Cathy Alessi’s research while affiliated with University of California, Los Angeles and other places

This paper describes the methodology and outcomes of development of a trauma-informed protocol for cognitive behavioral therapy for insomnia (CBT-I). Methods included 1) convening an expert panel of U.S. Department of Veterans Affairs providers (n = 4) to identify trauma-related symptoms that may interfere with standard CBT-I delivery and to assess trauma-informed adaptations to an existing CBT-I protocol; 2) presenting adapted protocol materials to veteran engagement groups for feedback; 3) sequentially delivering the trauma-informed CBT-I protocol to women veterans (n = 5) with iterative refinement of the intervention materials and evaluation of clinical improvement (Insomnia Severity Index and Pittsburgh Sleep Quality Index total scores and sleep diaries). Trauma-informed adaptations to CBT-I included PTSD diagnosis psychoeducation, nighttime hyperarousal reduction strategies, nightmare/sleep avoidance psychoeducation, behavior tracking to challenge avoidance, psychoeducation about trauma-related thoughts, and orientation to PTSD treatments. Veteran engagement group consensus supported expert feedback. Women who completed trauma-informed CBT-I reported improved sleep outcomes from baseline to 3-month follow-up and high perceived acceptability and clarity regarding trauma-informed adaptations. This efficient, multi-step approach resulted in an acceptable, efficacious protocol for use in a randomized clinical trial. These methods can be applied to other protocols to systematically adapt other psychotherapies for patients with PTSD.

Cognitive-behavioral therapy for insomnia (CBT-I) improves comorbid mental health symptoms (depression, anxiety, and posttraumatic stress disorder [PTSD]), with sleep improvements hypothesized as the mechanism for the observed improvements. This study examined change in insomnia severity as a mediator of mental health symptom improvements in women veterans following behavioral insomnia treatment. Secondary analysis was conducted using data from a comparative effectiveness trial that evaluated insomnia outcomes in women veterans following CBT-I and an acceptance and commitment therapy-informed insomnia (ABC-I) treatment. The treatments were statistically equivalent in improving sleep, so were combined for the current analyses. The sample included 149 middle-age women veterans of diverse race and ethnicity (mean age 48 years, 34.2% White, 26.9% Black or African American, 18.8% Hispanic/Latinx). Variables of interest included insomnia severity (Insomnia Severity Index), and measures of depression (Patient Health Questionnaire–9) and generalized anxiety (Generalized Anxiety Disorder–7). A generalized structural equations model was conducted to test study hypotheses. Study treatment phase (baseline, posttreatment, 3-month follow-up) significantly predicted depression (–3.95 ≤ b ≤ –4.35, p < .001) and anxiety (–4.29 ≤ b ≤ –4.75, p < .001) symptom improvement in nonmediation models. Insomnia severity mediated improvement in depression and anxiety symptoms (0.515 ≤ b ≤ 0.584, p < .001), with change in insomnia severity accounting for 88%–97% of depression and anxiety symptom reduction following insomnia-focused behavioral psychotherapies. This study identified reduction in insomnia severity as a major mechanism of improvement in depression and anxiety symptoms following behavioral insomnia treatment. Findings also reinforce the value of insomnia-focused behavioral psychotherapies in patients with comorbid mental health conditions.

