Mild cognitive impairment and abnormal brain metabolic expression in idiopathic REM sleep behavior disorder

BackgroundMild cognitive impairment (MCI) is a common feature of isolated rapid-eye-movement sleep behavior disorder (iRBD). Here, we assessed cognitive functions and MCI in a prospective iRBD cohort and investigated their association with disease-specific brain metabolic patterns.MethodsForty-four patients with polysomnography-confirmed iRBD performed a standardized battery of neuropsychological examinations every two years. We used previously established spatial covariance patterns from de novo drug-naïve Parkinson's disease with concomitant RBD (_denovoPDRBD-RP) and iRBD (iRBD-RP) using ¹⁸F-fluorodeoxyglucose PET scan. We compared those expressions between iRBD with normal cognition (iRBD-NC) and with mild cognitive impairment (iRBD-MCI), and evaluated whether they predict progressive cognitive deterioration.ResultsTwenty iRBD patients (45 %) had MCI at baseline and 12 patients (27 %, about 7 % per year) had clinically significant cognitive deterioration after 4 years. The iRBD-MCI and iRBD-NC groups showed similar rates of cognitive change, but iRBD-MCI consistently performed worse in the domains of verbal memory and executive function. Elevated _denovoPDRBD-RP expression predicted cognitive deterioration (hazard ratio = 5.98 [1.70–21.06]), whereas iRBD-RP did not.ConclusionsIncreased disease-specific brain metabolic patterns are associated with iRBD-MCI and impending cognitive deterioration with the risk of progression to Lewy body dementia.     

Clinical and pathologic presentation in Parkinson's disease by apolipoprotein e4 allele status

BackgroundApolipoprotein (APOE) e4 allele status has been linked to clinical presentation and progression in Alzheimer's disease; however, evidence for a role of APOE e4 in Parkinson's disease (PD) remains largely inconclusive. In this analysis we explored potential significant associations between APOE e4 allele status and characteristics of clinical presentation in patients with PD.MethodsData came from 424 subjects evaluated using the Uniform Data Set (UDS) assessment collected by the National Alzheimer's Coordinating Center. Subjects had a known year of diagnosis of PD and experienced change in motor function prior to any change in cognition. Linear and logistic regression were used to model the association between APOE e4 carrier status and clinical characteristics including measures of cognitive decline and motor and neuropsychiatric symptoms. Amyloid burden was also evaluated for a subset of patients who died and consented to autopsy.ResultsOdds of dementia were higher in APOE e4 carriers (OR = 5.15), and, on average, APOE e4 carriers scored two points worse on tests of episodic memory and the Clinical Dementia Rating Sum of Boxes assessment. There was little evidence to support an association between e4 carrier status and severity of motor features, and, of the four neuropsychiatric symptoms evaluated, only presence of hallucinations was significantly associated with APOE e4 carrier status (OR = 5.29). Neuropathology data revealed higher frequencies of neuritic and diffuse amyloid plaques in APOE e4 carriers compared to non-carriers.ConclusionsAPOE e4 allele status is associated with dementia and severity of Alzheimer's disease pathologic features in PD.     

The apolipoprotein E epsilon4 allele and antidepressant efficacy in cognitively intact elderly depressed patients.

BACKGROUND: Patients vary in response to antidepressant medications. Apolipoprotein E (APOE) genotype affects vulnerability to stress and risk for cognitive impairment. We sought to determine if the APOE epsilon4 allele influences response in geriatric depression to mirtazapine and paroxetine, two frequently prescribed antidepressants. We hypothesized that epsilon4 carriers would show impaired antidepressant response. METHODS: The study was a double-blind, randomized, 8-week trial with a 16-week extension phase involving 246 cognitively intact patients aged 65 years or older with major depression. Patients were treated with mirtazapine 15-45 mg (n = 124) or paroxetine 20-40 mg (n = 122). The outcome measures were the Hamilton Depression Rating Scale, the Geriatric Depression Scale, and the Clinical Global Impression Scale. APOE genotype was determined by restriction isotyping. RESULTS: Patients carrying the epsilon4 allele showed a rapid onset of mirtazapine action, whereas paroxetine-treated patients with the epsilon4 allele were slow to respond. This difference could not be attributed to dosage, compliance, severity of adverse events, ethnicity, baseline depression or cognition, gender, or age. CONCLUSIONS: The APOE epsilon4 allele may affect antidepressant treatment outcome, but the effect depends on the medication. Further studies should determine if this result applies to other samples and medications.     

