Sonia Ancoli-israel | University of California, San Diego (original) (raw)

Papers by Sonia Ancoli-israel

Journal Of Clinical Psychopharmacology, 1990

This article contains the sleep results of the efficacy study of flurazepam 30 mg and 15 mg, mida... more This article contains the sleep results of the efficacy study of flurazepam 30 mg and 15 mg, midazolam 15 mg, and placebo in the 99 chronic insomniacs studied as part of this multicenter study. After a 20-day drug washout, all-night sleep was recorded on 2 baseline nights, on the first 2 treatment nights, on treatment night 7, and on the last 2 nights of the study (nights 13 and 14). To reduce the number of comparisons, electroencephalographic (EEG) sleep latency, EEG wake time, EEG sleep efficiency, post-sleep questionnaire (PSQ) sleep latency, and PSQ total sleep were preselected as the major sleep variables. Between-groups comparisons indicated that, when compared with the placebo control, all drugs improved sleep, but differences were statistically significant only for the first 2 nights, i.e., the early interval. Midazolam was more effective than either dose level of flurazepam on treatment night 1. Within-group analyses indicated that all drug groups showed significantly improved sleep from baseline throughout drug administration, but the placebo group did not significantly improve from baseline by either objective or subjective measures at any of the three time intervals. The sleep of patients taking flurazepam 30 mg did not differ significantly from the sleep of those receiving the 15 mg dose for any of the five major sleep variables at any interval. Objective EEG and subjective PSQ sleep variables showed significant positive correlations.

The Journals of Gerontology, Oct 1, 2004

Background. Older adults with dementia often have disruptions in circadian rhythms, including dis... more Background. Older adults with dementia often have disruptions in circadian rhythms, including disruptions of the restactivity rhythm. These disruptions are a product of internal neuronal activity and external environmental influences, both of which are deficient in dementia. However, the consequences of disturbed rhythms are unknown. This study examined the relationship between rest-activity rhythms and death in patients with dementia. Methods. The authors recruited 149 older adults with dementia (104 women; mean age, 84.1 years) from nursing homes. Activity was recorded with wrist actigraphs from each participant for 3 days. Survival was determined by examining public death records. Cox proportional hazards models were used to determine which aspects of rest-activity rhythms were related to survival. Results. The timing of each participant's rest-activity rhythm compared with a sample of persons without dementia was related to survival, such that those who more closely resembled the persons without dementia lived longer. Conclusions. Although rest-activity rhythms as a whole were not related to survival, the timing of the rhythm was. Patients with dementia appear to develop an abnormal timing of their rhythms, which is predictive of shorter survival. It may be possible to intervene with these patients to correct the timing of their rhythms and possibly prolong their lives.

Journal of the American Geriatrics Society, Nov 1, 2009

MPH-study concept and design, acquisition of data, analysis and interpretation of data, preparati... more MPH-study concept and design, acquisition of data, analysis and interpretation of data, preparation of manuscript Terri L. Blackwell, MA-analysis and interpretation of data, critical review of manuscript Susan Redline, MD-analysis and interpretation of data, critical review of manuscript Sonia Ancoli-Israel, PhD-analysis and interpretation of data, critical review of manuscript Misti L. Paudel, MPH-analysis and interpretation of data, critical review of manuscript Peggy M. Cawthon, PhD-analysis and interpretation of data, critical review of manuscript Thuy-Tien Dam, MD-analysis and interpretation of data, critical review of manuscript Elizabeth Barrett-Connor, MD-analysis and interpretation of data, acquisition of data, critical review of manuscript Ping C. Leung, MD-analysis and interpretation of data, critical review of manuscript Katie L. Stone, PhD-study concept and design, acquisition of data, analysis and interpretation of data, critical review of manuscript Statistical Analysis: Ms. Terri Blackwell performed the statistical analyses and is independent of any commercial funder. She had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analyses. Sponsor's Role: The funding agencies had no direct role in the conduct of the study; the collection, management, analyses and interpretation of the data; or preparation or approval of the manuscript. Other Contributions: We would like to thank Mr. Kyle A. Moen for his assistance with the manuscript and preparation and formatting of the tables.

