Sex differences in plasma proteomic markers in late-life depression.

Previous studies have shown significant sex-specific differences in major depressive disorder (MDD) in multiple biological parameters. Most studies focused on young and middle-aged adults, and there is a paucity of information about sex-specific biological differences in older adults with depression (aka, late-life depression (LLD)). To address this gap, this study aimed to evaluate sex-specific biological abnormalities in a large group of individuals with LLD using an untargeted proteomic analysis. We quantified 344 plasma proteins using a multiplex assay in 430 individuals with LLD and 140 healthy comparisons (HC) (age range between 60 and 85 years old for both groups). Sixty-six signaling proteins were differentially expressed in LLD (both sexes). Thirty-three proteins were uniquely associated with LLD in females, while six proteins were uniquely associated with LLD in males. The main biological processes affected by these proteins in females were related to immunoinflammatory control. In contrast, despite the smaller number of associated proteins, males showed dysregulations in a broader range of biological pathways, including immune regulation pathways, cell cycle control, and metabolic control. Sex has a significant impact on biomarker changes in LLD. Despite some overlap in differentially expressed biomarkers, males and females show different patterns of biomarkers changes, and males with LLD exhibit abnormalities in a larger set of biological processes compared to females. Our findings can provide novel targets for sex-specific interventions in LLD.

Fatness but Not Fitness Linked to BrainAge: Longitudinal Changes in Brain Aging during an Exercise Intervention.

PURPOSE: Fitness, physical activity, body composition, and sleep have all been proposed to explain differences in brain health. We hypothesized that an exercise intervention would result in improved fitness and body composition and would be associated with improved structural brain health. METHODS: In a randomized controlled trial, we studied 485 older adults who engaged in an exercise intervention ( n = 225) or a nonexercise comparison condition ( n = 260). Using magnetic resonance imaging, we estimated the physiological age of the brain (BrainAge) and derived a predicted age difference compared with chronological age (brain-predicted age difference (BrainPAD)). Aerobic capacity, physical activity, sleep, and body composition were assessed and their impact on BrainPAD explored. RESULTS: There were no significant differences between experimental groups for any variable at any time point. The intervention group gained fitness, improved body composition, and increased total sleep time but did not have significant changes in BrainPAD. Analyses of changes in BrainPAD independent of group assignment indicated significant associations with changes in body fat percentage ( r (479) = 0.154, P = 0.001), and visceral adipose tissue (VAT) ( r (478) = 0.141, P = 0.002), but not fitness ( r (406) = -0.075, P = 0.129), sleep ( r (467) range, -0.017 to 0.063; P range, 0.171 to 0.710), or physical activity ( r (471) = -0.035, P = 0.444). With linear regression, changes in body fat percentage and VAT significantly predicted changes in BrainPAD ( ß = 0.948, P = 0.003) with 1-kg change in VAT predicting 0.948 yr of change in BrainPAD. CONCLUSIONS: In cognitively normal older adults, exercise did not appear to impact BrainPAD, although it was effective in improving fitness and body composition. Changes in body composition, but not fitness, physical activity, or sleep impacted BrainPAD. These findings suggest that focus on weight control, particularly reduction of central obesity, could be an interventional target to promote healthier brains.

Relationship between baseline plasma p-tau181 and longitudinal changes in cognition and structural brain measures in a cohort of cognitively unimpaired older adults.

INTRODUCTION: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy. METHODS: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume. RESULTS: In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in cognition and structural brain measures. Also, baseline plasma p-tau levels did not influence the effects of behavioral interventions (exercise or mindfulness) on cognitive and structural brain changes. DISCUSSION: The short follow-up and healthy status of this CU cohort might have limited the sensitivity of plasma p-tau181 in detecting changes associated with AD pathology.

Data-efficient resting-state functional magnetic resonance imaging brain mapping with deep learning.

