Associations between period 3 gene polymorphisms and sleep- /chronotype-related variables in patients with late-life insomnia.

A variable number tandem repeat polymorphism (VNTR) in the period 3 (PER3) gene has been associated with heritable sleep and circadian variables, including self-rated chronotypes, polysomnographic (PSG) variables, insomnia and circadian sleep-wake disorders. This report describes novel molecular and clinical analyses of PER3 VNTR polymorphisms to better define their functional consequences. As the PER3 VNTR is located in the exonic (protein coding) region of PER3, we initially investigated whether both alleles (variants) are transcribed into messenger RNA in human fibroblasts. The VNTR showed bi-allelic gene expression. We next investigated genetic associations in relation to clinical variables in 274 older adult Caucasian individuals. Independent variables included genotypes for the PER3 VNTR as well as a representative set of single nucleotide polymorphisms (SNPs) that tag common variants at the PER3 locus (linkage disequilibrium (LD) between genetic variants < 0.5). In order to comprehensively evaluate variables analyzed individually in prior analyses, dependent measures included PSG total sleep time and sleep latency, self-rated chronotype, estimated with the Composite Scale (CS), and lifestyle regularity, estimated using the social rhythm metric (SRM). Initially, genetic polymorphisms were individually analyzed in relation to each outcome variable using analysis of variance (ANOVA). Nominally significant associations were further tested using regression analyses that incorporated individual ANOVA-associated DNA variants as potential predictors and each of the selected sleep/circadian variables as outcomes. The covariates included age, gender, body mass index and an index of medical co-morbidity. Significant genetic associations with the VNTR were not detected with the sleep or circadian variables. Nominally significant associations were detected between SNP rs1012477 and CS scores (p = 0.003) and between rs10462021 and SRM (p = 0.047); rs11579477 and average delta power (p = 0.043) (analyses uncorrected for multiple comparisons). In conclusion, alleles of the VNTR are expressed at the transcript level and may have a functional effect in cells expressing the PER3 gene. PER3 polymorphisms had a modest impact on selected sleep/circadian variables in our sample, suggesting that PER3 is associated with sleep and circadian function beyond VNTR polymorphisms. Further replicate analyses in larger, independent samples are recommended.

Task switching in older adults with and without insomnia.

BACKGROUND: Task-switching deficits are common in older adults and in those with insomnia. Such deficits may be driven by difficulties with sleep continuity and dampened homeostatic sleep drive. OBJECTIVE: To identify the aspects of task switching affected by insomnia and its treatment, and to determine whether such effects are associated with sleep continuity and homeostatic sleep drive. METHODS: Polysomnographic sleep and task switching were tested in healthy older adults aged 60-93 years with insomnia (n = 48) and normal sleeping controls (n = 51). Assessments were repeated in the insomnia group after eight weeks of cognitive behavioral treatment for insomnia. Sleep measures included wake after sleep onset (WASO) and quantitative indices of homeostatic sleep drive (delta power during nonrapid eye movement [NREM] sleep and the ratio of delta power during the first and second NREM periods). A cued task-switching paradigm instructed participants to perform one of two tasks with varying preparatory cue-target intervals, manipulating task alternation, task repetition, and task preparation. RESULTS: The effect of preparatory cues on accuracy was diminished in the insomnia group compared with that in controls. Across the two groups, a stronger effect of preparatory cues was associated with a higher delta sleep ratio. Following insomnia treatment, task-repetition accuracy significantly improved. This improvement was associated with improvements in WASO. There were no group or treatment effects on response time or task alternation accuracy. CONCLUSIONS: Effects of insomnia diagnosis and treatment apply to conditions that depend on the maintenance of a task set, rather than a domain general effect across task switching. Such effects are associated with homeostatic sleep drive and sleep continuity.

Changes in Cognitive Performance Are Associated with Changes in Sleep in Older Adults With Insomnia.

