Reduced overnight memory consolidation and associated alterations in sleep spindles and slow oscillations in early Alzheimer's disease.

Spatial navigation critically underlies hippocampal-entorhinal circuit function that is early affected in Alzheimer's disease (AD). There is growing evidence that AD pathophysiology dynamically interacts with the sleep/wake cycle impairing hippocampal memory. To elucidate sleep-dependent consolidation in a cohort of symptomatic AD patients (n = 12, 71.25 ± 2.16 years), we tested hippocampal place learning by means of a virtual reality task and verbal memory by a word-pair association task before and after a night of sleep. Our results show an impaired overnight memory retention in AD compared with controls in the verbal task, together with a significant reduction of sleep spindle activity (i.e., lower amplitude of fast sleep spindles, p = 0.016) and increased duration of the slow oscillation (SO; p = 0.019). Higher spindle density, faster down-to-upstate transitions within SOs, and the time delay between SOs and nested spindles predicted better memory performance in healthy controls but not in AD patients. Our results show that mnemonic processing and memory consolidation in AD is slightly impaired as reflected by dysfunctional oscillatory dynamics and spindle-SO coupling during NonREM sleep. In this translational study based on experimental paradigms in animals and extending previous work in healthy aging and preclinical disease stages, our results in symptomatic AD further deepen the understanding of the memory decline within a bidirectional relationship of sleep and AD pathology.

Deep brain stimulation of the subthalamic nucleus restores spatial reversal learning in patients with Parkinson's disease.

Spatial learning and navigation are supported by distinct memory systems in the human brain such as the hippocampus-based navigational system and the striatum-cortex-based system involved in motor sequence, habit and reversal learning. Here, we studied the role of subthalamic circuits in hippocampus-associated spatial memory and striatal-associated spatial reversal learning formation in patients with Parkinson's disease, who underwent a deep brain stimulation of the subthalamic nucleus. Deep brain stimulation patients (Parkinson's disease-subthalamic nucleus: n = 26) and healthy subjects (n = 15) were tested in a novel experimental spatial memory task based on the Morris water maze that assesses both hippocampal place memory as well as spatial reversal learning. All subjects were trained to navigate to a distinct spatial location hidden within the virtual environment during 16 learning trials in a subthalamic nucleus Stim-On condition. Patients were then randomized into two groups with either a deep brain stimulation On or Off condition. Four hours later, subjects were retested in a delayed recall and reversal learning condition. The reversal learning was realized with a new hidden location that should be memorized during six consecutive trials. The performance was measured by means of an index indicating the improvement during the reversal learning. In the delayed recall condition, neither patients, healthy subjects nor the deep brain stimulation On- versus Off groups showed a difference in place memory performance of the former trained location. In the reversal learning condition, healthy subjects (reversal index 2.0) and patients in the deep brain stimulation On condition (reversal index 1.6) showed a significant improvement. However, patients in the deep brain stimulation Off condition (reversal index 1.1) performed significantly worse and did not improve. There were no differences between all groups in a final visual guided navigation task with a visible target. These results suggest that deep brain stimulation of subthalamic nucleus restores spatial reversal learning in a virtual navigation task in patients with Parkinson's disease and gives insight into the neuromodulation effects on cognition of subthalamic circuits in Parkinson's disease.