OBJECTIVE: Resting-state functional MRI (RS-fMRI) enables the mapping of function within the brain and is emerging as an efficient tool for the presurgical evaluation of eloquent cortex. Models capable of reliable and precise mapping of resting-state networks (RSNs) with a reduced scanning time would lead to improved patient comfort while reducing the cost per scan. The aims of the present study were to develop a deep 3D convolutional neural network (3DCNN) capable of voxel-wise mapping of language (LAN) and motor (MOT) RSNs with minimal quantities of RS-fMRI data. METHODS: Imaging data were gathered from multiple ongoing studies at Washington University School of Medicine and other thoroughly characterized, publicly available data sets. All study participants (n = 2252 healthy adults) were cognitively screened and completed structural neuroimaging and RS-fMRI. Random permutations of RS-fMRI regions of interest were used to train a 3DCNN. After training, model inferences were compared using varying amounts of RS-fMRI data from the control data set as well as 5 patients with glioblastoma multiforme. RESULTS: The trained model achieved 96% out-of-sample validation accuracy on data encompassing a large age range collected on multiple scanner types and varying sequence parameters. Testing on out-of-sample control data showed 97.9% similarity between results generated using either 50 or 200 RS-fMRI time points, corresponding to approximately 2.5 and 10 minutes, respectively (96.9% LAN, 96.3% MOT true-positive rate). In evaluating data from patients with brain tumors, the 3DCNN was able to accurately map LAN and MOT networks despite structural and functional alterations. CONCLUSIONS: Functional maps produced by the 3DCNN can inform surgical planning in patients with brain tumors in a time-efficient manner. The authors present a highly efficient method for presurgical functional mapping and thus improved functional preservation in patients with brain tumors.

Associations of Lean Mass, Muscular Strength, and Physical Function with Trabecular Bone Score in Older Adults.

INTRODUCTION/BACKGROUND: Trabecular bone score (TBS) is an indirect measurement of bone quality and microarchitecture determined from dual-energy X-ray absorptiometry (DXA) imaging of the lumbar spine. TBS predicts fracture risk independent of bone mass/density, suggesting this assessment of bone quality adds value to the understanding of patients' bone health. While lean mass and muscular strength have been associated with higher bone density and lower fracture risk among older adults, the literature is limited regarding the relationship of lean mass and strength with TBS. The purpose of this study was to determine associations of DXA-determined total body and trunk lean mass, maximal muscular strength, and gait speed as a measure of physical function, with TBS in 141 older adults (65-84 yr, 72.5 +/- 5.1 yr, 74% women). METHODOLOGY: Assessments included lumbar spine (L1-L4) bone density and total body and trunk lean mass by DXA, lower body (leg press) and upper body (seated row) strength by one repetition maximum tests, hand grip strength, and usual gait speed. TBS was derived from the lumbar spine DXA scan. Multivariable linear regression determined the contribution of proposed predictors to TBS. RESULTS: After adjusting for age, sex, and lumbar spine bone density, upper body strength significantly predicted TBS (unadjusted/adjusted R2= 0.16/ 0.11, ß coefficient =0.378, p=0.005), while total body lean mass index showed a trend in the expected direction (ß coefficient =0.243, p=0.053). Gait speed and grip strength were not associated with TBS (p>0.05). CONCLUSION: Maximum strength of primarily back muscles measured as the seated row appears important to bone quality as measured by TBS, independent of bone density. Additional research on exercise training targeting back strength is needed to determine its clinical utility in preventing vertebral fractures among older adults.

Beyond maintaining safety: Examining the benefit of emotion-centered problem solving therapy added to safety planning for reducing late life suicide risk.

Few clinical trials have examined brief non-pharmacological treatments for reducing suicide risk in older Veterans, a high-risk group. Problem Solving Therapy (PST) is a promising psychosocial intervention for reducing late life suicide risk by increasing adaptive coping to problems through effective problem solving and related coping skills. The current randomized clinical trial will compare the efficacy of six telephone-delivered sessions of Safety Planning (enhanced usual care; EUC) only or an updated version of PST (emotion-centered PST [EC-PST]) + EUC to determine the added clinical benefit of EC-PST for reducing severity of suicidal ideation and for increasing reasons for living, a critical protective factor. Participants randomized to EC-PST + EUC or EUC only will be 150 Veterans (75 each) with active suicidal ideation who are aged 60 or older; have a current DSM-5 anxiety, depressive, and/or trauma-related disorder; and without significant cognitive impairment. Primary outcomes (Geriatric Suicide Ideation Scale and Reasons for Living-Older Adults scale) will be assessed at 11 timepoints: baseline, after each of 6 treatment sessions, posttreatment, and at follow-up at 1, 3, and 6 months posttreatment, and analyzed using mixed effects modeling. Additionally, moderators and mediators of primary outcomes will be examined-functional disability, executive dysfunction, and problem-solving ability. Qualitative feedback from participants will identify potential Veteran-centric changes to the EC-PST protocol and to EUC. Ultimately, the goal of this study is to inform the evidence-based clinical practice guidelines for treatments to reduce suicide risk in older Veterans and specifically to inform clinical decision-making regarding the merit of adding EC-PST to EUC.

