Movement (NREM) sleep. While such "replay" of recent waking experiences has been well-demonstrated in rodents, electrophysiological evidence of reactivation in human sleep is still largely lacking. In this intracranial study in patients with epilepsy (N = 9) we explored the spontaneous electroencephalographic reactivation during sleep of spatial patterns of brain activity evoked by motor learning. We first extracted the gamma-band (60-140 Hz) patterns underlying finger movements during a tapping task and underlying no-movement during a short rest period just prior to the task, and trained a binary classifier to discriminate between motor movements vs. rest. We then used the trained model on NREM sleep data immediately after the task and on NREM sleep during a control sleep period preceding the task. Compared with the control sleep period, we found, at the subject level, an increase in the detection rate of motor-related patterns during sleep following the task, but without association with performance changes. These data provide electrophysiological support for the reoccurrence in NREM sleep of the neural activity related to previous waking experience, i.e. that a basic tenet of the reactivation theory does occur in human sleep.

Background: The association between early changes in albuminuria and kidney and CV events is primarily based on trials of renin-angiotensin system blockade. It is unclear whether this association is similar with sodium-glucose cotransporter 2 inhibitors.
Method(s): In this post-hoc analysis of the CREDENCE trial in patients with type 2 diabetes and chronic kidney disease, we assessed the effect of CANA versus placebo on albuminuria at week 26, and the association of early changes in urinary albumin:creatinine ratio (UACR) for the first 26 weeks with kidney and CV outcomes using multivariable Cox regression. Kidney and CV outcomes were defined as (1) endstage kidney disease, doubling of serum creatinine or death due to kidney disease, (2) major adverse cardiovascular events (MACE) and (3) hospitalization for heart failure (HHF) or CV death.
Result(s): This analysis included 3836 participants (87.2%) with complete data for early changes in UACR. CANA lowered UACR by 31% (95%CI 27-36%) at week 26 and increased the likelihood of achieving a 30% UACR reduction (OR 2.69, 95%CI 2.35- 3.07). We observed log-linear associations of early changes in UACR during 26 weeks with kidney and CV outcomes (all p trend <0.001; Table). Each 30% UACR reduction was independently associated with a lower hazard for clinical outcomes, overall and in each treatment arm (all p <0.001).
Conclusion(s): In people with type 2 diabetes and CKD, canagliflozin results in early and sustained reductions in albuminuria, which was independently associated with longterm kidney and cardiovascular outcomes. (Table Presented)