REGIONAL DEFICIT IN SLEEPING BRAIN ACTIVITY ASSOCIATED WITH TAU AND AMYLOID PATHOLOGY IN COGNITIVELY HEALTHY MIDDLE-AGED ADULTS

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Slow wave sleep is critical for memory function and brain regions that support slow wave activity are among those affected earliest in the AD process. Recent work suggests that sleep and AD pathology may have a reciprocal relationship for reasons not fully understood. The goal of this study was to assess the relationship between local deficits in slow wave sleep and accumulation of AD neuropathology among cognitively asymptomatic middle-aged adults. We hypothesized that local deficits in slow wave power would be associated with greater AD neuropathology. 20 participants (mean age 57+/- 4 years, 95% female, 70% with parental history of AD) were recruited from the Wisconsin Alzheimer's Disease Research Center. Only those who were cognitively asymptomatic and did not have sleep apnea were included. AD neuropathology was assessed using cerebrospinal fluid (CSF) that was collected via lumbar puncture and assayed for Aβ42 and T-Tau. Neuropathological burden was indexed by T-tau/Aβ42. Regional brain amyloid burden was quantified by Florbetapir PET. Sleep was evaluated with standard polysomnography (PSG) and with high density electroencephalography (EEG; 256 electrodes). After manual artifact removal (including EEG arousals), spectral analysis of Non-Rapid Eye Movement sleep was performed for all 256 channels (fast Fourier transform routine, Hanning window, 6s epochs). Topographic maps were then generated of the correlation between power in the slow wave range (1–4.5 Hz) and T-tau/Aβ42. Significant regional correlations were determined by statistical non-parametric mapping. Power was then extracted from the significant region, for further analyses with PET amyloid, controlling for age and time between CSF, PSG and PET collection. Higher CSF T-tau/Aβ42 was associated with a significant deficit in slow wave power in centro-parietal cortices. This SWA deficit was significantly associated with greater PET amyloid burden in the precuneus. Local reductions in sleep slow wave activity in brain regions affected early in AD are associated with elevated CSF and PET biomarker evidence of AD neuropathology. This relationship, in the absence of cognitive decline, suggests that loss of slow wave activity may contribute to early AD pathogenesis, and slow wave topography may itself represent a very early biomarker of AD.