Home-based primary care-mental health integration in the Veterans Health Administration: An updated evaluation of practice patterns.

Starting in 2008, the U.S. Veterans Health Administration required the integration of mental health providers (MH providers) in Home-Based Primary Care (HBPC) programs to promote access to and quality of mental health services for veterans enrolled in HBPC. Surveys were administered in both 2010 and 2019 to HBPC program directors and MH providers to evaluate the status of mental health practice in HBPC programs and inform the continued development of program resources. Findings reported here summarize responses to the 2019 survey and highlight changes compared to 2010 in key areas (e.g., mental health staffing and workload, services provided, training needs, and integration with and impact on the HBPC team). In 2019, approximately half of invited HBPC program directors (n = 66) and MH providers (n = 136) completed the voluntary, anonymous, and confidential surveys. Descriptive and bivariate analyses of quantitative data, and thematic analyses of open-text responses, were conducted. Comparisons of survey responses were made between the 2019 surveys and those collected in 2010 from MH providers (n = 132) and program directors (n = 112), and indicated similar patterns of variability in program staffing and practices across sites, with ongoing behavioral/mental health education and training needs reported for both MH providers and teams. The perceived degree and value of mental health integration in HBPC also remained high. Survey responses suggest integration of mental health services into HBPC continues to be feasible and improves access to key services. Findings may inform the expansion of home-based mental health services for meeting the needs of an aging population. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effects of Mindfulness Training and Exercise on Cognitive Function in Older Adults: A Randomized Clinical Trial.

Importance: Episodic memory and executive function are essential aspects of cognitive functioning that decline with aging. This decline may be ameliorable with lifestyle interventions. Objective: To determine whether mindfulness-based stress reduction (MBSR), exercise, or a combination of both improve cognitive function in older adults. Design, Setting, and Participants: This 2 × 2 factorial randomized clinical trial was conducted at 2 US sites (Washington University in St Louis and University of California, San Diego). A total of 585 older adults (aged 65-84 y) with subjective cognitive concerns, but not dementia, were randomized (enrollment from November 19, 2015, to January 23, 2019; final follow-up on March 16, 2020). Interventions: Participants were randomized to undergo the following interventions: MBSR with a target of 60 minutes daily of meditation (n = 150); exercise with aerobic, strength, and functional components with a target of at least 300 minutes weekly (n = 138); combined MBSR and exercise (n = 144); or a health education control group (n = 153). Interventions lasted 18 months and consisted of group-based classes and home practice. Main Outcomes and Measures: The 2 primary outcomes were composites of episodic memory and executive function (standardized to a mean [SD] of 0 [1]; higher composite scores indicate better cognitive performance) from neuropsychological testing; the primary end point was 6 months and the secondary end point was 18 months. There were 5 reported secondary outcomes: hippocampal volume and dorsolateral prefrontal cortex thickness and surface area from structural magnetic resonance imaging and functional cognitive capacity and self-reported cognitive concerns. Results: Among 585 randomized participants (mean age, 71.5 years; 424 [72.5%] women), 568 (97.1%) completed 6 months in the trial and 475 (81.2%) completed 18 months. At 6 months, there was no significant effect of mindfulness training or exercise on episodic memory (MBSR vs no MBSR: 0.44 vs 0.48; mean difference, -0.04 points [95% CI, -0.15 to 0.07]; P = .50; exercise vs no exercise: 0.49 vs 0.42; difference, 0.07 [95% CI, -0.04 to 0.17]; P = .23) or executive function (MBSR vs no MBSR: 0.39 vs 0.31; mean difference, 0.08 points [95% CI, -0.02 to 0.19]; P = .12; exercise vs no exercise: 0.39 vs 0.32; difference, 0.07 [95% CI, -0.03 to 0.18]; P = .17) and there were no intervention effects at the secondary end point of 18 months. There was no significant interaction between mindfulness training and exercise (P = .93 for memory and P = .29 for executive function) at 6 months. Of the 5 prespecified secondary outcomes, none showed a significant improvement with either intervention compared with those not receiving the intervention. Conclusions and Relevance: Among older adults with subjective cognitive concerns, mindfulness training, exercise, or both did not result in significant differences in improvement in episodic memory or executive function at 6 months. The findings do not support the use of these interventions for improving cognition in older adults with subjective cognitive concerns. Trial Registration: ClinicalTrials.gov Identifier: NCT02665481.

