Mild cognitive impairment: associations with sleep disturbance, apolipoprotein e4, and sleep medications

Abstract

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.

Benzodiazepines and Related Drugs as a Risk Factor in Alzheimer's Disease Dementia

“…Thus, Burke et al investigated the role of anxiolytic drugs in the risk of AD. Likewise, they evaluated the association of APOE ε4, currently the most important risk factor in LOAD (Burke et al, 2018). One important finding of the study was that ε4 carriers had a statistically higher significant risk of AD development; however, this effect was moderated by the use of anxiolytics.…”

“…Sleep disturbances have been reported to increase Amyloid Beta (Aβ) levels in the cerebrospinal fluid of healthy subjects, contributing to the advancement of neurodegeneration and the appearance of mild cognitive impairment (MCI) (Lopez et al, 1999;Virta et al, 2007;Modabbernia et al, 2011;Consensus and Statements, 2014;Di Meco et al, 2014;Benedict et al, 2015;Gage et al, 2015;Chen et al, 2016;Gaugler et al, 2016;Kincheski et al, 2017;La Frenais et al, 2017;Livingston et al, 2017;Atkin et al, 2018;Burke et al, 2018). At preclinical level, it has been described that sleep deprivation in 3xTg mice acts as a chronic stressor, favoring the decrease of Cyclic adenosine monophosphate (cAMP) response element binding (CREB) and affecting synaptic plasticity and cognitive functions (Di Meco et al, 2014) (Figure 1).…”

Strategies for the use of Ginkgo biloba extract, EGb 761®, in the treatment and management of mild cognitive impairment in Asia: Expert consensus

“…Other interventions which may contribute to cognitive function include positive social activity 74,78‐80 and sleep management 81,82 …”

Time-Varying Insomnia Symptoms and Incidence of Cognitive Impairment and Dementia among Older US Adults

“…However, very little is known regarding the frequency or level of insomnia that would result in MCI and dementia. Published studies examining the associations between insomnia and MCI or dementia have predominantly assumed insomnia symptoms to be stagnant over time or have not considered the severity or type of insomnia symptoms [ 14 , 17 , 29 , 30 , 31 , 32 ]. These assumptions may be especially tenuous among older adult populations, as previous research shows that insomnia symptoms vary significantly over time and frequently increase as individuals get older [ 28 ].…”