The present study examined sleep features associated with cognition in older adults and examined whether sleep changes following insomnia treatment were associated with cognitive improvements. Polysomnography and cognition (recall, working memory, and reasoning) were assessed before and after an insomnia intervention (Brief Behavioral Treatment of Insomnia [BBTI] or information control [IC]) in 77 older adults with insomnia. Baseline wake-after-sleep-onset (WASO) was associated with recall. Greater NREM (nonrapid eye movement) delta power and lower NREM sigma power were associated with greater working memory and reasoning. The insomnia intervention did not improve performance. However, increased absolute delta power and decreased relative sigma power were associated with improved reasoning. Findings suggest that improvements in executive function may occur with changes in NREM architecture.

Arabic versions of the sleep timing questionnaire and the composite scale of morningness.

OBJECTIVES: To develop Arabic versions of English language questionnaires to estimate morningness/eveningness and sleep variables. METHODS: We translated the Composite scale of morningness (CSM) and the sleep timing questionnaire (STQ) [with added siesta questions] into Arabic; the Arabic versions were then back translated. The revised Arabic and the original English versions were next administered to bi-lingual Egyptians using a crossover design (n=25). The Arabic versions of both scales were subsequently administered to an independent Egyptian sample (n=79) and the siesta variables examined in relation to the CSM. RESULTS: Satisfactory correlations were present between the English and Arabic versions for total CSM scores (Spearman's ρ=0.90, p<0.001). All but one of the STQ variables were significantly correlated (Spearman's ρ=0.45-0.88, p≤0.05). In the Arabic version, the frequency of siesta naps per week was significantly correlated with the total CSM score, with evening types taking more naps (Spearman's ρ=-0.23, p≤0.05). CONCLUSIONS: Arabic versions of the STQ and CSM have been developed in Egypt, and are freely available. They can be used for behavioral research related to sleep and circadian function and can be adapted for use in other Arab speaking populations.

Subjective-objective sleep discrepancy among older adults: associations with insomnia diagnosis and insomnia treatment.

Discrepancy between subjective and objective measures of sleep is associated with insomnia and increasing age. Cognitive behavioural therapy for insomnia improves sleep quality and decreases subjective-objective sleep discrepancy. This study describes differences between older adults with insomnia and controls in sleep discrepancy, and tests the hypothesis that reduced sleep discrepancy following cognitive behavioural therapy for insomnia correlates with the magnitude of symptom improvement reported by older adults with insomnia. Participants were 63 adults >60 years of age with insomnia, and 51 controls. At baseline, participants completed sleep diaries for 7 days while wearing wrist actigraphs. After receiving cognitive behavioural therapy for insomnia, insomnia patients repeated this sleep assessment. Sleep discrepancy variables were calculated by subtracting actigraphic sleep onset latency and wake after sleep onset from respective self-reported estimates, pre- and post-treatment. Mean level and night-to-night variability in sleep discrepancy were investigated. Baseline sleep discrepancies were compared between groups. Pre-post-treatment changes in Insomnia Severity Index score and sleep discrepancy variables were investigated within older adults with insomnia. Sleep discrepancy was significantly greater and more variable across nights in older adults with insomnia than controls, P ≤ 0.001 for all. Treatment with cognitive behavioural therapy for insomnia was associated with significant reduction in the Insomnia Severity Index score that correlated with changes in mean level and night-to-night variability in wake after sleep onset discrepancy, P < 0.001 for all. Study of sleep discrepancy patterns may guide more targeted treatments for late-life insomnia.

Behavioral treatment of chronic insomnia in older adults: does nocturia matter?

