Long-term follow-up of clinical trial participants: Predictors of post-trial response in older subjects.

BACKGROUND AND OBJECTIVE: The post-trial follow-up (PTFU) phase of a clinical trial can provide important information on maintenance of intervention effects. However, approaches for the PTFU are rarely described. This short communication describes our process for PTFU that involved recontacting older subjects who participated in a clinical trial between 2015 and 2019. We also describe correlates of response to our PTFU survey. METHODS: The parent clinical trial aimed to reduce depression symptoms among older spousally-bereaved adults. We attempted to recontact our sample during the early stages of the COVID-19 pandemic. Using logistic regression, we examined physical health, depression symptoms, cognitive status, and disability as correlates of participant response to the PTFU phase. RESULTS: Forty-two percent of participants responded to the PTFU survey. Disability - or the inability to participate in major life tasks and social roles - was significantly associated with response. Participants with greater disability were less likely to respond to the PTFU survey. CONCLUSIONS: Older adults with disabilities may need alternative and supportive strategies for engaging in the PTFU phase. CLINICAL TRIALS REGISTRATION: NCT02631291.

Risk for Complicated Grief After the COVID-19 Death of a Marital Partner in Late Life.

OBJECTIVE: To identify 1) complicated grief symptom clusters among acutely-bereaved older adults who have lost a spouse to COVID-19 and 2) if spousal death due to COVID-19 increased risk of developing probable PGD METHODS: Eighty adults participating in a randomized controlled trial for depression prevention (mean age [± SD] = 70.4 [6.6]) completed the Inventory of Complicated Grief, every 3 months over a maximum of 15 months. Twenty-four percent (n = 19) of participants lost a spouse to COVID-19; 76% (n = 61) lost a spouse to other causes of death. Adjusted linear regression examined the associations between COVID-19 bereavement and six symptom clusters: yearning and preoccupation, anger and bitterness, shock and disbelief, estrangement from others, hallucinations, and behavior change. RESULTS: Compared to the non-COVID-19 group, the COVID-19 bereaved group reported greater shock and disbelief, hallucinations of the deceased, and estrangement from others. COVID-19 death was also associated with higher risk for probable prolonged grief disorder (PGD) at 12 months (odds ratio = 4.38, p = 0.027). CONCLUSIONS: Older adults who have lost a spouse to COVID-19 present with specific symptoms of distress and may eventually require clinical care for PGD.

Incorporating technology in research with older bereaved adults: Lessons learned from conducting an internet-based randomized controlled trial.

Objective: Digital health interventions (DHI) involve multiple interactions between the user, technology platform, and study team, posing challenges for implementation. This paper describes the lessons learned while implementing an internet-based randomized controlled trial (RCT) for reducing depression symptom burden in older acutely-bereaved adults. Methods: The RCT was entitled "Widowed Elders' Lifestyle after Loss" (or WELL), which compared the efficacy of a DHI to an enhanced usual care (EUC) for reducing depression symptoms in adults 60+ years who lost their spouse/life partner within the previous 12 months. Participants randomized to the DHI used their own tablet, smartphone, or pc to record the timing and regularity of sleep, meals, and physical activity twice daily, for 12 weeks. The also received weekly health coaching sessions from a clinician certified in motivational interviewing. Participants randomized to the EUC arm received weekly calls from research staff and were assessed on the same schedule as intervention participants. All study procedures were conducted virtually. Methodological and procedural challenges were discussed weekly with study staff and the primary investigator. Results: Many challenges can be categorized as follows recruiting virtually, obtaining informed consent, training older adults to use technology, and establishing rapport with older adults. Solutions required researcher and interventionist flexibility in adapting to new strategies. For instance, we redesigned the informed consent process to include a user-friendly brochure that enhanced participants' understanding of the RCT and improved our enrollment rate. We also utilized user-engagement in refining an intervention protocol. Conclusion: We resolved implementation challenges without compromising internal validity via interdisciplinary collaborations with mobile programmers to ensure our technology met the unique and varied needs of aging users. The solutions from this study may promote the recruitment and retainment of older adults in research studies that use technology-based interventions.