Covariance and Correlation Analysis of Resting State Functional Magnetic Resonance Imaging Data Acquired in a Clinical Trial of Mindfulness-Based Stress Reduction and Exercise in Older Individuals.

We describe and apply novel methodology for whole-brain analysis of resting state fMRI functional connectivity data, combining conventional multi-channel Pearson correlation with covariance analysis. Unlike correlation, covariance analysis preserves signal amplitude information, which feature of fMRI time series may carry physiological significance. Additionally, we demonstrate that dimensionality reduction of the fMRI data offers several computational advantages including projection onto a space of manageable dimension, enabling linear operations on functional connectivity measures and exclusion of variance unrelated to resting state network structure. We show that group-averaged, dimensionality reduced, covariance and correlation matrices are related, to reasonable approximation, by a single scalar factor. We apply this methodology to the analysis of a large, resting state fMRI data set acquired in a prospective, controlled study of mindfulness training and exercise in older, sedentary participants at risk for developing cognitive decline. Results show marginally significant effects of both mindfulness training and exercise in both covariance and correlation measures of functional connectivity.

Problem Solving Training for Veterans with Complex Comorbidities: Treatment Delivery Adaptations during COVID-19.

OBJECTIVES: To summarize adaptations due to COVID-19 for VA Problem Solving Training (PST) for clinicians serving medically complex patients and to compare patient mental health outcomes in the year before (2019) and during COVID-19 (2020). METHODS: Clinicians attended a multi-day workshop and up to 6 months of small-group consultation for two training cases. In 2019 and 2020, 122 Veteran patients completed baseline and posttreatment measures of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7 item), and negative problem-solving beliefs (Negative Problem Orientation Questionnaire). Qualitative data were collected on clinician's pandemic-related treatment implementation challenges. RESULTS: Program adaptations during COVID-19 addressed challenges due to delivering treatment by telephone, video, or in person; Veteran patient recruitment barriers; and privacy issues for telephone and video. Veterans in both pre-pandemic and COVID-19 cohorts had significant improvements in depression, anxiety, and negative problem-solving beliefs, with no significant differences in the amount of improvement between the two cohorts. CONCLUSIONS: Flexibilities afforded to clinicians delivering the PST training program during the pandemic addressed key obstacles and barriers to recruitment, and implementation did not diminish the effectiveness of the intervention. CLINICAL IMPLICATIONS: Findings support continued implementation of the PST training program with added flexibility to treatment delivery beyond the pandemic.

Evidence-based assessment of treatment outcomes for late-life generalized anxiety disorder using the Penn State Worry Questionnaire (PSWQ) and Penn State Worry Questionnaire - Abbreviated (PSWQ-A).