OBJECTIVE: To evaluate the impact of nocturia on the therapeutic response of chronic insomnia to behavioral treatment in older adults. METHODS: Secondary analysis of a randomized clinical trial designed to assess the efficacy of brief behavioral treatment of insomnia (BBTI) vs. an information-only control (IC) in 79 community-dwelling older adults with chronic insomnia. For the current analysis, participants were stratified into 2 groups: those with self-reported nocturia at baseline i.e., ≥ 1 void/night (N = 30; 16 IC, 14 BBTI) and those without nocturia (N = 49; 24 IC, 25 BBTI). We then determined the impact of BBTI on sleep, sleep quality, and nocturia as assessed by self-report, actigraphy, and polysomnography. RESULTS: Individuals without baseline nocturia responded well to BBTI with significant decrease in sleep latency, wake after sleep onset, and total sleep time assessed by sleep diary and actigraphy; these changes were significantly greater than those in the IC group. In comparison, changes in the same sleep parameters among participants with nocturia were not significantly different from the IC control. Although BBTI showed significant improvement in sleep quality in groups with and without nocturia (as assessed by PSQI and sleep diary), the effect size of these improvements was larger in those without nocturia than in those with nocturia (PSQI d = 0.82 vs. 0.53, diary sleep quality d = 0.83 vs. 0.51). CONCLUSIONS: These secondary analyses suggest that brief behavioral treatment of insomnia may be more efficacious in improving insomnia in participants without nocturia. Addressing nocturia may improve the efficacy of behavioral insomnia treatment.

Can a function-based therapy for spousally bereaved seniors accrue benefits in both functional and emotional domains?

Late-life spousal bereavement has detrimental effects in daily functioning and emotional distress. This study tested the hypothesis that a therapy based exclusively upon functioning issues (sleep and daily lifestyle regularity) would accrue benefits in both functional and emotional domains. A comparison was made with a control therapy that concentrated on emotional issues, and specifically avoided discussing sleep or lifestyle regularity. Thirty-eight spousally bereaved seniors were randomly assigned to either functional or control therapy. Assessments were made before, during, and after a 6-month, 10-session individual therapy. The functional therapy assisted in both functional and emotional domains and the hypothesis was confirmed.

Chronotype, bed timing and total sleep time in seniors.

Many older adults (seniors) experience problems with getting enough sleep. Because of the link between sleep and circadian rhythms, changes in bedtime lead to changes in the amount of sleep obtained. Although primarily determined genetically, chronotype changes with advancing age towards a more morning-type (M-type) orientation. In a 2006 study, we have found a linear relationship, by which the earlier a senior's bedtime, the more sleep she/he will obtain. The aim of this study was to see whether this relationship differs for M-type seniors, as compared to seniors outside the M-type category. Retired seniors (n = 954, 535 M, 410F, 65 years+, mean age 74.4 years) taking part in a telephone interview were divided into M-types and Other types (O-types) using the Composite Scale of Morningness (CSM). The relationship between bedtime and Total Sleep Time (TST), and between rise-time and TST, was tested using linear regression separately for M-types and O-types. For each participant, habitual bedtime, rise-time and total Sleep Time (TST) [after removing time spent in unwanted wakefulness] were obtained using a telephone version of the Sleep Timing Questionnaire (STQ). Both chronotype groups showed a significant linear relationship between bedtime and TST (p < 0.001); with earlier bedtimes leading to more TST (M-type 5.6 min; O-type 4.4 min per 10 min change [slope difference p = 0.05]); and an opposite relationship between rise-time and TST with earlier rise-times leading to less TST (M-type 6.7 min; O-type 4.2 min per 10 min change [slope difference p = 0.001]). M-types retired to bed 56 min earlier (p < 0.001), awoke 93 min earlier (p < 0.001) and obtained 23 min less TST (p < 0.001) than O-types. In conclusion, both chronotypes showed TST to be related in a linear way to bedtime and rise-time; the overall shorter TST in M-types was due to them rising 93 min earlier, but only retiring to bed 56 min earlier than O-types; as well as having a steeper rise-time versus TST relationship.

Behavioral treatment of insomnia: also effective for nocturia.