Cancer-related problems,sleep quality,and sleep disturbance among long-term cancer survivors at 9-years post diagnosis

ObjectiveTo estimate the prevalence of sleep difficulties in a large cohort of long-term cancer survivors (>5 years) and examine associations with four domains of cancer-related problems.MethodsThis study analyzed a nationwide sample (N = 1903) of cancer survivors (31% Breast; 20% prostate) at nine years (m = 8.9 sd = 0.6) post-diagnosis with a mean age of 64.5 years. Sleep quality and sleep disturbance were assessed by the Pittsburgh Sleep Quality Index. Multivariable logistic regression models examined associations between cancer-related problems (physical distress, emotional distress, economic distress, and fear of recurrence) and sleep difficulty (poor vs. low sleep quality and high vs. low sleep disturbance). Odds ratios (OR) and 95% confidence intervals (CI) were estimated, adjusting for medico-demographics, behavioral factors, and sleep medication use.ResultsIn sum, 20% percent of the sample reported poor sleep quality, 51% reported high sleep disturbance and 17% reported both. Sleep medication use was reported by 28% of the total sample. All four domains of cancer-related problems were significantly associated with poor sleep quality and high sleep disturbance. Above median cancer-related physical distress had the strongest association with both poor sleep quality (OR = 3.42; 95% CI = 2.44–4.79) and high sleep disturbance (OR = 4.06; 95% CI = 3.09–5.34).ConclusionsAmong nine-year cancer survivors, multiple domains of cancer-related health problems were associated with sleep difficulties. Knowledge of the relationship between cancer-related problems and sleep may aid clinicians during the evaluation and treatment of sleep problems in long-term cancer survivors. Future research should utilize prospective data to better understand the causal nature of the associations.     

A review of sleep disturbance in adults prescribed medications for opioid use disorder: potential treatment targets for a highly prevalent,chronic problem

BackgroundSleep disturbance in individuals prescribed medications for opioid use disorder (MOUD) is common, though the nature and progression of such concerns are difficult to discern due to differing terminology and assessment type between studies. Accurately identifying and treating sleep problems in this growing population has the potential to improve comorbidity and other MOUD outcomes.ObjectiveThe aim of the present review is to provide an overview of sleep in individuals stabilized on MOUD. Specifically, the following aspects of sleep were reviewed: 1) prevalence of clinically significant sleep disturbance; 2) sleep disturbance compared to findings in those not prescribed MOUD; 3) correlates of sleep disturbance; 4) self-reported sleep compared to objective measures.MethodStudies were identified using 6 large databases and included if they contained at least one measure of sleep during MOUD treatment as usual. Studies were excluded if they were case studies, not available in English, or participants were in withdrawal or detoxification.ResultsForty-two studies were included and categorized by type of sleep assessment: validated self-report questionnaire; provider-assessed; polysomnography; multi-method. Correlates were included if they were statistically significant (generally p < 0.05).ConclusionsThis review indicates there is a high prevalence of chronic self-reported sleep disturbance (eg, insomnia symptoms) in this population and suggests quantitative sleep parameters (eg, total sleep time) and respiratory problems during sleep are worse than in the general population. These sleep problems are correlated with psychiatric comorbidity and other substance use. Other correlates (eg, sociodemographic factors) require further study to draw definitive conclusions.     

Prevalence and correlates of mild cognitive impairment among diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging results

IntroductionWe estimated the prevalence and correlates of mild cognitive impairment (MCI) among middle-aged and older diverse Hispanics/Latinos.MethodsMiddle-aged and older diverse Hispanics/Latinos enrolled (n = 6377; 50–86 years) in this multisite prospective cohort study were evaluated for MCI using the National Institute on Aging–Alzheimer's Association diagnostic criteria.ResultsThe overall MCI prevalence was 9.8%, which varied between Hispanic/Latino groups. Older age, high cardiovascular disease (CVD) risk, and elevated depressive symptoms were significant correlates of MCI prevalence. Apolipoprotein E4 (APOE) and APOE2 were not significantly associated with MCI.DiscussionMCI prevalence varied among Hispanic/Latino backgrounds, but not as widely as reported in the previous studies. CVD risk and depressive symptoms were associated with increased MCI, whereas APOE4 was not, suggesting alternative etiologies for MCI among diverse Hispanics/Latinos. Our findings suggest that mitigating CVD risk factors may offer important pathways to understanding and reducing MCI and possibly dementia among diverse Hispanics/Latinos.     