Family caregivers of people living with dementia (PLWD) have an increased risk of dementia. Poor sleep is common among caregivers, but the relationship between sleep and biomarkers of neurodegeneration in this population is unknown. In a secondary analysis of data from a behavioral sleep intervention trial among caregivers of PLWD, we tested the relationship between subjective and objective sleep and plasma biomarkers of neurodegeneration and explored the preliminary effects of the intervention on these biomarkers. Participants included 18 caregivers of PLWD who received a sleep education program (active treatment versus control). Sleep measures included the Pittsburgh Sleep Quality Index, total nights of good sleep (sleep diary), and wrist- actigraphy-measured sleep duration, sleep efficiency (SE), and total wake time (TWT). Plasma biomarkers included amyloid beta-40 (Aβ40), amyloid beta-42 (Aβ42), Glial Fibrillary Acidic Protein (GFAP), Neurofilament light (NfL), and Aβ42/40 ratio. All measures were collected at baseline (n=18), post-intervention (n=11), and three months (n=7). Pearson correlations and t-tests were performed. At baseline, greater (worse) TWT was associated with higher Aβ40 (r=0.60, p=0.009) and Aβ42 (r=0.62, p=0.006) levels. Lower (worse) SE was associated with higher Aβ40 (r= -0.52, p=0.026), Aβ42 (r= -0.61, p=0.008), and NfL (r= -0.48, p=0.043). Less nights of good sleep were associated with a lower Aβ42/40 ratio (r=0.51, p=0.032). Biomarker levels were not significantly different between treatment and control at follow-ups. In conclusion, poor sleep is associated with increased biomarkers of neurodegeneration among caregivers of PLWD. Larger studies are needed to test whether sleep interventions reduce this population’s neurodegeneration risk.

Background Nocturia (waking from sleep at night to void) and chronic insomnia frequently co‐exist in older adults, contributing synergistically to sleep disturbance. Treatments typically target either nocturia or insomnia rather than simultaneously addressing shared mechanisms for these disorders. Methods We conducted a multisite feasibility study to: (1) test and refine a protocol for recruitment, randomization, and assessment of older adults with co‐existing nocturia and insomnia; and (2) examine preliminary changes in outcome measures to inform a future larger, multisite clinical trial. Participants were men and women aged 60 years and older recruited from outpatient clinics, reporting an average of two or more nocturia episodes per night over the past 4 weeks and meeting diagnostic criteria for chronic insomnia disorder. Participants were randomized to receive either integrated cognitive‐behavioral therapy for insomnia and nocturia or a health education control program involving five weekly visits with a trained nurse practitioner interventionist. Outcomes (e.g., nocturia episodes) were measured 1‐week post‐treatment and 4‐month post‐randomization. Descriptive statistics examined the feasibility of outcomes to guide preparations for a future efficacy trial. Results Of 245 adults screened, 55% were ineligible and 25% declined to participate. Sixty‐one percent of 49 participants who provided informed consent were randomized. Of the 30 participants randomized (mean age = 70.6 years, 60% White), 14 were assigned to integrated cognitive‐behavioral treatment and 16 to the control group. All randomized participants provided 4‐month follow‐up data. At 4 months, mean nightly nocturia episodes decreased by 0.9 (SD 1.0) in the integrated treatment group and by 0.2 (SD 1.2) in the control group compared with baseline. Discussion Findings demonstrate the feasibility of recruiting, randomizing, and collecting outcome data from older adults (predominantly male) assigned to an integrated cognitive‐behavioral therapy for coexisting insomnia and nocturia or a health education control program.