OBJECTIVES: To evaluate changes in self-reported nocturia in community-dwelling adults aged 60 and older who received behavioral treatment for chronic insomnia. DESIGN: Secondary analysis of a randomized controlled trial of a behavioral intervention for sleep. SETTING: Academic medical center. PARTICIPANTS: Of the 79 enrollees, this analysis focused on 30 who, in addition to insomnia, also reported at least one nightly episode of waking up to void. INTERVENTION: The brief behavioral treatment of insomnia (BBTI) group (n = 14) received instructions on reducing time in bed and setting a regular sleep schedule. The information control (IC) group (n = 16) received printed materials. A nurse clinician delivered both interventions. MEASUREMENTS: Self-reported nocturnal awakenings to void assessed daily for 14 days at baseline and 4 weeks after the intervention. Participants who reported at least one episode of nocturia per night at baseline were included in this analysis. RESULTS: In individuals with nocturia at baseline, the total number of nocturnal voids over the 14-day assessment period decreased by 6.5 ± 4.8 in the BBTI group and increased by 1.3 ± 7.3 in the IC group (P = .04, effect size 0.82). After adjusting for baseline nocturia episodes, the difference remained significant (P = .05). CONCLUSION: In older adults with concurrent insomnia and nocturia, behavioral treatment directed solely at insomnia may also improve self-reported nocturia. Behavioral treatment of insomnia should be further investigated for its effect on nocturia in individuals with concurrent insomnia and nocturia.

A Hindi version of the Composite Scale of Morningness.

BACKGROUND: Several pen and paper measures of human circadian preference are available in English, but none are available in Hindi, hampering research in circadian behavior among Hindi speaking populations in India and elsewhere. The present study describes a Hindi version of the Composite Scale of Morningness (CSM), a self-reported questionnaire widely used to assess morningness/eveningness (M/E). M/E has been used a proxy for circadian phase in lieu of cumbersome and expensive laboratory studies. METHOD: The thirteen item English version of the CSM was translated into Hindi and independently back translated into English. Inconsistencies between the original and back translated versions were then resolved. Both versions were next administered to bilingual persons at Delhi, India (N=130). After intra-class correlations between the Hindi and the English versions were examined, the Hindi version was administered to community based participants representing different age groups (N=310). RESULTS: There was satisfactory intra-class correlation (ICC) between the total scores for the Hindi and the English versions of the CSM (Cronbach's alpha=0.873), with variation for individual items scores. Total CSM scores in the second sample suggested a significant association with age, consistent with published reports with the English CSM, i.e., morningness tendencies were more likely to be reported by older adults. Significant associations with gender or educational status were not observed. CONCLUSIONS: The Hindi CSM is a brief questionnaire that provides behavioral measures of diurnal preference. It is freely available for research in Hindi speaking populations.

Exposure to shift work as a risk factor for diabetes.

Using telephone survey data from 1111 retired older adults (≥65 years; 634 male, 477 female), we tested the hypothesis that exposure to shift work might result in increased self-reported diabetes. Five shift work exposure bins were considered: 0 years, 1-7 years, 8-14 years, 15-20 years, and >20 years. Shift work exposed groups showed an increased proportion of self-reported diabetes (χ(2) = 22.32, p < 0.001), with odds ratios (ORs) of about 2 when compared to the 0-year group. The effect remained significant after adjusting for gender and body mass index (BMI) (OR ≥ 1.4; χ(2) = 10.78, p < 0.05). There was a significant shift work exposure effect on BMI (χ(2) = 80.70, p < 0.001) but no significant gender effect (χ(2) = 0.37, p > 0.50).

Polysomnographic Sleep and Circadian Temperature Rhythms as a Function of Prior Shift Work Exposure in Retired Seniors.

In an earlier published telephone interview study (n > 1,000) we have shown that retired shift workers subjectively report worse sleep than retired day workers. This laboratory study sought to determine whether these findings held up when objective polysomnograhic (PSG) measures of sleep were taken and whether retirees' circadian temperature rhythms differed as a function of shift work exposure. All completers of the telephone interview were invited to attend a 36-hour laboratory study for which participants were paid. This involved continuous core body temperature measurement (using an ingestible pill-based system) and 2 nights of PSG. Shift work exposure (plus other measures) was collected by taking a detailed work history. The second laboratory night was scored into sleep stages. Post hoc, we divided participants into 4 shift work exposure groups: 0 years (ie, no exposure to shift work), 1 to 7 years, 7 to 20 years, and >20 years. Sample sizes were 11, 16, 15, and 15, respectively, with approximate equality in mean age (71.7 years of age, 69.1 years of age, 70.0 years of age, and 70.4 years of age, respectively) and percent male (63%, 50%, 67%, and 73%, respectively). Shift work exposure was associated with worse PSG sleep in a dose-related fashion. The percentages of participants with sleep efficiency, 80% for the 0 years, 1 to 7 years, 7 to 20 years, and >20 years groups were 36%, 63%, 67%, and 73%, respectively (P < 0.01), and the percentages with total sleep time (TST), 6 hours were 36%, 56%, 53%, and 73%, respectively (P < 0.01). From the circadian rhythm record, shift work exposure appeared to result (P = 0.06) in an increased spread of phase angles (difference between habitual bedtime and time of temperature trough). In conclusion, it appears likely that shift work may be related to a scarring of sleep and circadian rhythms. This may be associated with a change in the relationship between habitual sleep timing and the phase of the circadian pacemaker.

