Despite the widespread use of cART, cognitive impairment continues to be a prevalent concern in both symptomatic and asymptomatic individuals with chronic HIV infection.1 The relationship between sleep and cognitive performance assessed by comprehensive neuropsychological and sleep function evaluation in an HIV cohort has not been previously reported. Our results suggest that both subjective and objective indices of sleep continuity and quality may have a significant relationship with cognitive performance in HIV-positive individuals.
Furthermore, many participants demonstrated patterns strongly suggestive of chronic partial sleep deprivation, which may be the result of behaviorally induced insufficient sleep syndrome.42 According to the International Classification of Sleep Disorders-2 classification, the key diagnostic features of this syndrome refer to an individual who reports customary sleep times (at home during their “normal routine”) measured by history, sleep diary, or actigraphy which is significantly shorter than the sleep time recorded when placed in a noncustomary setting (eg, PSG in sleep research facility). Due to this self-imposed chronic partial sleep debt, when the individual is provided an ad libitum sleep opportunity in a research facility (despite the unfamiliar environment and cumbersome recording techniques), he or she will often show “supra” efficient sleep architectural patterns, including very high sleep efficiency, markedly short sleep onset latency, and minimal sleep fragmentation on PSG. Similar to the patterns characterized by those with behaviorally induced insufficient sleep syndrome, many of the individuals in our cohort demonstrated markedly reduced sleep latencies of <10 minutes with sleep efficiencies often greater than 90% on their PSGs. In turn, many of these same participants demonstrated significantly shorter sleep durations on their 2-week home monitoring compared with their PSG and much shorter durations than the recommended 7.5–8.5 hours needed for most adults to function optimally. Study participants demonstrating patterns suggestive of chronic partial sleep deprivation reported more complaints of daytime sleepiness and performed significantly poorer on several measures of cognitive function compared with participants without these suggestive patterns.
Interestingly, self-reported daytime sleepiness, based on the ESS, was significantly higher in the cognitively unimpaired group (using Frascati criteria) than in the impaired group. The ESS inquires about the likelihood of “dozing” in specific scenarios, such as while in a movie theatre or meeting or while driving. Because most of our cohort was not actively employed and did not own an automobile, these scenarios may not have occurred customarily enough for our cohort to accurately respond. Based on our findings, future studies evaluating the relationship between sleep and cognition amongst HIV-positive individuals should consider the participant’s historical sleep behaviors, attitudes, daily habits, and relevant sociodemographic factors (ie, employment and residential status, common means of transportation).
Some studies have suggested that demographics, such as female gender, age, low body mass index, and history of intravenous drug use, may increase the risk for future cognitive impairment in seropositive individuals. Overall, health status may also be a potential issue, with 2 large longitudinal cohort studies (the Central Nervous System HIV Antiretroviral Therapy Effects Research and MACS) reporting increased risk for HAND development in aviremic subjects who suffered with “incidental” comorbidities (examples include low reading level, school problems, brain trauma, history of cerebrovascular events, epilepsy, central nervous system opportunistic diseases, major depression, psychotic disorder, and substance abuse) compared with aviremic participants without these comorbidities.1,3
Obtaining ideal sleep quality and quantity is another critical component for both optimal cognitive performance and immune function.43 HIV enters the brain early after infection, and disturbances in sleep patterns during the asymptomatic stage of HIV infection were recognized and reported very early in the HIV/AIDS epidemic.44 The release of cytokines including monocyte chemoattractant protein-1 (CCL2), tumor necrosis factor alpha, interleukin (IL) 1 beta, IL-6, interferon gamma, and IL-15 in the brain is thought to lead to neuronal injury and dysfunction45 and has recently been correlated with the development of HAND.46,47 In addition, many of these same cytokines such as tumor necrosis factor alpha, IL-1, and interferon alpha can modulate sleep wake patterns and can be associated with significant sleep architectural changes.48–50 Studies are warranted to look at the effect of sleep loss on central nervous system immune activity, especially because there is evidence to suggest that sleep disruption can increase blood–brain barrier permeability for proinflammatory substances.1,51,52 Thus, identification of the sleep wake patterns and disturbances specific to HIV-positive individuals may prove fertile in furthering our understanding of HAND manifestation and suggest future preventative and therapeutic avenues.
Although this study yielded several important findings, its ability to detect subtle cognitive differences based on a 4-tiered Frascati classification may have been limited by its relatively small sample size. Conducting this type of study utilizing multimethod sleep assessments and observations across several time points requires an inordinate amount of financial and personnel resources. Even though our study sample of predominantly black males may place limits on generalizability, CDC statistics continue to show that black males are disproportionately affected by HIV as compared with other demographic groups.53 Significantly lower mean sleep durations have also been reported for black men compared with other demographic groups in general population studies,53 and similar sleep behavioral patterns suggestive of self-imposed chronic partial sleep deprivation were also revealed in our cohort. Providing counseling on the importance of adequate sleep opportunity may prove to be an effective health care management strategy. Although HIV-positive individuals undergoing treatment with efavirenz were excluded in this study to minimize confounding medication-related effects on sleep,54,55 evidence regarding the impact of efavirenz on sleep is mixed with some reports actually demonstrating no significant difference in sleep disturbance among individuals on efavirenz compared with other cART regimens.4,56 Moreover, even among the studies reporting an association between sleep disruption and efavirenz, the findings ranged from significant changes in sleep architecture in some studies although others may have only found significant differences in reports of “unusual dream.”57,58 With the wide prevalence of efavirenz use in modern cART, future studies may consider including those undergoing treatment with efavirenz to provide further insight and generalizability. Thus, we anticipate that the findings revealed in this study will serve as additional support for conducting future and larger-scale studies to evaluate the relationship between sleep and cognition across multiple demographic groups living with HIV and undergoing varying cART regimens.
Even in the context of optimally controlled viral replication (low or undetectable viral loads), patients may still continue to experience mild or asymptomatic forms of neurocognitive dysfunction at a surprisingly high rate.59 The stringent inclusion criteria and intricate protocol employed in this study certainly biased toward the inclusion of subjects who were more stable cognitively. However, individuals demonstrating even milder forms of impairment such as ANI are at higher risk for eventual progression to more severe forms of HAND.3 Moreover, deficits sufficient to impact activities of daily living that are essential for disease management, including medication adherence, have been shown in seropositive individuals, especially those younger than 50 years, regardless of their level of cognitive impairment.60 Thus, identifying confounding factors, such as sleep disturbances that might influence the manifestation of neurocognitive impairment, is critical in the post-cART era.
The authors acknowledge Dr Adam Spira for his invaluable contributions to this project.
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