Subcortical amyloid load is associated with shape and volume in cognitively normal individuals.

Amyloid-beta (Aß) deposition is one of the main hallmarks of Alzheimer's disease. The study assessed the associations between cortical and subcortical 11 C-Pittsburgh Compound B (PiB) retention, namely, in the hippocampus, amygdala, putamen, caudate, pallidum, and thalamus, and subcortical morphology in cognitively normal individuals. We recruited 104 cognitive normal individuals who underwent extensive neuropsychological assessment, PiB-positron emission tomography (PET) scan, and 3-T magnetic resonance imaging (MRI) acquisition of T1-weighted images. Global, cortical, and subcortical regional PiB retention values were derived from each scan and subcortical morphology analyses were performed to investigate vertex-wise local surface and global volumes, including the hippocampal subfields volumes. We found that subcortical regional Aß was associated with the surface of the hippocampus, thalamus, and pallidum, with changes being due to volume and shape. Hippocampal Aß was marginally associated with volume of the whole hippocampus as well as with the CA1 subfield, subiculum, and molecular layer. Participants showing higher subcortical Aß also showed worse cognitive performance and smaller hippocampal volumes. In contrast, global and cortical PiB uptake did not associate with any subcortical metrics. This study shows that subcortical Aß is associated with subcortical surface morphology in cognitively normal individuals. This study highlights the importance of quantifying subcortical regional PiB retention values in these individuals.

Subcortical amyloid relates to cortical morphology in cognitively normal individuals.

PURPOSE: Amyloid (Aß) brain deposition can occur in cognitively normal individuals and is associated with cortical volume abnormalities. Aß-related volume changes are inconsistent across studies. Since volume is composed of surface area and thickness, the relative contribution of Aß deposition on each of these metrics remains to be understood in cognitively normal individuals. METHODS: A group of 104 cognitively normal individuals underwent neuropsychological assessment, PiB-PET scan, and MRI acquisition. Surface-based cortical analyses were performed to investigate the effects of cortical and subcortical Aß burden on cortical volume, thickness, and surface area. Mediation analyses were used to study the effect of thickness and surface area on Aß-associated volume changes. We also investigated the relationships between structural metrics in clusters with abnormal morphology and regions underlying resting-state functional networks and cognitive performance. RESULTS: Cortical Aß was not associated with cortical morphology. Subcortical Aß burden was associated with changes in cortical volume, thickness, and surface area. Aß-associated volume changes were driven by cortical surface area with or without thickness but never by thickness alone. Aß-associated changes overlapped greatly with regions from the default mode network and were associated with lower performance in visuospatial abilities, episodic memory, and working memory. CONCLUSIONS: In cognitively normal individuals, subcortical Aß is associated with cortical volume, and this effect was driven by surface area with or without thickness. Aß-associated cortical changes were found in the default mode network and affected cognitive performance. Our findings demonstrate the importance of studying subcortical Aß and cortical surface area in normal ageing.

NREM2 and Sleep Spindles Are Instrumental to the Consolidation of Motor Sequence Memories.

Although numerous studies have convincingly demonstrated that sleep plays a critical role in motor sequence learning (MSL) consolidation, the specific contribution of the different sleep stages in this type of memory consolidation is still contentious. To probe the role of stage 2 non-REM sleep (NREM2) in this process, we used a conditioning protocol in three different groups of participants who either received an odor during initial training on a motor sequence learning task and were re-exposed to this odor during different sleep stages of the post-training night (i.e., NREM2 sleep [Cond-NREM2], REM sleep [Cond-REM], or were not conditioned during learning but exposed to the odor during NREM2 [NoCond]). Results show that the Cond-NREM2 group had significantly higher gains in performance at retest than both the Cond-REM and NoCond groups. Also, only the Cond-NREM2 group yielded significant changes in sleep spindle characteristics during cueing. Finally, we found that a change in frequency of sleep spindles during cued-memory reactivation mediated the relationship between the experimental groups and gains in performance the next day. These findings strongly suggest that cued-memory reactivation during NREM2 sleep triggers an increase in sleep spindle activity that is then related to the consolidation of motor sequence memories.