IC‐P‐131: HUMAN IN VIVO TAU PATHOLOGY, IMPAIRED NREM SLEEP OSCILLATIONS AND MEMORY DECLINE IN AGING

Aging disrupts sleep. Moreover, these sleep impairments are exaggerated in Alzheimer's disease, and are proposed to contribute to cognitive decline. Recent human studies have linked β-amyloid with non-rapid eye-movement (NREM) sleep disruption. However, the impact of tau pathology on human sleep oscillations and cognition remains uninvestigated. Here, we tested the hypothesis that tau burden within medial temporal lobe (MTL) impairs the coupled relationship between the two key NREM sleep oscillations—sleep spindles and slow waves, and their known support of hippocampal memory. In vivo tau was measured with [18F]AV1451 PET in cognitively normal older adults (n=19, mean age=75.8), together with overnight, dense-array sleep EEG recordings. A validated associative recognition task was used to measure hippocampal memory function. Analyses focused on relationships between three measurements: (i) AV1451 tau PET binding in MTL measured as the mean (L+R) standardized uptake value ratio of tracer relative to inferior cerebellar gray matter (SUVR), (ii) EEG phase-amplitude coupling between NREM spindles and slow wave oscillations, and (iii) hippocampus-dependent memory. Worse memory performance was related to greater tau burden in MTL (AV1451 SUVR; p=0.03; Fig. 1). MTL tau burden additionally predicted the severity of impaired sleep spindle-slow wave oscillation coupling over the prefrontal cortex (p=0.03; Fig. 2, top). Moreover, this tau-related sleep disruption of spindle-slow wave coupling predicted the degree of memory impairment (p=0.05; Fig. 2, bottom).