Importance Placebo effects are commonly observed in benzodiazepine receptor agonist hypnotic clinical trials. Clinical guidelines recommend discontinuing benzodiazepine receptor agonist hypnotics (particularly in older adults) and administering cognitive behavioral therapy for insomnia (CBTI) as first-line therapy for insomnia. It is unknown whether a novel intervention that masks the daily dose of benzodiazepine receptor agonist during tapering and augments CBTI with novel cognitive and behavioral exercises targeting placebo effect mechanisms improves benzodiazepine receptor agonist discontinuation. Objective To compare a masked benzodiazepine receptor agonist taper plus augmented CBTI vs an unmasked taper plus standard CBTI. Design, Setting, and Participants This randomized clinical trial conducted at an academic medical center and a Department of Veterans Affairs medical center included adults aged 55 years or older who had used lorazepam, alprazolam, clonazepam, temazepam, and/or zolpidem for current or prior insomnia, at doses of less than 8-mg diazepam–equivalent 2 or more nights per week for at least 3 months. Data were collected between December 2018 and November 2023. Data analyses were conducted between November 2023 and July 2024. Interventions Masked taper plus cognitive behavioral therapy-augmented program (MTcap); standard CBTI plus supervised (unmasked) gradual taper (SGT). Main Outcomes and Measures The primary efficacy outcome was percentage achieving benzodiazepine receptor agonist discontinuation 6 months after treatment ended (6-month; intention-to-treat) measured with 7-day self-reported medication logs and for a subset, urine tests. Secondary outcomes were Insomnia Severity Index scores at 1 week posttreatment and 6 months posttreatment, percentage of participants that have discontinued benzodiazepine receptor agonist use at 1 week posttreatment, and benzodiazepine receptor agonist dose and the Dysfunctional Beliefs About Sleep-Medication subscale at 1 week and 6 months posttreatment. Results Of 338 participants who underwent in-depth screening, 188 participants (mean [SD] age, 69.8 [8.3] years, 123 male [65.4%] and 65 female [35.6%]) were randomly assigned to MTcap (n = 92) or SGT (n = 96). Compared with SGT, MTcap resulted in greater benzodiazepine receptor agonist discontinuation at 6 months (MTcap = 64 [73.4%], SGT = 52 [58.6%]; odds ratio [OR], 1.95; 95% CI 1.03-3.70; P = .04) and 1 week posttreatment (MTcap = 76 [88.4%], SGT = 62 [67.4%]; OR, 3.68; 95% CI, 1.67-8.12; P = .001) and reduced frequency of benzodiazepine receptor agonist use (nights/week) at 1 week posttreatment (−1.31; 95% CI, −2.05 to −0.57; P < .001). Insomnia Severity Index improved with no significant between-group difference at follow-up (baseline to 1 week posttreatment, 1.38; P = .16; baseline to 6 months, 0.16; P = .88). Conclusions and Relevance This randomized clinical trial found that a program combining masked tapering with novel cognitive and behavioral exercises targeting placebo mechanisms improved the percentage of long-term benzodiazepine receptor agonist discontinuation compared with standard CBTI plus an unmasked taper. Trial Registration ClinicalTrials.gov Identifier: NCT03687086

Insomnia and obstructive sleep apnea are the two most prevalent sleep disorders and frequently co-exist. People with co-morbid insomnia and sleep apnea (COMISA) experience worse sleep, daytime function, mental health, physical health and quality of life, compared to people with neither disorder, and often compared to people with insomnia alone or sleep apnea alone. Despite the high prevalence and substantial morbidity associated with COMISA, few studies have investigated specific treatment approaches for this patient population. People with COMISA have unique assessment, diagnosis and management requirements, and may be more complex to effectively treat compared to people with either disorder presenting alone. It is important to avoid routinely viewing insomnia as a ‘secondary symptom’ of OSA when they co-occur. This chapter presents an overview of the prevalence, consequences, and treatment approaches for COMISA, and recommend methods to improve the management of COMISA in sleep clinic settings. We advocate for a model of care that allocates specific diagnostic and treatment attention to each condition when they co-occur, which is likely to result in the greatest therapeutic outcomes for COMISA.

Since their inception in 1975, the Department of Veterans Affairs Geriatric Research, Education, and Clinical Centers (GRECCs) have served as incubators of innovation in geriatrics. Their contributions to the VA mission were last reviewed in 2012. Herein, we describe the continuing impact of GRECCs in research, clinical, and educational areas, focusing on the period between 2018 and 2022. GRECC research spans the continuum from bench to bedside, with a growing research portfolio notable for highly influential publications. GRECC education connects healthcare professions trainees and practicing clinicians, as well as Veterans and their caregivers, to engaging learning experiences. Clinical advancements, including age‐friendly care, span the continuum of care and leverage technology to link disparate geographical sites. GRECCs are uniquely positioned to serve older adults given their alignment with the largest integrated health system in the United States and their integration with academic health centers. As such, the GRECCs honor Veterans as they age by building VA capacity to care for the increasing number of aging Veterans seeking care from VA. GRECC advancements also benefit non‐VA healthcare systems, their academic affiliates, and non‐Veteran older adults. GRECCs make invaluable contributions to advancing geriatric and gerontological science, training healthcare professionals, and developing innovative models of geriatric care.