Chronobiology International, Mar 31, 2011

Prior studies have suggested an increased risk of CVD-related mortality in older adults with dist... more Prior studies have suggested an increased risk of CVD-related mortality in older adults with disturbed circadian rest/activity rhythms (RARs). The objective goal of this study was to examine the association between disrupted RARs and risk of cardiovascular disease (CVD) events in older men. A total of 2,968 men aged 67 yrs and older wore wrist actigraphs for 115±18 consecutive hours. RAR parameters were computed from wrist actigraphy data and expressed as quartiles (Q). CVD events consisted of a composite outcome of coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD) events. Secondary analyses examined associations between RARs and individual components of the composite outcome (CHD, stroke, and PVD). There were 490 CVD events over an average of 4.0±1.2 yrs. Overall, reduced amplitude (HR = 1.31, 95%CI 1.01-1.71 for Q2 vs. Q4) and greater minimum (HR = 1.33, 95%CI 1.01-1.73 for Q4 vs. Q1) were associated with an increased risk of CVD events in multivariable-adjusted models. In secondary analyses, there was an independent association between reduced amplitude (HR = 1.36, 95%CI 1.00-1.86) and greater minimum activity counts (HR = 1.39, 95%CI 1.02-1.91) with increased risk of CHD events. Reduced F-value (HR = 2.88, 95%CI 1.41-5.87 for Q1 vs. Q4 and HR = 2.71, 95%CI 1.34-5.48 for Q2 vs. Q4) and later occurring acrophase of the RAR (HR = 1.65, 95%CI 1.04-2.63 for Q4 vs. Q2-3) were associated with an increased risk of PVD events. Results were similar in men without a history of CVD events. The findings revealed among older men, measures of decreased circadian activity rhythm robustness (reduced amplitude and greater minimum activity) were associated with an increased risk of CVD events, primarily through increased risk of CHD or stroke events, whereas measures of reduced circadian activity rhythm robustness were not associated with risk of CVD events overall, but were associated with an increased risk of PVD events. These results should be confirmed in other populations.

Biological Psychiatry, Jun 1, 1999

Background: Since the prevalence of both sleep-disordered breathing (SDB) and periodic limb movem... more Background: Since the prevalence of both sleep-disordered breathing (SDB) and periodic limb movements in sleep (PLMS) increase with age, we explored whether older schizophrenia patients would have a high incidence of SDB and PLMS. Correlations between sleep and clinical variables were also examined. Methods: Fifty-two patients (mean age ϭ 59.6 years, SD ϭ 8.9) had their sleep/wake, respiration, and leg movements recorded using a modified Medilog/Respitrace portable recording system plus oximetry. A battery of clinical, psychosocial, and motor disturbance variables were collected by research center staff. Results: Forty-eight percent of these patients had at least 10 respiratory events per hour of sleep. These patients reported more symptoms of daytime sleepiness than patients with fewer than 10 events per hour. The relatively high prevalence of SDB in this group may contribute to overall sleep disturbances, and does not appear to be a result of high body mass index. Only 14% of the patients had at least five limb movements per hour of sleep, suggesting the prevalence of PLMS is much lower than expected in this age group. The number of leg jerks was inversely related to symptoms of tardive dyskinesia. Conclusions: The disturbance of sleep in these patients may be due, in part, to SDB, but is unlikely due to PLMS.

Journal of Psychiatric Research, May 1, 2005

Patient reports and laboratory studies suggest schizophrenia patients have disrupted sleep across... more Patient reports and laboratory studies suggest schizophrenia patients have disrupted sleep across age groups. Studies have not compared overall sleep/wake patterns or circadian (24-h) activity rhythms of older community dwelling schizophrenia patients to matched comparison subjects. This study examined whether older schizophrenia patients had more disrupted sleep/wake patterns and circadian activity rhythms than age-and gender-matched normal comparison subjects (NCS). Twenty-eight older schizophrenia patients and 28 age-and gender-matched NCS were studied with three days of continuous wrist actigraphy. Nighttime and daytime actigraphically estimated sleep and wake, circadian activity rhythms and light exposure patterns were compared with and without years of education as a covariate. Patients spent longer in bed, had more disrupted nighttime sleep, slept more during the day, and had less robust circadian rhythms of activity and light exposure compared to NCS. Differences persisted in education-adjusted analyses. Within patients, working was associated with improved sleep and circadian rhythms. Findings suggest the sleep and circadian rhythm disruption of older schizophrenia patients was more extensive than that of matched NCS suggesting patientsÕ sleep disruption was above and beyond what is attributable to advanced age alone. A need exists to develop multicomponent interventions to address sleep difficulties specific to older schizophrenia patients.