Psychosocial interventions to improve adherence in depressed and anxious older adults prescribed antidepressant pharmacotherapy: a scoping review.

Medication nonadherence in depressed and anxious older adults is prevalent and associated with non-response to antidepressant pharmacotherapy. Evidence-based options to improve medication adherence are limited in this population. To review the state of the literature on the types and efficacy of psychosocial interventions for improving antidepressant pharmacotherapy adherence in depressed and anxious older adults. We conducted a scoping review according to PRISMA-ScR guidelines. PubMed/Medline and article references starting in 1980 up to 28 February 2023 were reviewed. Of the 710 records screened, 4 psychosocial interventions were included in the review. All studies included depressed older adults, and none included anxious older adults. Samples included racial and ethnic minorities and were primarily women. The psychosocial interventions consisted mainly of psychoeducation with usual care as the control comparison. Measures of antidepressant adherence included self-reported adherence or pill counting. Three of the four randomized controlled trials improved medication adherence rates and reduced depression symptom burden. Effective interventions exist for improving antidepressant medication adherence in depressed older adults. Improved adherence can reduce depression symptom burden. The lack of interventions for anxious older adults highlights the need to develop and deliver interventions for anxious older adults prescribed antidepressant pharmacotherapy.

Interpersonal Support Domains Associated With Symptoms of Posttraumatic Stress Among Older Black and White Adults.

Objective: Older adults experience numerous changes in their social networks and social environment that may worsen preexisting posttraumatic stress disorder (PTSD) symptoms. This study tested whether tangible support, appraisal support, belonging support, and self-esteem were associated with trauma symptom burden among community-dwelling older Black and White adults at baseline and over 12 months of follow-up.Methods: This study used data collected from a randomized controlled trial for depression prevention in adults 50 years of age or older who had subsyndromal depression (2006-2011). Two hundred forty-four participants (including 90 older Black adults) were randomly assigned to a problem-solving therapy arm or an active control arm. The Interpersonal Support Evaluation List (ISEL) was administered at baseline and 12 months later. Linear regression analysis was used to examine associations of each of the ISEL dimensions with DSM-IV-defined PTSD symptoms at baseline and over time, with control for well-established correlates of PTSD including depression, anxiety, and sleep quality.Results: Participants were a mean (SD) of 65.6 (11.0) years of age, and 71% percent were female. Belongingness support was the only dimension of interpersonal support significantly associated with PTSD symptoms at baseline (ß = -0.192, t = -3.582, P < .001) and 12 months later (ß = -0.183, t = -2.735, P < .01). Regression models accounted for a large proportion of variance in PTSD symptoms. The association between belongingness support and PTSD symptoms did not vary by participant race.Conclusions: A strong perception of belongingness to family and/or friends was associated with fewer PTSD symptoms at baseline and over 12 months. This observation generates the hypothesis that behavioral interventions which directly target and modify interpersonal support may benefit both older Black and older White adults who have experienced trauma.Trial Registration: ClinicalTrials.gov identifier: NCT00326677.

Depressive symptoms anticipate behavioral and emotional factors among older adults: A prospective cross-lagged panel design.

This study examined the temporal relationship among depression, anxiety, insomnia, perceived stress, and physical activity in adults aged 60+ years with a history of major depressive disorder. We conducted a longitudinal study with 12 weeks of follow-up. Assessments consisted of phone or video interviews and included questionnaires evaluating depression, anxiety, insomnia, perceived stress, and physical activity. Our analytic approach consisted of a depression-focused cross-lagged panel model (CLPM) to examine week-to-week correlations among the five measures. The depression-focused CLPM identified statistically significant week-to-week self-predictive effects for each of the five measures. Higher depressive symptom burden was a strong predictor of increased stress, greater insomnia, and less physical activity the following week. No other cross-measure predictions were statistically significant. Our analytical approach clarifies the directional relationship among variables that typically co-occur with depression showing that higher depression symptom burden predisposes older adults to poor sleep, a reduced level of daytime activity, and a greater sense of stress. These findings support the need for longitudinal assessments and targeted interventions for reducing symptoms of depression in older adults.