Objective Poor sleep is associated with increased inflammation, thereby increasing the risk of chronic diseases and mortality. However, the effects of behavioral sleep interventions on the upstream inflammatory system are unknown among family care partners (CP). The present study explored the role of a behavioral sleep intervention program on inflammatory gene expression. Methods This was part of a randomized controlled trial of a sleep intervention for dementia care dyads with sleep problems. Thirty dyads were randomized to sleep intervention or control groups. Sleep outcomes for CP were assessed with 1 week of actigraphy and sleep diary, and the Pittsburgh Sleep Quality Index. Other information included CP demographics, body mass index, and intensity of caregiving tasks. All outcomes were collected at baseline, post-treatment, and 3-month follow-up. Results Neither group showed any significant differential changes in gene expression from baseline to post-treatment or 3-month follow-up. A decrease in inflammatory gene expression was significantly associated with more nights of good sleep (i.e. nights without trouble falling or staying asleep at night). This finding remained significant after controlling for group (intervention/control), timepoint (baseline, post-treatment, and 3-month follow-up), and CP characteristics (e.g. age and ethnicity). Conclusions Although better sleep was associated with decreased inflammatory gene expression, this study did not demonstrate any benefits of a behavioral sleep intervention over control, most likely due to a small sample. Studies with larger sample sizes are needed to test the specific aspects of disturbed sleep that relate to inflammatory biology among CP of persons living with dementia.

Background Cognitive behavioral therapy for insomnia (CBT‐I) is the gold‐standard treatment for insomnia disorder in adults. Compared to young adults, older adults have increased risk for the development of conditions associated with chronic pain, which may impact the efficacy of CBT‐I in improving insomnia symptoms in older adults. This study evaluated the effect of participant‐rated pain on sleep‐related outcomes of a supervised, non‐clinician administered CBT‐I program in older adult patients with chronic insomnia disorder. Methods Secondary analysis was conducted using data from a randomized controlled trial among 106 community‐dwelling older adult veterans ( N = 106; mean age 72.1 years, 96% male, 78.3% White, 6.6% Hispanic, 5.7% African American) with chronic (≥3 months) insomnia disorder. Participants engaged in five sessions of manual‐based CBT‐I in individual or group format within one Department of Veterans Affairs healthcare system, provided by non‐clinician “sleep coaches” who had weekly telephone supervision by behavioral sleep medicine specialists. Insomnia symptoms (Insomnia Severity Index), perceived sleep quality (Pittsburgh Sleep Quality Index), fatigue (Flinder's Fatigue Scale), daytime sleepiness (Epworth Sleepiness Scale), and perceived pain severity (items from the Geriatric Pain Measure) were assessed at 4 time points: baseline, one‐week posttreatment, 6‐month follow‐up, and 12‐month follow‐up. Mixed effects models with time invariant and time varying predictors were employed for analyses. Results CBT‐I improved insomnia symptoms, perceived sleep quality, fatigue, and daytime sleepiness among older veterans with chronic insomnia. Participant‐reported pain was associated with greater improvements in insomnia symptoms following CBT‐I. Pain did not affect improvements in other sleep‐related outcomes (−0.38 ≤ b ≤ 0.07, p > 0.05). Between‐subjects differences in pain, but not within‐subject changes in pain over time, appeared to play a central role in insomnia symptom improvement at posttreatment, with individuals with higher‐than‐average pain showing greater insomnia symptom improvement (ISI score reduction; −0.32 ≤ b ≤ −0.28, p ≤ 0.005). Conclusions Pain did not meaningfully hinder the effects of CBT‐I on sleep outcomes. Among older veterans with chronic insomnia disorder, individuals with higher pain exhibited slightly greater improvement in insomnia than those with lower levels of pain. These findings suggest that experiencing pain does not impair treatment response and should not preclude older adults with insomnia from being offered CBT‐I.