Changes in the Initiation of Antipsychotics and Trazodone Over Time: A Cohort Study of New Admissions to Nursing Homes in Ontario,Canada

ObjectivesTo investigate whether trazodone is being initiated in lieu of antipsychotics following antipsychotic reduction efforts, this study described changes in medication initiation over time.MethodsWe conducted a retrospective cohort study of new admissions to nursing homes in Ontario, Canada between April 2010 and December 2019 using health administrative data (N = 61,068). The initiation of antipsychotic and trazodone use was compared by year of admission using discrete time survival analysis and stratified by history of dementia.ResultsRelative to residents admitted in 2014, antipsychotic initiation significantly decreased in later years (e.g., 2017 admission year hazard odds ratio [HOR₂₀₁₇]=0.72 [95% confidence interval (95%CI)=0.62–0.82]) while trazodone initiation modestly increased (e.g., HOR₂₀₁₇=1.09 [95%CI=0.98–1.21]). The relative increase in trazodone initiation was larger among residents with dementia (e.g., HOR_2017Dem =1.22 [95%CI=1.07–1.39]).ConclusionsDifferences in which medications were started following nursing home admission were observed and suggest trazodone may be initiated in lieu of antipsychotics.     

Association between dopaminergic medications and nocturnal sleep in early-stage Parkinson's disease

BackgroundPoor nocturnal sleep is common in Parkinson's disease (PD) and negatively impacts quality of life. There is little data on how dopaminergic drugs influence nocturnal sleep in PD, particularly in relation to medication timing. We examined the association between dopaminergic medications and subjective and objective nocturnal sleep in PD.MethodsIndividuals with PD were recruited from the outpatient clinic. Demographics and disease information were collected. Patients underwent one-night polysomnography and responded to SCOPA-SLEEP, a self-administered questionnaire which includes a section on nighttime sleep and an overall measure of sleep quality; higher scores indicate worse sleep. Medication intake, including medication timing in relation to bedtime, was obtained and converted to levodopa equivalents.Results41 Males and 21 females, median age 63.9 years, participated. Median disease duration was 5 years. After adjusting for age, sex, disease severity, and disease duration, greater total levodopa equivalent intake within 4 h of sleep was associated with higher total SCOPA-nighttime score (p = 0.009) and greater wake time after sleep onset (p = 0.049). Greater dopaminergic medication intake prior to sleep was also associated with less rapid eye movement (REM) sleep as a percent of total sleep time (p = 0.004).ConclusionsHigher amounts of dopaminergic medications taken prior to sleep were associated with poor sleep quality and less REM sleep. Although poor nocturnal sleep in PD is likely multi-factorial in etiology, our findings suggest that timing and dose of medications prior to sleep need to be considered in its management.     

The effect of sleep disturbance on social cognition in drug-naïve children with attention deficit and hyperactivity disorder

BackgroundA wide variety of psychiatric conditions are associated with social cognitive deficits. The relationship between social cognition and many factors, especially executive functions (EF), has been examined, but there is no study examining sleep and social cognition in children with attention deficit activity disorder (ADHD). It is important to find new approaches and intervention areas to improve their social cognitive skills. The main hypothesis of our study was that sleep disturbance would predict lower social cognition scores. We hypothesized that sleep disturbances and EF impairment could predict lower social cognitive performance.MethodsEighty-five children aged 7–12 years with drug-naïve ADHD were included in the study. Reading the Mind in the Eyes Test (RMET) and Faux Pas Recognition Test (FPRT) were used for social cognition performance; Stroop test was used for executive function performance. Sleep disturbance was evaluated with Children's Sleep Habits Questionnaire (CSHQ), ADHD severity with Conners Parent Rating Scale (CPRS). Hierarchical multiple regression analyses were performed to determine predictive factors of the FPRT and RMET.ResultsAge, gender, and comorbidity were included at step 1, CPRS-RS score was included at step 2, Stroop test part V score was included at step 3, CSHQ total score and sleep duration were included at step 4. Lower sleep disturbance score on CSHQ was associated with higher social cognition FPRT score (p = 0.014). There was no significant relationship between CSHQ and social cognition RMET score. Lower EF score on Stroop test part V was associated with higher social cognition FPRT score (p = 0.002) and higher social cognition RMET score (p < 0.001).ConclusionThese results showed that sleep disturbance and EF are both associated with social cognitive impairment, sleep particularly with the cognitive component. Identifying sleep problems in children with ADHD may provide helpful information in understanding and treating social cognitive impairments. This study is the first to draw attention to the relationship between sleep and social cognition.     