Rest-Activity Rhythm Characteristics Associated With Depression Symptoms in Stroke Survivors.

OBJECTIVE: To examine which 24-hour rest-activity rhythm (RAR) characteristics are associated with depression symptoms in stroke survivors. DESIGN: Cross-sectional observational study examining associations of RAR characteristics with the presence of depression symptoms adjusting for age, sex, race, and medical comorbidity. SETTING: Community setting. PARTICIPANTS: Stroke survivors: (1) recruited locally (N women=35, N men=28) and (2) a nationally representative probability sample (the National Health and Nutrition Examination Survey [NHANES]; N women=156, N men=124). INTERVENTIONS: None. MEASUREMENTS: Objective RAR characteristics derived from accelerometer recordings including activity onset/offset times and non-parametric measures of RAR strength (relative amplitude), stability (interdaily stability), and fragmentation (intradaily variability). The presence of depression symptoms was categorized using Patient Health Questionnaire scores. RESULTS: In both samples, the only RAR characteristic associated with depression symptoms was intradaily variability (fragmentation): local sample, odds ratio=1.96 [95% confidence interval=1.05-3.63]; NHANES sample, odds ratio=1.34, [95% confidence interval=1.01-1.78]). In the NHANES sample, which included both mild and moderate/severe depression, the association between 24-hour sleep-wake fragmentation and depression symptoms was driven by moderate-to-severe cases. CONCLUSIONS: Stroke survivors with higher levels of RAR fragmentation were more likely to have depression symptoms in both samples. These findings have implications, given prior studies in general samples linking RAR fragmentation with future depression and dementia risk. Research is needed to establish the potential consequences, mechanisms, and modifiability of RAR fragmentation in stroke survivors.

A digital health intervention to stabilize the 24-hour rhythm of sleep, meals, and physical activity for reducing depression among older bereaved spouses: Protocol for a randomized controlled trial.

BACKGROUND: Despite the high prevalence of depression and disruption to 24-h sleep-wake routines following the death of a spouse in late-life, no bereavement interventions have been developed to re-entrain a regular sleep-wake routine among older widow(er)s. We describe the rationale and methodology of the NIH-funded WELL Study (Widowed Elders' Lifestyle after Loss), a randomized controlled trial (RCT) comparing the efficacy of a digital health intervention (DHI) to enhanced usual care (EUC) arm for reducing depression symptoms in older spousally-bereaved adults. METHODS: We will randomize approximately 200 recently bereaved (<12 months) adults aged 60+ years to one of two 12-week interventions: digital monitoring of the timing and regularity of sleep, meals, and physical activity plus weekly motivational health coaching; or enhanced usual care consisting of weekly telephone calls and similar assessment schedules. Participants will complete self-report and clinical assessments at baseline, post-intervention, and 3-, 6-, and 12-months post-intervention, and objective actigraphic assessments of their 24-h rest-activity rhythm (RAR) at baseline and 1-, 2-, and 3-months during the intervention. The primary outcome is change in depression symptoms burden (using the Hamilton Rating Scale for Depression) from pre- to post-intervention and over 12 months of follow-up. DISCUSSION: WELL Study findings will inform the development of widely generalizable and scalable technology-based interventions to support bereaved spouses in community-based settings. Clinical http://Trials.gov Identifier: NCT04016896.

A Multimethod Examination of Medical Students' Experiences With Bereavement and Complicated Grief.

