APOE Genotype and Nonrespiratory Sleep Parameters in Cognitively Intact Older Adults

Spira, Adam P.; An, Yang; Yu, Peng; Wu, Mark N.; Simonsick, Eleanor M.; Ferrucci, Luigi; Resnick, Susan M.

doi:10.1093/sleep/zsx076

Cited by 18 publications

(13 citation statements)

References 43 publications

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“…Further, executive function and attention are significantly influenced by sleep abnormalities, which are prevalent in PTSD (Mohlenhoff, O'Donavan, Weiner, & Neylan, 2017). Recent studies have also demonstrated an association between APOE ε4 and disturbed sleep (Burke, Maramaldi, Cadet, & Kukull, 2016;Drogos et al, 2016;Spira et al, 2017).…”

Section: Discussionmentioning

confidence: 98%

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

et al. 2019

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Background Although the ε4 allele of the apolipoprotein E (APOE) gene and posttraumatic stress disorder (PTSD) have been linked to cognitive dysfunction and dementia risk, it is unknown whether they interact to predict cognitive dysfunction. Methods We analyzed data from European‐American (EA) veterans who participated in the National Health and Resilience in Veterans Study (NHRVS): main sample (n = 1,386) and primary replication sample (n = 509). EAs from the Yale–Penn Study cohort (n = 948) served as a second replication sample. Multivariable analyses were conducted to evaluate the predictive effects of ε4 carrier status and PTSD on cognitive functioning, with a focus on whether PTSD moderates the effect of ε4 carrier status. Results APOE ε4 allele carrier status (d = 0.15 and 0.17 in the main and primary replication NHRVS samples, respectively) and PTSD (d = 0.31 and 0.17, respectively) were independently associated with lower cognitive functioning. ε4 carriers with PTSD scored lower than those without PTSD (d = 0.68 and 1.29, respectively) with the most pronounced differences in executive function (d's = 0.75–1.50) and attention/concentration (d's = 0.62–1.33). A significant interaction was also observed in the Yale–Penn sample, with ε4 carriers with PTSD making more perseverative errors on a measure of executive function than those without PTSD (24.7% vs. 17.6%; d = 0.59). Conclusions APOE ε4 allele carriers with PTSD have substantially greater cognitive difficulties than ε4 carriers without PTSD. These results underscore the importance of assessing, monitoring, and treating PTSD in trauma‐affected individuals who are at genetic risk for cognitive decline and dementia.

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Section: Discussionmentioning

confidence: 98%

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

et al. 2019

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“…Surprisingly, very little evidence regarding APOE and sleep duration or other parameters characterizing sleep quality is available. The results of the Baltimore Longitudinal Study of Aging, which included 1264 participants without cognitive impairment, show that the ε4 allele of the APOE gene is associated with the increased probability of having short-sleep (OR = 1.41, 95% CI 1.06-1.88) but not with the sleep-onset or sleep-maintenance problems [43]. Intriguingly, very limited data confirm a relationship between melatonin, which is one of the major regulators of circadian rhythms, circadian genes, and APOE genetic variants [44][45][46], which presents a potential underlying mechanism of the relation between sleep duration and Lp(a) found in our study.…”

Section: Discussionmentioning

confidence: 99%

Sleep Duration, Lipid Profile and Insulin Resistance: Potential Role of Lipoprotein(a)