Depression in the spousally bereaved elderly: correlations with subjective sleep measures.

Complaints of poor sleep and symptoms of depression are likely to coexist in the spousally bereaved elderly. This study was concerned with the correlation between depressive symptoms and various measures of subjectively reported sleep using questionnaire and diary instruments in 38 bereaved seniors (60y+). Correlations between the sleep measures and days since loss and grief intensity were also calculated. All sleep disruption measures correlated significantly with depression score, but only sleep duration correlated with grief intensity, and no sleep measure correlated with days since loss. Therapies which address both sleep and depression are likely to be of benefit to bereaved seniors.

A quantitative approach to distinguishing older adults with insomnia from good sleeper controls.

STUDY OBJECTIVE: Establishing quantitative criteria to distinguish individuals with and without insomnia is important for clinical and research applications, but consensus has not yet been reached for specific values. The purpose of this study was to identify the optimal quantitative thresholds for actigraphy and sleep diary that differentiate older adults (> 60 years) with insomnia from good sleeper controls. METHODS: A total of 119 participants (79 insomnia [35% male], 40 control [31.7% male]; mean age = 71.7 [7.2] years) completed at least 7 nights of sleep diary and actigraphy. Receiver operating characteristic curve analyses and the Youden index were used to identify optimal threshold values. Outcomes for each measurement method included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency (SE), and total sleep time (TST). RESULTS: Sleep diary measures produced areas under the curves (AUC) in the high range (0.84-0.97), whereas actigraphy performed poorly at discriminating the two groups (AUC 0.58-0.61). The Youden index identified SOL = 18 minutes, WASO = 21 minutes, SE = 92%, and TST = 388 minutes as the sleep diary measures that yielded the highest sensitivity and specificity values for insomnia-control discrimination. Accounting for hypnotic medication and sleep apnea use did not change the findings. CONCLUSION: Sleep diary parameters discriminated individuals with insomnia from good sleepers more accurately than actigraphy. These quantitative criteria are similar to those reported by other investigators using different methods and samples, including younger adults. The results suggest that the sleep diary, an inexpensive self-report sleep measure, may be used in clinical and research settings to help distinguish older adults with and without insomnia.

Shiftworkers report worse sleep than day workers, even in retirement.

The aim of this study was to explore how the level of shiftwork exposure during an individual's working life might be related to subjectively reported sleep quality and timing during retirement. Telephone interviews regarding past employment and sleep timing and quality (among other variables) were conducted using a pseudo-random age-targeted sampling process. Subjective sleep quality was assessed using a telephone version of the Pittsburgh Sleep Quality Index. Timing of reported habitual bedtimes and rise-times were assessed using the Sleep Timing Questionnaire. Questions measuring morningness and subjective health were also given. Retired seniors (aged >65 years, n = 1113) were studied. Analysis was by analysis of variance, with shiftwork exposure in three bins [0 (n = 387), 1-15 (n = 371) and >15 years (n = 355)], gender (n = 634 male, 479 female) and former occupation [in two broad categories, 'managerial' (n = 437) versus 'other' (n = 676)] as factors. In retired shiftworkers, relative to retired day workers, past exposure to shiftwork was associated with higher (worse) PSQI scores by 1.0 units (1-15 years) and 0.6 units (>15 years) (main effect P = 0.005). There were also main effects of gender and former occupation (males and managerials reporting better sleep), but neither variable interacted with shiftwork exposure. The timing of current mean habitual bedtimes and rise-times (and also the variance around them) were very similar for the three shiftwork exposure groups. The shiftwork exposure effect did not appear to be mediated by either morningness or current health. Prior exposure to shiftwork would appear to be related to currently reported sleep problems during retirement.