Few studies have examined grief in medical students. This study used a multimethod approach to describe how bereavement and CG may impact medical students' educational experience and their perspectives on grief support and training. One hundred three medical students completed an online survey with quantitative and qualitative methods. Seventy-three (71%) students reported experiencing bereavement, of which 12 (18%) screened positive for CG. Medical students who screened positive for CG reported significantly more emotional and behavioral challenges (M = 3.58 [SD = 2.64]) compared to medical students without CG (M = 0.93 [SD = 1.58], p < .001). Qualitative analyses revealed that bereaved and nonbereaved students wanted more grief education and bereavement support from medical institutions. Therefore, it is crucial for medical institutions, to acknowledge that grief and bereavement may impact students' performance due to multifactorial causes.

Predicting Medication Nonadherence in Older Adults With Difficult-to-Treat Depression in the IRL-GRey Randomized Controlled Trial.

OBJECTIVE: Nonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication nonadherence in difficult-to-treat late-life depression. METHODS: Secondary analysis of data from a clinical trial of antidepressant pharmacotherapy for Major Depressive Disorder in 468 adults aged 60+ years. All participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was assessed 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that may predict antidepressant nonadherence during early (weeks 1-6), late (weeks 7-12), and augmentation (weeks 13--24) treatment. RESULTS: Poor cognitive function and early response were predictive of early nonadherence. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment. CONCLUSION: Future studies should consider the role of early response and cognitive function to improve antidepressant adherence, particularly among older adults who live alone.

Pediatric Sleep Disturbances and Symptoms of Depression in Older Adults.

We investigated the association between retrospectively reported sleep disturbances during childhood and adolescence and current symptoms of depression and anxiety in older adults. Participants included 116 older adults (M age = 68 years [SD = 6.4 years]) who completed a battery of sleep and psychological assessments. We tested two multivariate regression models using age, sex, race, physical illness burden, insomnia status, and pediatric sleep disturbances as correlates of depressive symptoms and anxiety symptoms. Pediatric sleep disturbances were significantly associated with greater depressive symptomatology (ß = 0.247, p = .010), independent of current insomnia status. Medium effect sizes were reported. Our results suggest that pediatric sleep disturbances may be a biobehavioral signal for the development of poor emotional health across the lifespan. Future research should identify critical windows of development when sleep disturbances might be most impactful on emotional health trajectories.

Adaptation and Pilot Study of a Behavioral Intervention Targeting Morning Activation Deficits in Dementia Caregivers: Scheduling Activity and Monitoring Mornings (SAMM).

OBJECTIVES: Morning activation deficits (MADs) correlate with depression symptom persistence in older dementia caregivers. To clarify the potential of MADs as a target for depression interventions, we aimed to: 1) adapt an existing behavioral activation program, Engage therapy, to target mornings; and 2) evaluate effects on self-reported MADs and depression symptoms. METHODS: While trialing the 9-week Engage adaption (targeting mornings) in six older dementia caregivers, we incorporated feedback and finalized an adapted program called Scheduling Activity and Monitoring Mornings (SAMM). We delivered the SAMM protocol to 13 dementia caregivers (all female; mean age = 69, standard deviation = 7). We report modifications made/rationale, as well as changes in subjective MADs (relevant items from the Composite Scale of Morningness) and depression symptoms (Patient Health Questionnaire - 9). RESULTS: Using caregiver and expert input, we adapted the protocol to: include educational materials/content describing the potential relationship between morning inactivity and depression; target activity scheduling within 2 hours of awakening (preferably earlier); and focus only on the main components of morning activity scheduling, planning, and monitoring. This program was associated with decreases in subjective MADs averaging 29% at week 4, 52% at week 6, and 57% by week 9 (all p's <0.005). Initial depression symptoms were significantly reduced, by 62%, at week 9. CONCLUSIONS: These preliminary findings suggest that subjective MADs can be modified pragmatically, and that doing so may have antidepressant effects. A controlled trial with measures of the putative mechanism is needed to clarify whether, and if so how, targeting MAD with SAMM causally perturbs depression's mechanisms.

Multidimensional Sleep Health and Physical Functioning in Older Adults.