Alzheimers & Dementia, Jul 1, 2018

95%CI: 1.14, 2.72, p1⁄4 0.02) compared to OSA-/Ab+ subjects. Being OSA+/Abdid not reveal signific... more 95%CI: 1.14, 2.72, p1⁄4 0.02) compared to OSA-/Ab+ subjects. Being OSA+/Abdid not reveal significant differences in time-to-progression from MCI to AD when compared to OSA-/Absubjects (aHR) 1⁄4 1.17, 95% CI: 0.86, 1.48, p 1⁄4 0.07). Conclusions:Among MCI patients, brain amyloid levels may modify the relationship between OSA and AD. Furthermore OSA+ subjects maybe more physiologically susceptible to Ab load at certain threshold levels.

PubMed, Sep 1, 1999

Older adults frequently experience difficulties with sleep that can be caused by specific sleep d... more Older adults frequently experience difficulties with sleep that can be caused by specific sleep disorders (such as sleep-disordered breathing or periodic limb movements in sleep) and circadian rhythm disturbances. These all can be effectively treated. Medical illnesses and medications also can have a negative affect on sleep and effective management of these can significantly improve sleep in older adults. Sleep in institutionalized older adults is even more disturbed than sleep of community-dwelling older people and special considerations can be made to improve the quality of sleep in institutional settings.

Chronobiology International, Nov 23, 2015

Activity rhythm disturbances and depression often co-occur among older adults. However, little is... more Activity rhythm disturbances and depression often co-occur among older adults. However, little is known about how activity rhythm disturbances themselves co-occur, or how disturbances to multiple aspects of the activity rhythm relate to depression over time. In this study, we performed a Latent Class Analysis to derive subgroups of older men [total n ¼ 2933, mean age ¼ 76.28, standard deviation (SD) ¼ 5.48] who shared similar patterns of activity rhythm disturbances (defined as extreme values of modeled activity rhythm parameters). We found eight subgroups with distinct combinations of activity rhythm disturbances: one had all normative activity rhythm parameters (32.09%), one had only lower activity (10.06%), three had earlier activity (totaling 26.96%) and three had later activity (totaling 30.89%). Groups with similar timing were distinguished depending on whether the relative length of the active period was shorter and/or if the activity rhythm had lesser amplitude/robustness. We next examined whether the derived activity rhythm subgroups were associated with different rates of change in depression symptom levels over an average of 5.5 (0.52 SD) follow-up years. The subgroup with lower activity only had faster increases in depressive symptoms over time (compared with the group with normative rhythm parameters), but this association was accounted for by adjustments for concurrently assessed health status covariates. Independent of these covariates, we found that four activity rhythm disturbance subgroups experienced faster depressive symptom increases (compared with the normative subgroup): These included all three subgroups that had later activity timing and one subgroup that had earlier activity timing plus a shorter active period and a dampened rhythm. Low activity rhythm height/ robustness with normal timing therefore may mark depression risk that is attributable to co-occurring disease processes; in contrast, having late or combined early/compressed/dampened activity rhythms may independently contribute to depression symptom development. Our findings suggest that activity rhythm-related depression risk is heterogeneous, and may be detected when multiple aspects of rhythm timing are delayed or when early timing is accompanied by compressed/dampened activity rhythms. Future studies should consider how distinct combinations of altered activity rhythm timing and height/robustness develop and conjointly determine health risks. Further research is also needed to determine whether/how activity rhythms can be modified to improve depression outcomes.