OBJECTIVE: The Penn State Worry Questionnaire (PSWQ) is a commonly used measure of treatment outcome for late-life generalized anxiety disorder (GAD). However, there is considerable variability in the definitions used to define treatment response and remission. This study aimed to provide empirically derived guidelines for assessing treatment response and remission among older adults with GAD using the PSWQ and the abbreviated PSWQ (PSWQ-A). DESIGN: Longitudinal assessment of GAD symptoms pre- and posttreatment. PARTICIPANTS: Participants were 259 older adults aged 60-86 years with a diagnosis of GAD who were assessed before and after treatment. INTERVENTION: Participants were randomly assigned to cognitive behavioral therapy or control (waitlist, discussion group, or supportive therapy) conditions. MEASUREMENTS: Signal-detection analyses using receiver operating characteristic (ROC) methods were used to determine optimal agreement between structured diagnostic interviews and scores on the PSWQ and PSWQ-A. RESULTS: Results suggest that a score of ≤51 was optimal for defining diagnostic remission status on the PSWQ, and a score of ≤24 was optimal on the PSWQ-A. A 9% reduction or ≥4-point reduction was optimal for assessing treatment response on the PSWQ. The PSWQ-A was poor at identifying treatment response status. CONCLUSIONS: Findings suggest that most of the previously used definitions have underestimated the treatment effects for late-life GAD. However overall, the PSWQ and PSWQ-A are suboptimal for assessing treatment outcome for late-life GAD. The standardization of response and remission criteria has implications for comparison between treatment trials, and for the benchmarking of outcomes in clinical practice.

Problem-solving training for Veterans in home based primary care: an evaluation of intervention effectiveness.

BACKGROUND: Veterans enrolled in Veterans Health Administration (VHA) Home Based Primary Care (HBPC), a program providing in-home medical and mental health care by an interdisciplinary care team, often face substantial physical, cognitive, and mental health challenges. This program evaluation examined the impact of a brief problem-solving intervention on depressive symptoms, quality of life, and problem-solving abilities for Veterans enrolled in HBPC. DESIGN: Pre- and post-intervention outcomes for Veterans, and qualitative feedback from Veterans and clinicians regarding program satisfaction. PARTICIPANTS AND SETTING: A total of 230 HBPC patients (mean age in years = 72.1, SD = 11.6) within the U.S. national VHA health care system. INTERVENTION: Six-session, individual Problem-Solving Training (PST-HBPC). METHOD: Licensed psychologists and social workers (n = 115) completed training and administered the treatment with HBPC Veterans between 2014 and 2017. MEASUREMENTS AND RESULTS: From baseline to post-intervention, Veterans completing five or more PST-HBPC sessions (n = 199) reported significant reductions in depressive symptoms on the Patient Health Questionnaire 9-item (PHQ-9), in difficulty functioning due to depressive symptoms (PHQ-9 item 10), and in thoughts of death (PHQ-9 item 9). They also reported more effective problem-solving on the Social Problem-Solving Inventory - Revised: Short form (total score and subscales), and improved quality of life across life domains on the World Health Organization Quality of Life-BREF (WHOQOL-BREF) scale. Both clinicians and Veterans also reported satisfaction with the program. CONCLUSIONS: Preliminary findings support the continued dissemination and implementation of this brief PST intervention for HBPC Veterans, and its potential for use with non-VA home care populations with complex comorbidities.

Fatness, fitness and the aging brain: A cross sectional study of the associations between a physiological estimate of brain age and physical fitness, activity, sleep, and body composition.

Introduction: Changes in brain structure and function occur with aging. However, there is substantial heterogeneity both in terms of when these changes begin, and the rate at which they progress. Understanding the mechanisms and/or behaviors underlying this heterogeneity may allow us to act to target and slow negative changes associated with aging. Methods: Using T1 weighted MRI images, we applied a novel algorithm to determine the physiological age of the brain (brain-predicted age) and the predicted age difference between this physiologically based estimate and chronological age (BrainPAD) to 551 sedentary adults aged 65 to 84 with self-reported cognitive complaint measured at baseline as part of a larger study. We also assessed maximal aerobic capacity with a graded exercise test, physical activity and sleep with accelerometers, and body composition with dual energy x-ray absorptiometry. Associations were explored both linearly and logistically using categorical groupings. Results: Visceral Adipose Tissue (VAT), Total Sleep Time (TST) and maximal aerobic capacity all showed significant associations with BrainPAD. Greater VAT was associated with higher (i.e,. older than chronological) BrainPAD (r = 0.149 p = 0.001)Greater TST was associated with higher BrainPAD (r = 0.087 p = 0.042) and greater aerobic capacity was associated with lower BrainPAD (r = - 0.088 p = 0.040). With linear regression, both VAT and TST remained significant (p = 0.036 and 0.008 respectively). Each kg of VAT predicted a 0.741 year increase in BrainPAD, and each hour of increased TST predicted a 0.735 year increase in BrainPAD. Maximal aerobic capacity did not retain statistical significance in fully adjusted linear models. Discussion: Accumulation of visceral adipose tissue and greater total sleep time, but not aerobic capacity, total daily physical activity, or sleep quantity and/or quality are associated with brains that are physiologically older than would be expected based upon chronological age alone (BrainPAD).

Acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder: the FACTOID feasibility study.

BACKGROUND: Generalised anxiety disorder, characterised by excessive anxiety and worry, is the most common anxiety disorder among older people. It is a condition that may persist for decades and is associated with numerous negative outcomes. Front-line treatments include pharmacological and psychological therapy, but many older people do not find these treatments effective. Guidance on managing treatment-resistant generalised anxiety disorder in older people is lacking. OBJECTIVES: To assess whether or not a study to examine the clinical effectiveness and cost-effectiveness of acceptance and commitment therapy for older people with treatment-resistant generalised anxiety disorder is feasible, we developed an intervention based on acceptance and commitment therapy for this population, assessed its acceptability and feasibility in an uncontrolled feasibility study and clarified key study design parameters. DESIGN: Phase 1 involved qualitative interviews to develop and optimise an intervention as well as a survey of service users and clinicians to clarify usual care. Phase 2 involved an uncontrolled feasibility study and qualitative interviews to refine the intervention. SETTING: Participants were recruited from general practices, Improving Access to Psychological Therapies services, Community Mental Health Teams and the community. PARTICIPANTS: Participants were people aged ≥ 65 years with treatment-resistant generalised anxiety disorder. INTERVENTION: Participants received up to 16 one-to-one sessions of acceptance and commitment therapy, adapted for older people with treatment-resistant generalised anxiety disorder, in addition to usual care. Sessions were delivered by therapists based in primary and secondary care services, either in the clinic or at participants' homes. Sessions were weekly for the first 14 sessions and fortnightly thereafter. MAIN OUTCOME MEASURES: The co-primary outcome measures for phase 2 were acceptability (session attendance and satisfaction with therapy) and feasibility (recruitment and retention). Secondary outcome measures included additional measures of acceptability and feasibility and self-reported measures of anxiety, worry, depression and psychological flexibility. Self-reported outcomes were assessed at 0 weeks (baseline) and 20 weeks (follow-up). Health economic outcomes included intervention and resource use costs and health-related quality of life. RESULTS: Fifteen older people with treatment-resistant generalised anxiety disorder participated in phase 1 and 37 participated in phase 2. A high level of feasibility was demonstrated by a recruitment rate of 93% and a retention rate of 81%. A high level of acceptability was found with respect to session attendance (70% of participants attended ≥ 10 sessions) and satisfaction with therapy was adequate (60% of participants scored ≥ 21 out of 30 points on the Satisfaction with Therapy subscale of the Satisfaction with Therapy and Therapist Scale-Revised, although 80% of participants had not finished receiving therapy at the time of rating). Secondary outcome measures and qualitative data further supported the feasibility and acceptability of the intervention. Health economic data supported the feasibility of examining cost-effectiveness in a future randomised controlled trial. Although the study was not powered to examine clinical effectiveness, there was indicative evidence of improvements in scores for anxiety, depression and psychological flexibility. LIMITATIONS: Non-specific therapeutic factors were not controlled for, and recruitment in phase 2 was limited to London. CONCLUSIONS: There was evidence of high levels of feasibility and acceptability and indicative evidence of improvements in symptoms of anxiety, depression and psychological flexibility. The results of this study suggest that a larger-scale randomised controlled trial would be feasible to conduct and is warranted. TRIAL REGISTRATION: Current Controlled Trials ISRCTN12268776. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 54. See the NIHR Journals Library website for further project information.