Electroencephalographic slowing heralds mild cognitive impairment in idiopathic REM sleep behavior disorder

ObjectivePatients with idiopathic rapid eye movement (REM) sleep behavior disorder (IRBD) may show electroencephalographic (EEG) slowing reflecting cortical dysfunction and are at risk for developing neurological conditions characterized by cognitive dysfunction including mild cognitive impairment (MCI), dementia with Lewy bodies and Parkinson’s disease with associated dementia. We hypothesized that those IRBD patients who later developed MCI had pronounced cortical EEG slowing at presentation.MethodsPower EEG spectral analysis was blindly quantified from the polysomnographic studies of 23 IRBD patients without cognitive complaints and 10 healthy controls without RBD. After a mean clinical follow-up of 2.40 ± 1.55 years, 10 patients developed MCI (RBD + MCI) and the remaining 13 remained idiopathic.ResultsPatients with RBD + MCI had marked EEG slowing (increased delta and theta activity) in central and occipital regions during wakefulness and REM sleep, particularly in the right hemisphere, when compared with controls and, to a lesser extent, with IRBD subjects who remained idiopathic. The EEG spectral pattern of the RBD + MCI group was similar to that seen in patients with dementia with Lewy bodies and Parkinson’s disease associated with dementia.ConclusionOur findings suggest that the presence of marked EEG slowing on spectral analysis might be indicative of the short-term development of MCI in patients initially diagnosed with IRBD.     

Age-related changes in slow wave activity rise time and NREM sleep EEG with and without zolpidem in healthy young and older adults

ObjectiveWhether there are age-related changes in slow wave activity (SWA) rise time, a marker of homeostatic sleep drive, is unknown. Additionally, although sleep medication use is highest among older adults, the quantitative electroencephalographic (EEG) profile of the most commonly prescribed sleep medication, zolpidem, in older adults is also unknown. We therefore quantified age-related and regional brain differences in sleep EEG with and without zolpidem.MethodsThirteen healthy young adults aged 21.9 ± 2.2 years and 12 healthy older adults aged 67.4 ± 4.2 years participated in a randomized, double-blind, within-subject study that compared placebo to 5 mg zolpidem.ResultsOlder adults showed a smaller rise in SWA and zolpidem increased age-related differences in SWA rise time such that age differences were observed earlier after latency to persistent sleep. Age-related differences in EEG power differed by brain region. Older, but not young, adults showed zolpidem-dependent reductions in theta and alpha frequencies. Zolpidem decreased stage 1 in older adults and did not alter other age-related sleep architecture parameters.ConclusionsSWA findings provide additional support for reduced homeostatic sleep drive or reduced ability to respond to sleep drive with age. Consequences of reduced power in theta and alpha frequencies in older adults remain to be elucidated.     

Psychosocial risk factors and Alzheimer's disease: the associative effect of depression,sleep disturbance,and anxiety

ABSTRACT

Objectives: Alzheimer's disease (AD) dementia is a neurodegenerative condition, which leads to impairments in memory. This study predicted that sleep disturbance, depression, and anxiety increase the hazard of AD, independently and as comorbid conditions.

Methods: Data from the National Alzheimer's Coordinating Center was used to analyze evaluations of 12,083 cognitively asymptomatic participants. Survival analysis was used to explore the longitudinal effect of depression, sleep disturbance, and anxiety as predictors of AD. The comorbid risk posed by depression in the last two years coupled with sleep disturbance, lifetime depression and sleep disturbance, clinician-verified depression and sleep disturbance, sleep disturbance and anxiety, depression in the last two years and anxiety, lifetime depression and anxiety, and clinician-verified depression and anxiety were also analyzed as predictors of AD through main effects and additive models.