Psychosomatic Medicine, 2019

Objective Older adults are among the most frequent users of emergency departments (EDs). Nonspeci... more Objective Older adults are among the most frequent users of emergency departments (EDs). Nonspecific symptoms, such as fatigue and widespread pain, are among the most common symptoms in patients admitted at the ED. Interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) are inflammation biomarkers associated with chronic stress (i.e., dementia caregiving) and nonspecific symptoms. This study aimed to determine whether IL-6 and TNF-α were prospectively associated with ED risk in dementia caregivers (CGs). Methods Participants were 85 dementia CGs, who reported during three assessments (3, 9, and 15 months after enrollment) if they had visited an ED for any reason. Cox proportional hazards models were used to examine the relations between resting circulating levels of IL-6 and TNF-α obtained at enrollment and subsequent risk for an ED visit, adjusting for age, sex, use of ED 1 month before enrollment, physical and mental health well-being, body mass index, and CG demands. Results (lo...

BMC Geriatrics, 2019

Background: Caregivers of a family member with a chronic disability or illness such as dementia a... more Background: Caregivers of a family member with a chronic disability or illness such as dementia are at increased risk for chronic disease. There are many factors that contribute to dementia caregiver vulnerability and these factors can be challenging to assess in clinical settings. Self-rated health (SRH) is an independent measure of survival and physical health in the elderly. As an inclusive measure of health, SRH has been proposed as a reliable way to assess a patient's general health in primary care. Therefore, we sought to identify determinants of poor/fair SRH versus categories of at least good SRH in informal caregivers. Methods: In a cross-sectional study, we examined 134 elderly (≥55 years) providing in-home care for a spouse with dementia who rated their own health with a single-item question: "In general, would you say your health is excellent, very good, good, fair or poor?". In a multivariable model, we compared caregivers with poor/fair SRH to those with good, very good, or excellent SRH on demographics, health characteristics (health behaviors, physical health indicators, psychosocial factors) and caregiving-specific stress (a composite index/total of four caregivingspecific stressors: years of caregiving, dementia severity, care recipient functional impairment and perceived caregiver burden). Results: Compared with caregivers who rated their own health as either good (31.3%), very good (38.8%) or excellent (14.2%), caregivers with poor/fair SRH (15.7%) were more likely to have lower physical function and total greater caregiving-specific stress. More years of caregiving, severe dementia and care recipient functional impairment, but not perceived caregiver burden, were also more likely among caregivers with poor/fair SRH. Additionally, high negative affect and low positive affect were more likely in caregivers with poor/fair vs. good or excellent and very good or excellent SRH, respectively. Conclusions: Caregivers with poor/fair SRH were characterized by higher levels of medical comorbidity, low physical function, high negative, but low positive affect and longer duration of caregiving, as well as more severe dementia and greater functional impairment of the care recipient. These findings suggest that caregivers need to be more closely evaluated and targeted for preventive interventions in clinical practice. Trial Registration: ClinicalTrials.gov registration number: NCT02317523.

Journal of the American Geriatrics Society, 2018

ObjectiveTo examine rest–activity circadian rhythm (RAR) and cognitive decline in older men.Desig... more ObjectiveTo examine rest–activity circadian rhythm (RAR) and cognitive decline in older men.DesignLongitudinal.SettingOsteoporotic Fractures in Men (MrOS) and ancillary Outcomes of Sleep Disorders in Men (MrOS Sleep) studies.ParticipantsMrOS and MrOS Sleep participants (N=2,754; mean age 76.0 ± 5.3).MeasurementsThe Modified Mini‐Mental State examination (3MS) was used to assess cognition at baseline (2003–05) and follow‐up examinations (2005–06 and 2007–09). Wrist actigraphy was used to measure 24‐hour activity counts at baseline. RAR variables included amplitude (strength of activity rhythm), mesor (mean activity level), pseudo F‐statistic (overall circadian rhythm robustness), and acrophase (time of daily peak activity).ResultsAfter an average of 3.4 ± 0.5 years, men with lower amplitudes, mesors, and pseudo F‐statistics had greater decline in 3MS performance (amplitude: –0.7 points Q1 vs –0.5 points Q4, p<.001; mesor: –0.5 points Q1 vs –0.2 points Q4, p=.01; pseudo F‐statistic...