Objective: To examine the association between multidimensional sleep health and objective measures of physical functioning in older adults. Method: We conducted a secondary analysis of 158 adults ≥65 years who participated in Midlife in the United States (MIDUS) 2 and MIDUS Refresher studies. Physical functioning was assessed using gait speed during a 50-foot timed walk, lower extremity strength via chair stand test, and grip strength via hand-held dynamometers. Composite multidimensional sleep health scores were derived from 1 week of sleep diaries and wrist actigraphy. Results: Multiple linear regression was used to examine the associations between multidimensional sleep health and physical functioning measures. In adjusted regression analyses, multidimensional sleep health was significantly positively associated with gait speed but not lower extremity strength or grip strength. Discussion: These findings suggest multidimensional sleep health may contribute to physical functioning in older adults. Longitudinal examinations are needed to determine the value of multidimensional sleep health as a therapeutic target to optimize physical functioning.

The Effects of Gait Speed and Psychomotor Speed on Risk for Depression and Anxiety in Older Adults with Medical Comorbidities.

BACKGROUND/OBJECTIVES: Gait speed and psychomotor speed slow with age and may predict neuropsychiatric disease such as depression and anxiety. We explored the relative predictive values of gait speed, psychomotor slowing, and a composite index of these two measures on time to new episode depression or anxiety in older adults at risk for these common psychiatric conditions. DESIGN: Randomized controlled prevention trial with 15-month follow-up. SETTING: University-based late-life mental health research clinic. PARTICIPANTS: Two hundred thirteen individuals, age 60+ years, with subsyndromal symptoms of depression or anxiety and one of the following risk factors for these common conditions: mild cognitive impairment, knee osteoarthritis, or disabilities requiring home-based care. INTERVENTION: Participants in each of the risk factor groups were randomized to a depression-specific preventive intervention or usual care. MEASUREMENTS: Gait speed: 4-m walk test from the Short Physical Performance Battery. Psychomotor speed: Coding task of the Repeatable Battery for the Assessment of Neuropsychological Status. We created a composite index of slowing by determining whether participants exceeded established cut-offs for slow performance in both gait speed (≤0.8 m/s) and psychomotor speed (<7 on the coding task). Time to new onset syndromal depression/anxiety was measured using research diagnostic criteria. RESULTS: Fifty-four participants developed syndromal depression/anxiety (19.5%) over the course of 15 months. Participants with slowing in both areas were over twice as likely to experience new onset depression/anxiety (hazard ratio (HR) = 2.11; 95% confidence interval (CI) = 1.02-4.40, P = .046) compared to participants with no slowing in either area. Slowed gait (HR = 1.88; 95% CI = 0.992-3.55; P = .052) or slowed psychomotor speed (HR = 0.60; 95% CI = 0.14-2.58; P = .488) alone did not increase risk for depression/anxiety. CONCLUSION: Evaluating both gait and psychomotor speed in older adults with medical comorbidities and sub-syndromal depression may predict incident mental illness and inform prevention planning. Future research is needed to validate our observations and explore shared neurobiological mechanisms that explain this elevated risk.

Cross-Cultural Experiences of Hospice and Palliative Care Services: A Thematic Analysis.

Significant disparity exists among non-Western and minority individuals in hospice and palliative care services. A cross-cultural approach that addresses the needs of these patients would decrease this disparity. This study reviews the literature on the experiences of patients from non-Western and minority cultural backgrounds in hospice and palliative care services to inform clinical practice by Western providers. The PubMed database was searched for qualitative studies on patient and family member experiences of end-of-life services among minority or non-Western cultural groups. Eighteen articles met eligibility criteria. The major themes identified include the following: communication and the flow of information, perceptions of hospice and palliative care, and compatibility with cultural beliefs. This review demonstrates similar themes across many non-Western and minority cultures when interacting with hospice and palliative care services. These findings emphasize the importance of a cross-cultural approach in a palliative care and hospice setting.