Results: Main effects models demonstrated a strong hazard of AD development for those reporting depression, sleep disturbance, and anxiety as independent symptoms. The additive effect remained significant among comorbid presentations.

Conclusion: Findings suggest that sleep disturbance, depression, and anxiety are associated with AD development among cognitively asymptomatic participants. Decreasing the threat posed by psychological symptoms may be one avenue for possibly delaying onset of AD.     

Subclinical epileptiform activity during sleep in Alzheimer's disease and mild cognitive impairment

ObjectiveRecent findings suggested that subclinical epileptiform activity is prevalent during sleep in a significant proportion of Alzheimer’s Disease (AD) patients. The aims of our study were: (A) comparing the frequency of subclinical epileptiform activity during the sleep in a sample diagnosed with ‘probable’ AD and Mild Cognitive Impairment (MCI) due to AD, and in healthy subjects; (B) evaluating epileptiform EEG activity as a function of different sleep stages within a well-controlled polysomnographic setting.MethodsWe prospectively enrolled 50 ‘probable’ AD patients (73 ± 7.0 years) and 50 subjects with MCI due to AD (72 ± 6.7 years) without history of seizures, comparing them with 50 controls (69 ± 6.7 years). Patients underwent to a full-night video-PSG.ResultsSubclinical epileptiform activity was detected in 6.38% of ‘probable’ AD patients, 11.63% of MCI due to AD subjects and 4.54% of controls (p = 0.43). The comparisons between the three groups for the frequency of epileptiform activity did not reach statistically significant differences neither for total sleep nor for any sleep period considered.ConclusionsOur study shows that, when controlling for sleep stages and the influence of psychoactive drugs, AD patients and MCI due to AD subjects do not exhibit a higher frequency of epileptiform discharges during sleep compared to healthy subjects.SignificanceSubclinical epileptiform activity during sleep does not discriminate ‘probable’ AD from MCI due to AD and healthy controls.     

Associations between pain,objective sleep efficiency and cognition in patients with implantable cardioverter defibrillators

IntroductionPatients with implantable cardioverter defibrillators (ICDs) frequently experience sleep disruption. Prior work shows associations between objective (actigraphic) sleep and cognition in these patients, but whether pain affects associations between measures of sleep fragmentation (eg, sleep efficiency, SE) and cognition is unknown. The present study examined independent and interactive associations between objective SE and pain on cognitive performance in patients with ICDs.MethodsA total of 37 patients with ICDs (M_age = 60.0, SD = 12.4) and self-reported sleep disturbance completed 14 days of actigraphy. Average SE was computed [(average total sleep time/average time in bed) × 100%]. Patients completed the Short Form 36 Health Survey pain section, and computerized tasks measuring executive functioning (letter series, N-Back task), sustained attention/processing speed (symbol digit modalities test, SDMT), and simple reaction time. Multiple linear regressions examined whether SE independently predicted or interacted with pain ratings to predict cognitive performance.ResultsSE interacted with pain to predict SDMT performance, accounting for 12% unique variance. In patients reporting worse pain, higher SE was associated with better SDMT performance. Similar patterns of association on SDMT were not observed in patients with average or low pain. SE and pain ratings did not independently predict SDMT performance. Performance on other cognitive tasks was not associated with any predictors.ConclusionBetter sleep efficiency may play an important role in improving sustained attention/processing speed in patients with ICDs and perceived severe pain. Future research should examine whether interventions aimed at improving sleep fragmentation provide benefit to lower order cognition, particularly in patients with worse pain.     