Sleep, 2001

Study Objectives: Some, but not all, researchers report that obstructive sleep apnea (OSA) patien... more Study Objectives: Some, but not all, researchers report that obstructive sleep apnea (OSA) patients experience increased depressive symptoms. Many psychological symptoms of OSA are explained in part by other OSA comorbidities (age, hypertension, body mass). People who use more passive and less active coping report more depressive symptoms. We examined relationships between coping and depressive symptoms in OSA. Setting: N/A Design/Participants: 64 OSA (respiratory disturbance index (RDI)≥15) patients were studied with polysomnography and completed Ways of Coping (WC), Profile of Mood States (POMS), Center for Epidemiological Studies-Depression (CESD) scales. WC was consolidated into Approach (active) and Avoidance (passive) factors. Data were analyzed using SPSS 9.0 regression with CESD as the dependent variable and WC Approach and Avoidance as the independent variables. Interventions: N/A Measurements and Results: WC Approach factor (B=-1.105, ß=-.317, p=.009) was negatively correlated and WC Avoidance factor (B=1.353, ß=.376, p=.007) was positively correlated with CESD scores. These factors explained an additional 8% of CESD variance (p<.001) beyond that explained by the covariates: demographic variables, RDI, and fatigue (as measured by the POMS). Conclusions: More passive and less active coping was associated with more depressive symptoms in OSA patients. The extent of depression experienced by OSA patients may not be due solely to effects of OSA itself. Choice of coping strategies may help determine who will experience more depressive symptoms.

Sleep, 1997

We measured 24-hour circadian-rhythm patterns of activity and sleep/wake activity in a group of n... more We measured 24-hour circadian-rhythm patterns of activity and sleep/wake activity in a group of nursing-home patients (58 women and 19 men with a mean age of 85.7 years). Severely demented patients were contrasted with a composite group of moderately, mild, or not-demented patients. Sleep/wake activity and light exposure were recorded with the Actillume recorder. Cosinor analyses were computed to determine the mesor, amplitude, acrophase, and circadian quotient of the activity rhythms. The diagnosis of dementia was based on the Mini Mental Examination and on examination of medical records. Sleep was extremely fragmented in both groups of nursing-home patients. Severely demented patients slept more both at night and during the day, but there were no significant differences in the number of awakenings during the night or in the number of naps during the day when compared to the composite group of moderate, mild, or no-dementia patients. The severely demented group had lower activity mesor, more blunted amplitude, and were more phase delayed (i.e. had later acrophases) than the other group. In addition, the severely demented patients spent less time exposed to bright light. These results confirm that circadian rhythms in nursing-home patients are disturbed with more disturbance in the severely demented. Much of the disturbance may be related not just to age but to mental status.

Psychosomatic Medicine, 2016

Objectives To evaluate whether objectively measured sleep characteristics are associated with mor... more Objectives To evaluate whether objectively measured sleep characteristics are associated with mortality risk independent of inflammatory burden and comorbidity. Methods The Osteoporotic Fractures in Men Sleep Study (conducted in 2003–2005) included community-dwelling older men (n = 2531; average [standard deviation {SD}] age = 76.3 (5.5) years). Sleep measures from in-home polysomnography and wrist actigraphy and assessments of serum inflammatory markers levels (C-reactive protein, interleukin-6, tumor necrosis factor α, tumor necrosis factor α soluble receptor II, and interferon-γ) were obtained. Vital status was ascertained over an average (SD) follow-up of 7.4 (1.9 SD) years. Results Three of the seven main sleep measures examined were independently associated with greater inflammatory burden. Mortality risk associated with prolonged (≥10% total sleep time) blood oxygen desaturation and short (<5 hours) sleep duration was attenuated to nonsignificance after adjusting for infla...

Springer eBooks, 1999

It is well known that patients with psychiatric disorders complain of sleep difficulties and, in ... more It is well known that patients with psychiatric disorders complain of sleep difficulties and, in fact, these complaints are confirmed by objective studies.1 Patients with schizophrenia and patients with mood disorders tend to have extremely disturbed sleep and complain of excessive daytime sleepiness, insomnia, or both. There is some evidence that patients with schizophrenia may have circadian rhythm disturbances and/or blunted circadian sleep/wake patterns.2-4 It is known that light exposure is a strong synchronizer of the sleep/wake system and that exposure to bright light tends to decrease with advancing age5 In addition to its direct effect on the circadian system, light exposure has also been implicated as a treatment for some mood disorders.

