This study examined biological sex differences in the development of mild cognitive impairment (MCI) and probable Alzheimer's disease (AD) development as predicted by changes in the hippocampus or white matter hyperintensities. A secondary data analysis of the National Alzheimer's Coordinating Center Uniform Data Set was conducted. We selected samples of participants with normal cognition at baseline who progressed to MCI (n = 483) and those who progressed to probable AD (n = 211) to determine if hippocampal volume or white matter hyperintensities (WMH) at baseline predicted progression to probable AD or MCI and whether the rate of progression differed between men and women. The survival analyses indicated that changes in hippocampal volumes affected the progression to probable AD (HR = 0.535, 95% CI [0.300-0.953]) only among women. White men had an increased rate of progression to AD (HR = 4.396, CI [1.012-19.08]; HR = 4.665, 95% CI [1.072-20.29]) compared to men in other race and ethnic groups. Among women, increases in hippocampal volume ratio led to decreased rates of progressing to MCI (HR = 0.386, 95% CI [0.166-0.901]). Increased WMH among men led to faster progression to MCI (HR = 1.048. 95% CI [1.011-1.086]). Women and men who were older at baseline were more likely to progress to MCI. In addition, results from longitudinal analyses showed that women with a higher CDR global score, older age at baseline, or more disinhibition symptoms experienced higher odds of MCI development. Changes in hippocampal volumes affect the progression to or odds of probable AD (and MCI) more so among women than men, while changes in WMH affected the progression to MCI only among men.

Objective: Mild cognitive impairment (MCI) is associated with increased memory problems although the ability to complete daily life activities remains relatively intact. This study examined: (1) if sleep disturbance increased the hazard of MCI; (2) if APOE e4 carriers with sleep disturbance experience an increased risk of MCI; and, (3) if prescription sleep medications provide a protective effect against MCI. We hypothesized that sleep disturbance increases the hazard of MCI, this relationship is stronger among APOE e4 carriers reporting a sleep disturbance. Furthermore, we hypothesized that sleep medications decrease the hazard of MCI. Methods: To determine whether sleep medication mediates the risk of developing MCI for individuals with sleep disturbance and/or APOE e4, we analyzed the National Alzheimer’s Coordinating Center Uniform Data Set. We selected participants with normal cognition at baseline (n = 6798), and conduced survival analyses. Results: Our main findings indicated that the hazard of MCI was significantly associated with sleep disturbance. The hazard remained among those who did not use sleep medication. Trazodone and zolpidem users did not have a significant hazard of MCI, but the significant hazard remained for those who did not use these medications. APOE e4 carriers had a significantly higher hazard of MCI. Among e4 carriers who used trazodone or zolpidem, there was not a statistically significant risk of MCI. Conclusion: This study demonstrated the potential utilization of trazodone and zolpidem in the treatment of sleep disturbance while potentially mitigating the risk of MCI. While trazodone and zolpidem have been shown to positively impact sleep disturbance in individuals with normal cognition, further research should explore these findings given that these medications are potentially inappropriate for older adults.

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Cost-sharing increases due to specialty tier-level cost sharing were associated with interruptions in MS and RA specialty drug treatments.