Generalised anxiety disorder, characterised by a tendency to worry, is the most common anxiety disorder among older people. Those with this condition may experience other difficulties, including increased distress and disability, poorer coping and reduced quality of life. Medication and talking therapy are usually offered as forms of treatment, but many do not find them helpful. Guidance is lacking on how to help older people manage generalised anxiety disorder when it does not respond to such treatments. We developed a 16-session intervention specifically for older people with treatment-resistant generalised anxiety disorder. This was based on acceptance and commitment therapy: a form of talking therapy that helps people to learn how to best live with distressing experiences while still doing things that really matter to them. It may be particularly suited to older people because many older people experience difficulties with chronic ill health and other problems that cannot be easily improved with conventional talking therapies. We developed our intervention by asking 15 older people about their experiences of treatment-resistant generalised anxiety disorder and treatments they have received for it, as well as what might help or hinder their engagement with talking therapy. We combined their guidance with advice from 36 clinicians to ensure that our intervention was tailored to the needs of this population. We then asked the same 15 older people, our Service User Advisory Group and academic clinicians about how we could optimise our intervention. We also conducted an online survey of service users and clinicians to clarify what care older people with generalised anxiety disorder are typically offered and receive. We tested how acceptable our intervention was to 37 older people with treatment-resistant generalised anxiety disorder, and how feasible it was to deliver within the NHS. We found evidence that it was acceptable to participants, that it could be delivered within the NHS and that its value for money could be tested in a larger study. We also found evidence suggestive of improvements in anxiety, depression and coping. There were some limitations of our study. However, overall, our results suggest that we should conduct a larger study to find out whether or not our intervention is helpful for older people with treatment-resistant generalised anxiety disorder.

Acceptance and commitment therapy for late-life treatment-resistant generalised anxiety disorder: a feasibility study.

BACKGROUND: Generalised anxiety disorder (GAD) is the most common anxiety disorder in older people. First-line management includes pharmacological and psychological therapies, but many do not find these effective or acceptable. Little is known about how to manage treatment-resistant generalised anxiety disorder (TR-GAD) in older people. OBJECTIVES: To examine the acceptability, feasibility and preliminary estimates of the effectiveness of acceptance and commitment therapy (ACT) for older people with TR-GAD. PARTICIPANTS: People aged ≥65 years with TR-GAD (defined as not responding to GAD treatment, tolerate it or refused treatment) recruited from primary and secondary care services and the community. INTERVENTION: Participants received up to 16 one-to-one sessions of ACT, developed specifically for older people with TR-GAD, in addition to usual care. MEASUREMENTS: Co-primary outcomes were feasibility (defined as recruitment of ≥32 participants and retention of ≥60% at follow-up) and acceptability (defined as participants attending ≥10 sessions and scoring ≥21/30 on the satisfaction with therapy subscale). Secondary outcomes included measures of anxiety, worry, depression and psychological flexibility (assessed at 0 and 20 weeks). RESULTS: Thirty-seven participants were recruited, 30 (81%) were retained and 26 (70%) attended ≥10 sessions. A total of 18/30 (60%) participants scored ≥21/30 on the satisfaction with therapy subscale. There was preliminary evidence suggesting that ACT may improve anxiety, depression and psychological flexibility. CONCLUSIONS: There was evidence of good feasibility and acceptability, although satisfaction with therapy scores suggested that further refinement of the intervention may be necessary. Results indicate that a larger-scale randomised controlled trial of ACT for TR-GAD is feasible and warranted.

The Association between Age and Experienced Emotions in Hoarding Disorder.

Objectives: Hoarding disorder (HD) is conceptualized as a fear-based disorder and exposure to sorting/discarding possessions is a core part of treatment. However, there has been no investigation of age-related differences in emotional reaction to sorting. The objective of this study was to explore the association between age and affective response during a sorting task.Methods: Forty-nine adults with HD completed a standardized sorting task. Participants reported their current emotion before and after the sorting task and reported their subjective distress throughout the task.Results: Older participants reported significantly lower distress ratings. Only 43% of participants reported fear prior to the task and 22% reported fear after the task. The probability of reporting fear before and after the task decreased significantly with age.Conclusions: Fear may not be the emotion experienced when discarding items, particularly for older adults with HD. Future work should focus on mechanisms of action in HD treatment.Clinical Implications: Clinicians should not assume fear or anxiety to be the primary emotional response in older adults with HD when engaged in an exposure to sorting/discarding. Older hoarding patients with a more fear-oriented aversion to sorting possessions may require a treatment emphasis on increasing the percentage of items discarded.

Guided self-management targeting anxiety and activity participation in older Veterans.