Stress (Amsterdam, Netherlands), 2012

The stress associated with providing care for a spouse diagnosed with Alzheimer's disease can... more The stress associated with providing care for a spouse diagnosed with Alzheimer's disease can have adverse effects on cardiovascular health. One potential explanation is that chronic caregiving stress may contribute to the development of atherosclerosis. The purpose of this study was to determine whether the duration that one has provided care is associated with the degree of atherosclerotic burden, as measured by carotid artery intima-media thickness (IMT). One hundred and ten Alzheimer caregivers [mean age 74 ± 8 (SD) years, 69% female] underwent in-home assessment of carotid artery IMT via B-mode ultrasonography. Data regarding medical history, blood pressure, and multiple indicators of caregiving stress were also collected. Multiple regression indicated that duration of care was positively associated with IMT measured in the internal/bifurcation segments of the carotid artery (β = 0.202, p = 0.044) independent of risk factors such as age, gender, body mass index, smoking his...

Fatigue: Biomedicine, Health & Behavior, 2013

Background-Breast cancer (BC) patients often experience cancer-related fatigue (CRF) before, duri... more Background-Breast cancer (BC) patients often experience cancer-related fatigue (CRF) before, during, and after their chemotherapy. Circadian rhythms are 24-hour cycles of behavior and physiology that are generated by internal pacemakers and entrained by zeitgebers (e.g., light). A few studies have suggested a relationship between fatigue and circadian rhythms in some clinical populations. Methods-One hundred and forty-eight women diagnosed with stage I-III breast cancer and scheduled to receive at least four cycles of adjuvant or neoadjuvant chemotherapy, and 61 controls (cancer-free healthy women) participated in this study. Data were collected before (Baseline) and after four cycles of chemotherapy (Cycle-4). Fatigue was assessed with the Short Form of Multidimensional Fatigue Symptom Inventory (MFSI-SF); circadian activity rhythm (CAR) was recorded with wrist actigraphy (six parameters included: amplitude, acrophase, mesor, up-mesor, down-mesor and F-statistic). A mixed model analysis was used to examine changes in fatigue and CAR parameters compared to controls, and to examine the longitudinal relationship between fatigue and CAR parameters in BC patients. Results-More severe CRF (total and subscale scores) and disrupted CAR (amplitude, mesor and F-statistic) were observed in BC patients compared to controls at both Baseline and Cycle-4 (all p's<0.05); BC patients also experienced more fatigue and decreased amplitude and mesor, as well as delayed up-mesor time at Cycle-4 compared to Baseline (all p's<0.05). The increased total MFSI-SF scores were significantly associated with decreased amplitude, mesor and F-statistic (all p's<0.006). Conclusion-CRF exists and CAR is disrupted even before the start of chemotherapy. The significant relationship between CRF and CAR indicate possible underlying connections. Reentraining the disturbed CAR using effective interventions such as bright light therapy might also improve CRF.

Psychiatry Research, 2008

Caring for a spouse with Alzheimer's disease (AD) is associated with overall health decline and i... more Caring for a spouse with Alzheimer's disease (AD) is associated with overall health decline and impaired cardiovascular functioning. This morbidity may be related to the effects of caregiving stress and impaired coping on β 2-adrenergic receptors, which mediate hemodynamic and vascular responses and are important for peripheral blood mononuclear cell (PBMC) trafficking and cytokine production. This study investigated the longitudinal relationship between stress, personal mastery, and β 2-adrenergic receptor sensitivity assessed in vitro on PBMC. Over a 5-year study, 115 spousal AD caregivers completed annual assessments of caregiving stress, mastery, and PBMC β 2-adrenergic receptor sensitivity, as assessed by in vitro isoproterenol stimulation. Heightened caregiving stress was associated with decreased receptor sensitivity (P = 0.009) whereas greater sense of personal mastery was associated with increased receptor sensitivity (P = 0.038). These results suggest that increased stress may be associated with a desensitization of β 2-receptors, which may contribute to the development of illness among caregivers. However, increased mastery is associated with increased receptor sensitivity, and may therefore serve as a resource factor for improved health in this population.