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SLEEP DISORDERED BREATHING, APOE4 AND β-AMYLOID DEPOSITION IN COGNITIVELY NORMAL ELDERLY

      Background

      Sleep Disordered Breathing (SDB) is commonly reported in the elderly, and recent studies in humans and animals describe associations between SDB and Alzheimer disease (AD). ApoE4 allele is considered the most important risk factor for sporadic AD. We examined whether SDB is associated with changes in amyloid burden in a sample of cognitively normal elderly. The interactive effect of SDB*APOE4 on amyloid burden was also examined.

      Methods

      Data used were obtained from the ADNI database (adni.loni.usc.edu). Study participants included a total of 516 cognitively normal subjects and were a subset of the ADNI cohort. SDB was self-reported and participants were labeled SDB+, or SDB−. Brain Aβ-42 levels were determined at baseline and follow-up visits. Multi-level mixed effects linear regression models were used to examine the relationship between SDB and Aβ-42 volumes. First, we fit a linear regression model for each participant separately at each time point, and second, we regressed unknown time-specific regression coefficients against time. Our models were adjusted for sex, and body mass index. There was no difference between OSA groups for APOE e4 status, age and history of cardiovascular disease. The interactive effect of SDB*APOE4 on amyloid burden was also examined.

      Results

      There was significant variation between subjects in mean Aβ-42 volumes at baseline (intercept) (mean SUVR; B = 0.006, p > .0001), as well as significant variation in the change in Aβ-42 volumes over time (slope) (mean SUVR; B = 0.006, p > .0001). The covariance between the baseline Aβ-42 level and Aβ-42 volume change over time indicated that SDB subjects experienced a faster increase in brain Aβ-42 volumes over time (p > .0001). The interactive effect of SDB*APOE4 on amyloid burden was not significant.

      Conclusions

      Among community-dwelling cognitively normal older adults, SDB is associated with greater β-amyloid burden changes over time regardless of APOE4 status. This suggests that clinical interventions aimed at SDB, such as treatment with CPAP or dental appliances, implemented during the early phase in which tissue damage precedes clinical symptoms and neuronal dysfunction, may mitigate the progression of cognitive impairment.