OBJECTIVES: This study examined the acceptance, feasibility, and preliminary effects of a guided self-management intervention using video delivery and a telephone coach on anxiety and activity engagement. METHOD: Ten Veterans aged 60 years or older with anxiety disorders determined by Structured Clinical Interview for Diagnostic and Statistical Manual 5th edition (SCID-5) at baseline visit participated in this non-randomized study examining a 4-week guided self-management intervention for anxiety. Feasibility was examined using participation engagement with the intervention. Measures of anxiety (Geriatric Anxiety Scale, PROMIS Anxiety Scale, Anxiety Control Questionnaire), depression (Patient Health Questionnaire 9-item), and activity participation (modified Activity Card Sort) administered at baseline and final (week 8) visit provided estimates of preliminary intervention effects. The Geriatric Anxiety Scale also was administered by phone at week 4. Participants completed a semi-structured qualitative interview at the final visit, which provided information about the acceptability, benefits of intervention, and barriers to engagement. RESULTS: All participants (N = 10) reported that the intervention somewhat or completely met their expectations, demonstrating intervention acceptability. Intervention completers (n = 9) experienced reduced anxiety over the first 4 weeks, alongside significant improvements in anxiety control and personalized activity goals across 8 weeks. However, anxiety symptoms tended to return to baseline at follow-up. Participants identified the relaxation videos and promotion of a daily relaxation routine as the most helpful intervention components. CONCLUSIONS: Findings indicate that the intervention may improve activity participation and reduce anxiety. Thus, guided self-management interventions show promise for reducing distress and maintaining engagement later in life.

Mindfulness, Education, and Exercise for age-related cognitive decline: Study protocol, pilot study results, and description of the baseline sample.

BACKGROUND/AIMS: Age-related cognitive decline is a pervasive problem in our aging population. To date, no pharmacological treatments to halt or reverse cognitive decline are available. Behavioral interventions, such as physical exercise and Mindfulness-Based Stress Reduction, may reduce or reverse cognitive decline, but rigorously designed randomized controlled trials are needed to test the efficacy of such interventions. METHODS: Here, we describe the design of the Mindfulness, Education, and Exercise study, an 18-month randomized controlled trial that will assess the effect of two interventions-mindfulness training plus moderate-to-vigorous intensity exercise or moderate-to-vigorous intensity exercise alone-compared with a health education control group on cognitive function in older adults. An extensive battery of biobehavioral assessments will be used to understand the mechanisms of cognitive remediation, by using structural and resting state functional magnetic resonance imaging, insulin sensitivity, inflammation, and metabolic and behavioral assessments. RESULTS: We provide the results from a preliminary study (n = 29) of non-randomized pilot participants who received both the exercise and Mindfulness-Based Stress Reduction interventions. We also provide details on the recruitment and baseline characteristics of the randomized controlled trial sample (n = 585). CONCLUSION: When complete, the Mindfulness, Education, and Exercise study will inform the research community on the efficacy of these widely available interventions improve cognitive functioning in older adults.

Does patient expectancy account for the cognitive and clinical benefits of mindfulness training in older adults?

OBJECTIVES: Patient expectations of treatment effects could influence neuropsychological and clinical outcomes in clinical trials of behavioral and lifestyle interventions, which could potentially confound the interpretation of findings. Our aim was to examine whether patient expectancy mediated effectiveness of Mindfulness-Based Stress Reduction (MBSR) for improving cognitive function and clinical outcome. METHODS: The present study uses data from a single-blind, multi-site, randomized controlled trial comparing MBSR to a health education attention control in older adults with anxiety and/or depressive disorders and subjective cognitive concerns. Using the Credibility and Expectations Questionnaire, we measured expectancy and perceived credibility of the interventions assigned to patients. Using mediational analysis, we examined the influence of expectancy and credibility on two key outcomes: memory performance and clinical global improvement. RESULTS: Neither expectancy nor perceived credibility of intervention accounted significantly for MBSR's effectiveness for memory test performance or clinical global improvement. CONCLUSION: In this clinical trial, expectancy for improvement did not account for the effectiveness of MBSR on memory performance or clinical outcomes in depressed and anxious older adults. We advise that clinical trials of behavioral and lifestyle interventions for brain health in older adults should measure and test the role of expectancy.