Population-based cohort study on the increase in the risk for type 2 diabetes mellitus development from nonapnea sleep disorders

ObjectivesThe evidence concerning the relationship between nonapnea sleep disorders and the risk for type 2 diabetes mellitus (DM) is scant and elusive. Our study aimed to examine if nonapnea sleep disorders increase the risk for DM using a population-based retrospective cohort study from 1997 to 2010.MethodsIn the Taiwan’s National Health Insurance Research Database (NHIRD), 45,602 patients with nonapnea sleep disorders were identified as the study cohort. The comparison cohort was formed by 91,204 age- and gender-matched controls. Cox proportional hazards regression model was used to estimate the risk for developing DM.ResultsIn 45,602 patients with nonapnea sleep disorders, 7241 new cases of DM were reported during the follow-up period. The mean follow-up time was 9.04 (standard deviation [SD], 3.33) and 8.96 (SD, 3.47) for the nonapnea sleep disorders cohort and the comparison cohort, respectively. The incidence rate of DM was higher in the nonapnea sleep disorder cohort than in the comparison cohort (17.6 vs 13.3 per 1000 individuals-years). Overall, patients with nonapnea sleep disorders had a higher risk for DM compared to patients without nonapnea sleep disorders (adjusted hazard ratio [HR], 1.05 [95% confidence interval {CI}, 1.02–1.08]). Men with nonapnea sleep disorders had a higher risk for DM than the men in the comparison group (adjusted HR, 1.08 [95% CI, 1.03–1.14]). Among subjects aged less than 40 years, patients with nonapnea sleep disorders had a higher risk for DM than the comparison group (adjusted HR, 1.42 [95% CI, 1.27–1.59]). Compared with the comparison cohort, patients with sleep disturbance had an 11% higher risk for DM (adjusted HR, 1.11 [95% CI, 1.07–1.16]).ConclusionCompared to patients without nonapnea sleep disorders, patients with nonapnea sleep disorders had a higher risk for developing DM, especially among those who were less than 40 years of age and who had sleep disturbances.     

Pharmacological and non-pharmacological management of sleep disturbance in children: An Australian Paediatric Research Network survey

BackgroundAustralian paediatricians use a wide variety of practices when managing sleep disturbances in children, including use of melatonin and behavioral strategies. However, practice patterns around the use of strategies, dosing, and how the patient populations managed, are unknown. Results could inform guidelines for the management of child sleep disturbances.ObjectiveWe aimed to document management practices by Australian general paediatricians for paediatric sleep disturbances through an online survey sent to members of the Australian Paediatric Research Network (APRN) who are recruited from the Royal Australasian College of Physicians.Results181 (49%) of 373 eligible paediatricians responded, with 101 prescribing melatonin. The most commonly prescribed medications for poor sleep initiation were melatonin (89.1%), clonidine (48%) and antihistamines (29%). Melatonin doses ranged from 0.5 mg to 12 mg and duration of treatment was as long as 200 weeks. Less than half of the paediatricians were aware of any potential melatonin side effects. Most paediatricians (82%) reported using behavioral strategies for sleep disturbances, most commonly anxiety relaxation techniques (75%) for poor sleep initiation and graduated extinction (i.e. “controlled crying”, 52%) for disrupted overnight sleep.ConclusionsAustralian paediatricians use both pharmacological and non-pharmacological treatments for paediatric sleep disturbances. Melatonin is the most commonly prescribed medication, but wide variation in its prescribing suggests a lack of knowledge of recommended dosages and effectiveness. Given the prevalence and variation in prescribing, there is an urgent need to develop clear guidance for paediatricians managing children with sleep disturbance.     

Sleep and sadness: exploring the relation among sleep,cognitive control,and depressive symptoms in young adults

BackgroundSleep disturbance is a common feature of depression. However, recent work has found that individuals who are vulnerable to depression report poorer sleep quality compared to their low-risk counterparts, suggesting that sleep disturbance may precede depression. In addition, both sleep disturbance and depression are related to deficits in cognitive control processes. Thus we examined if poor sleep quality predicts subsequent increases in depressive symptoms and if levels of cognitive control mediated this relation.MethodsThirty-five undergraduate students participated in two experimental sessions separated by 3 weeks. Participants wore an actigraph watch between sessions, which provided an objective measure of sleep patterns. We assessed self-reported sleep quality and depressive symptoms at both sessions. Last, individuals completed an exogenous cuing task, which measured ability to disengage attention from neutral and negative stimuli during the second session.ResultsUsing path analyses, we found that both greater self-reported sleep difficulty and more objective sleep stability measures significantly predicted greater difficulty disengaging attention (i.e., less cognitive control) from negative stimuli. Less cognitive control over negative stimuli in turn predicted increased depression symptoms at the second session. Exploratory associations among the circadian locomotor output cycles kaput gene, CLOCK, single nucleotide polymorphism (SNP), rs11932595, as well as sleep assessments and depressive symptoms also are presented.ConclusionsThese preliminary results suggest that sleep disruptions may contribute to increases in depressive symptoms via their impact on cognitive control. Further, variation in the CLOCK gene may be associated with sleep quality.     