Timing of Daily Activities over a 24-Hour Period and Affective Status among a National Cohort of Older Dementia Caregivers.

Objective: To examine the allocation of daily activities over a 24-hour period in caregivers (CGs) with and without a probable affective disorder. Methods: Participants were 192 older dementia CGs (mean age = 72.9 years, 70% female) who participated in the National Study of Caregiving. Time diary data were used to measure the duration and timing that caregivers were doing hygienic self-care, eating/drinking, household care, physical caregiving, medical caregiving, socializing, and television viewing. Affective status was assessed using the two-item Patient Health Questionnaire and the Generalized Anxiety Disorder screeners. Results: CGs were more likely to screen positive for depression/anxiety symptoms if they started hygienic self-care later (OR = 1.76, 95% CI = 1.10-2.83) and started medical caregiving later (OR = 2.34, 95% CI = 1.24-4.41). Hygienic self-care start times attenuated the effects of medical caregiving on the affective status. Discussion: Later timing of hygienic self-care may be an important behavioral response that contributes to affective disorder risk in dementia CGs.

Subjective Sleep Quality and Trajectories of Interleukin-6 in Older Adults.

BACKGROUND: We aimed to identify trajectories of inflammation in older adults at elevated risk for syndromal depression and anxiety and to determine whether baseline physical, cognitive, and psychosocial factors could distinguish 15-month longitudinal trajectories. METHODS: Older adults (N = 195, mean age (±SD) = 74.4 years (9.0) participating in three depression and anxiety prevention protocols completed a comprehensive battery of psychosocial assessments and provided blood samples for analysis of interleukin-6 (IL-6) every 3 months over a maximum of 15 months. Group-based trajectory modeling identified trajectories. Adjusted logistic regression examined associations between baseline factors and trajectory groups. RESULTS: Two 15-month trajectories were identified: stable lower IL-6 levels (84%; mean (±SD) = 3.2 (2.1) pg/mL); and consistently higher IL-6 levels (16%; mean = 9.5 (7.4) pg/mL). Poor sleep quality predicted consistently higher levels of IL-6 (OR = 1.9, 95% CI = 1.03-3.55). CONCLUSION: Poor sleep quality may represent a therapeutic target to reduce inflammation.

Resting-State Function Connectivity Associated With Being a "Morning-Type" Dementia Caregiver and Having Lower Depression Symptom Severity.

OBJECTIVES: A lack of "morningness" predicts greater depression symptom severity over time, including in a vulnerable group of older adults: family dementia caregivers (dCGs). Evidence regarding the neurobiological basis of these correlations is needed to guide future research towards biomarker-informed detection and prevention approaches. We therefore primarily aimed to identify simple resting-state biomarkers that correlated with a lack of "morningness" in dCGs. METHOD: We examined 54 dCGs (mean age = 70, range: 61-84; 70% female) of whom 40% were definite "morning types" according to Composite Scale of Morningness (CSM). Using a 7 Tesla resting-state sequence, we compared the functional connectivity of nodes in networks previously implicated in depression (fronto-parietal, default mode, limbic, and salience) between caregivers who were and were not "morning types." RESULTS: Correcting for voxel-wise comparisons, "morning-type" dCGs had less amygdala-posterior cingulate connectivity (Cohen's d = -1.3), which statistically mediated ~32% of the association between the degree of "morningness" and lower depression severity. Post hoc analyses of CSM items found significant correlations, with both amygdala-posterior cingulate FC and depression severity, for 4/6 items pertaining to difficulty, 2/5 items pertaining to preference, and 0/2 items pertaining to typical patterns. DISCUSSION: Prior research shows that amygdala-posterior cingulate connectivity increases when allocating attention to peripheral aspects of negative emotional stimuli. As such, difficulty with morning activation may relate to the ongoing direction of focus around distressing content; in contrast, morning activity participation may serve to limit focus on distress. Replication and experimental studies are required to confirm these associations and their modifiability.