Dream content in complicated grief: a window into loss-related cognitive schemas.

Bereavement and its accompanying psychological response (grief) constitute potent experiences that necessitate the reorganization of cognitive-affective representations of lost significant attachment figures during both wakefulness and dreaming. The goals of this preliminary study were to explore whether the dream content of 77 adults with complicated grief (CG) differed from that of a normative sample and whether CG patients who dream of the deceased differ from CG patients who do not dream of the deceased on measures of daytime emotional distress. CG dreams were characterized by more family and familiar characters including the deceased (in women), and fewer social interactions and emotions compared to norms. Increased representations of familiar characters in CG dreams may reflect attempts to reorganize relational cognitive schemas to compensate for the loss.

Timing, Duration and Quality of sleep, and Level of Daytime sleepiness in 1166 Retired seniors.

A telephone survey of 1166 community resident seniors (658 male, 508 female, age between 65 and 97 years, mean 74.8 years) was undertaken, which included among other components telephone versions of the Pittsburgh Sleep Quality Index (PSQI), the Epworth Sleepiness Scale (ESS), and the Sleep Timing Questionnaire (STQ). The median PSQI score was 5 and the median ESS score 6, suggesting that neither sleep problems, nor daytime sleepiness problems, were particularly prevalent in this sample of seniors. The STQ indicated that the habitual timing of the sleep episode appeared to be within the usual 11 pm to 7:30 am range, with about 7.5 hours of actual sleep within that interval being reported. There was, however, a sizable minority who broke this pattern, with 25% of the sample reporting less than 6.7 hours of sleep, and problems with nocturnal sleep and daytime sleepiness.

Circadian preference and sleep-wake regularity: associations with self-report sleep parameters in daytime-working adults.

The aim of this study was to explore how interindividual differences in circadian type (morningness) and sleep timing regularity might be related to subjective sleep quality and quantity. Self-report circadian phase preference, sleep timing, sleep quality, and sleep duration were assessed in a sample of 62 day-working adults (33.9% male, age 23?48 yrs). The Pittsburgh Sleep Quality Index (PSQI) measured subjective sleep quality and the Sleep Timing Questionnaire (STQ) assessed habitual sleep latency and minutes awake after sleep onset. The duration, timing, and stability of sleep were assessed using the STQ separately for work-week nights (Sunday?Thursday) and for weekend nights (Friday and Saturday). Morningness-eveningness was assessed using the Composite Scale of Morningness (CSM). Daytime sleepiness was measured using the Epworth Sleepiness Scale (ESS). A morning-type orientation was associated with longer weekly sleep duration, better subjective sleep quality, and shorter sleep-onset latency. Stable weekday rise-time correlated with better self-reported sleep quality and shorter sleep-onset latency. A more regular weekend bedtime was associated with a shorter sleep latency. A more stable weekend rise-time was related to longer weekday sleep duration and lower daytime sleepiness. Increased overall regularity in rise-time was associated with better subjective sleep quality, shorter sleep-onset latency, and higher weekday sleep efficiency. Finally, a morning orientation was related to increased regularity in both bedtimes and rise-times. In conclusion, in daytime workers, a morning-type orientation and more stable sleep timing are associated with better subjective sleep quality. (Author correspondence: asoehner@berkeley.edu ).

A Neurobiological Model of Insomnia.

Insomnia is a common clinical condition resulting in significant costs and morbidity. Previous models of insomnia focusing on psychological and behavioral processes are useful clinically, but lack neurobiological specificity. We propose an insomnia model based on basic and clinical neuroscience findings, and hypothesize that insomnia results from persistent activity in wake-promoting neural structures during NREM sleep. The simultaneous occurrence of sleeping and waking neural activity helps to explain clinical phenomenology and treatment effects in insomnia.