The APOE epsilon4 allele increases the risk of impaired spatial working memory in obstructive sleep apnea

BackgroundContradictory data have been published on the influence of Apolipoprotein E (APOE) ε4 allele on obstructive sleep apnea (OSA). The aims of this study were to confirm the presence of specific neuropsychological changes in OSA patients carrying the APOE ε4 allele and to clarify if these changes are due to the sole presence of this allele or to its interactions with OSA pathology.MethodsThe APOE genotype was examined in 123 patients with OSA and in 121 controls, together with a series of neuropsychological tests.ResultsOSA and control subjects had similar APOE genotype and allele distribution, but when neuropsychological tests were considered, OSA patients showed significantly lower values for verbal long-term (delayed free recall at the Rey auditory-verbal learning test) and working memory (bisyllabic words). Moreover, spatial span was found to be lower in OSA ε4 allele carriers than in non-carriers; this difference was not observed in controls.ConclusionsThis study confirms the presence of a verbal memory impairment in OSA patients and provides evidence for a significant interaction of APOE ε4 allele and OSA on frontal lobe function in adults, possibly mediated by the presence of specific frontal lobe neuroanatomical changes in these patients.     

Sleep/wake disruption in Alzheimer's disease: APOE status and longitudinal course

Disturbed sleep is a major clinical problem in Alzheimer's disease (AD). Apolipoprotein epsilon4 (APOE epsilon4) carrier status may increase risk of AD, yet there are no data on relations between APOE status and progression of sleep disturbance in AD. The objective of this study was to determine if sleep parameters in AD patients change over time as a function of APOE carrier status. Forty-four community-dwelling AD patients with diagnosis of probable AD were followed from early stages of disease. Their sleep/wake parameters were compared according to APOE status. For APOE epsilon4 carriers, only wake after sleep onset (WASO) increased in association with lower cognitive function as indicated by the Mini-Mental State Examination (MMSE); for non-epsilon4 subjects, increases in WASO and declines in total sleep time, sleep efficiency, and the amplitude of the rest/activity circadian rhythm over time were associated with lower performance on the MMSE. In these data, APOE status was associated with the progression of sleep/wake disturbances in AD. Overall, there was greater deterioration on sleep parameters in patients negative for the epsilon4 allele.     

The influence of job stress,social support and health status on intermittent and chronic sleep disturbance: an 8-year longitudinal analysis

ObjectiveTo determine the role of health status and social support in the relationship between job stress and sleep disturbance, for both intermittent and chronic sleep disturbance.MethodsA total of 1946 mid-life adults completed three questionnaires spanning an 8-year time frame. Sleep disturbance was assessed at each time point, and participants were classified as experiencing intermittent, chronic or no sleep disturbance across this 8-year period. Independent variables included a range of job stress measures, social support, physical and mental health, and demographic characteristics.ResultsAfter controlling for physical and mental health, perceived lack of job marketability increased risk of intermittent sleep disturbance (odds ratio (OR) = 1.33, p = 0.012). No other job stress measures were associated with either intermittent or chronic sleep disturbance after adjusting for years of education, social support, and employment status. Poorer mental and physical health status, although significantly increasing odds for intermittent sleep disturbance, represented a significantly greater increase in the odds for chronic sleep disturbance over and above intermittent disturbance (OR = 0.96, p < 0.001 for both SF-12 mental and physical health).ConclusionThis population-based cohort study found little evidence that job stress had an independent effect on chronic or intermittent sleep disturbance independent of health, social support, and education. Risk profiles for intermittent and chronic sleep disturbance did not differ with regard to job stress; however, various demographic and social support factors were distinguishing factors. Health status, both physical and mental, also showed a significantly greater impact on chronic sleep disturbance than intermittent sleep disturbance. Karasek’s model of job strain had little value in predicting sleep disturbance outcomes.