Korostovtseva

Alieva

Rotar

et al. 2020

IJMS

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Lipoprotein (a) (Lp(a)) is considered a genetic factor for cardiovascular disease playing an important role in atherogenesis and thrombosis, but the evidence about its association with sleep duration is controversial. We evaluated the relation between self-reported sleep duration and Lp(a). Among 1600 participants of the population-based sample, we selected 1427 subjects without previously known cardiovascular events, who answered the questions about their sleep duration; had valid lipid profile results (total cholesterol, low- and high-density lipoproteins, Lp(a), apolipoprotein AI (ApoAI), ApoB, and ApoB/ApoAI); and did not take lipid-lowering drugs (mean age 46 ± 12 years). We performed a structured interview, which included questions about lifestyle, medical history, complaints, and sleep duration (How long have you been sleeping per night during the last month?). Sleep duration was classified as follows: <6 h/night—short, 6–9 h/night—normal, and ≥10 h/night—long. Overall, 73 respondents (5.2%) were short-sleepers and 69 (4.8%) long-sleepers. Males were slightly more prevalent among short-sleepers. The groups matched by age, body mass index, blood pressure, diabetes mellitus, and hypertension rate. Short-sleepers had lower rates of high total cholesterol (≥5.0 mmol/L), lower Lp(a) levels and lower rates of increased Lp(a) ≥0.5 g/L, and higher insulin and insulin resistance (assessed by the homeostatic model assessment for insulin resistance (HOMA-IR)). ApoAI, ApoB, their ratio, and other lab tests were similar in the groups. The multinomial logistic regression demonstrated that only the short sleep duration was independently (odds ratio (OR) 0.29, 95% confidence interval (CI) (0.09–0.91), p = 0.033) associated with Lp(a) (χ2 = 41.58, p = 0.003). Other influencing factors were smoking and HOMA-IR. Such an association was not found for long-sleepers. In conclusion, a short-sleep duration is associated with Lp(a). The latter might mediate the higher insulin resistance and higher cardiometabolic risks in short-sleepers.

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“…After this step, all VIFs were below 2, which, based on Craney et al [46], enabled us to confidently proceed with our analyses. In Model 3, we controlled for ApoE gene status, in addition to age and sex, to determine if our results were independent of the ε4 genotype, which is associated with sleep disturbances [47,48]. We also performed follow-up analyses to determine if sleep-modifying medications contributed to the significant relationship between CC FA/MD and REM sleep.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…ApoE-ε4 carriers are at higher risk for cognitive decline than their non-ε4 counterparts [47]. Cognitive impairment is associated with reduced REM sleep and increased slow-wave sleep disturbances [48].…”

Section: Apoe Gene Status and Neural White Matter Healthmentioning

confidence: 99%

REM sleep is associated with white matter integrity in cognitively healthy, older adults

et al. 2020

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There is increasing awareness that self-reported sleep abnormalities are negatively associated with brain structure and function in older adults. Less is known, however, about how objectively measured sleep associates with brain structure. We objectively measured athome sleep to investigate how sleep architecture and sleep quality related to white matter microstructure in older adults. 43 cognitively normal, older adults underwent diffusion tensor imaging (DTI) and a sleep assessment within a six-month period. Participants completed the PSQI, a subjective measure of sleep quality, and used an at-home sleep recorder (Zeo, Inc.) to measure total sleep time (TST), sleep efficiency (SE), and percent time in light sleep (LS), deep sleep (DS), and REM sleep (RS). Multiple regressions predicted fractional anisotropy (FA) and mean diffusivity (MD) of the corpus callosum as a function of total PSQI score, TST, SE, and percent of time spent in each sleep stage, controlling for age and sex. Greater percent time spent in RS was significantly associated with higher FA (β = 0.41, p = 0.007) and lower MD (β =-0.30, p = 0.03). Total PSQI score, TST, SE, and time spent in LS or DS were not significantly associated with FA or MD (p>0.13). Percent time spent in REM sleep, but not quantity of light and deep sleep or subjective/objective measures of sleep quality, positively predicted white matter microstructure integrity. Our results highlight an important link between REM sleep and brain health that has the potential to improve sleep interventions in the elderly.

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APOE Genotype and Nonrespiratory Sleep Parameters in Cognitively Intact Older Adults

Abstract: Self-reported sleep duration, napping, and trouble falling/staying asleep differ by APOE genotype. Studies are needed to examine whether APOE promotes AD by degrading sleep and to clarify the role of race in these associations.

Cited by 18 publications

References 43 publications

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

Apolipoprotein E gene polymorphism, posttraumatic stress disorder, and cognitive function in older U.S. veterans: Results from the National Health and Resilience in Veterans Study

Sleep Duration, Lipid Profile and Insulin Resistance: Potential Role of Lipoprotein(a)

REM sleep is associated with white matter integrity in cognitively healthy, older adults

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