Development and validation of an episodic memory measure in the Mobile Toolbox (MTB): Arranging Pictures.

INTRODUCTION: Arranging Pictures is a new episodic memory test based on the NIH Toolbox (NIHTB) Picture Sequence Memory measure and optimized for self-administration on a personal smartphone within the Mobile Toolbox (MTB). We describe evidence from three distinct validation studies. METHOD: In Study 1, 92 participants self-administered Arranging Pictures on study-provided smartphones in the lab and were administered external measures of similar and dissimilar constructs by trained examiners to assess validity under controlled circumstances. In Study 2, 1,021 participants completed the external measures in the lab and self-administered Arranging Pictures remotely on their personal smartphones to assess validity in real-world contexts. In Study 3, 141 participants self-administered Arranging Pictures remotely twice with a two-week delay on personal iOS smartphones to assess test-retest reliability and practice effects. RESULTS: Internal consistency was good across samples (ρxx = .80 to .85, p < .001). Test-retest reliability was marginal (ICC = .49, p < .001) and there were significant practice effects after a two-week delay (ΔM = 3.21 (95% CI [2.56, 3.88]). As expected, correlations with convergent measures were significant and moderate to large in magnitude (ρ = .44 to .76, p < .001), while correlations with discriminant measures were small (ρ = .23 to .27, p < .05) or nonsignificant. Scores demonstrated significant negative correlations with age (ρ = -.32 to -.21, p < .001). Mean performance was slightly higher in the iOS compared to the Android group (MiOS = 18.80, NiOS = 635; MAndroid = 17.11, NAndroid = 386; t(757.73) = 4.17, p < .001), but device type did not significantly influence the psychometric properties of the measure. Indicators of potential cheating were mixed; average scores were significantly higher in the remote samples (F(2, 850) = 11.415, p < .001), but there were not significantly more perfect scores. CONCLUSION: The MTB Arranging Pictures measure demonstrated evidence of reliability and validity when self-administered on personal device. Future research should examine the potential for cheating in remote settings and the properties of the measure in clinical samples.

Remote olfactory assessment using the NIH Toolbox Odor Identification test and the brain health registry.

BACKGROUND: Early identification of deficits in our ability to perceive odors is important as many normal (i.e., aging) and pathological (i.e., sinusitis, viral, neurodegeneration) processes can result in diminished olfactory function. To realistically enable population-level measurements of olfaction, validated olfaction tests must be capable of being administered outside the research laboratory and clinical setting. AIM: The purpose of this study was to determine the feasibility of remotely testing olfactory performance using a test that was developed with funding from the National Institutes of Health as part of a ready-to-use, non-proprietary set of measurements useful for epidemiologic studies (NIH Toolbox Odor ID Test). MATERIALS AND METHODS: Eligible participants older than 39 years and active (within 6 months) in the Brain Health Registry (BHR), an online cognitive assessment platform which connects participants with researchers, were recruited for this study. Interested participants were mailed the NIH Toolbox Odor ID Test along with instructions on accessing a website to record their responses. Data obtained from subjects who performed the test at home was compared to the normative data collected when the NIH Toolbox Odor ID Test was administered by a tester in a research setting and validated against the Smell Identification Test. The age-range and composition of the population ensured we had the ability to observe both age-related decline and gender-related deficits in olfactory ability, as shown in the experimental setting. RESULTS: We observed that age-associated olfactory decline and gender-associated performance was comparable to performance on the administered test. Self-administration of this test showed the age-related loss in olfactory acuity, F(4, 1156)=14.564, p<.0001 as well as higher accuracy for women compared to men after controlling for participants' age, F(1, 1160) = 22.953, p <.0001. The effect size calculated as Hedge's g, was 0.41. CONCLUSION: These results indicate that the NIH Toolbox Odor ID Test is an appropriate instrument for self-administered assessment of olfactory performance. The ability to self-administer an inexpensive olfactory test increases its utility for inclusion in longitudinal epidemiological studies and when in-person testing is not feasible.

Development and Validation of a Vocabulary Measure in the Mobile Toolbox.

OBJECTIVE: We describe the development of a new computer adaptive vocabulary test, Mobile Toolbox (MTB) Word Meaning, and validity evidence from 3 studies. METHOD: Word Meaning was designed to be a multiple-choice synonym test optimized for self-administration on a personal smartphone. The items were first calibrated online in a sample of 7,525 participants to create the computer-adaptive test algorithm for the Word Meaning measure within the MTB app. In Study 1, 92 participants self-administered Word Meaning on study-provided smartphones in the lab and were administered external measures by trained examiners. In Study 2, 1,021 participants completed the external measures in the lab and Word Meaning was self-administered remotely on their personal smartphones. In Study 3, 141 participants self-administered Word Meaning remotely twice with a 2-week delay on personal iPhones. RESULTS: The final bank included 1363 items. Internal consistency was adequate to good across samples (ρxx = 0.78 to 0.81, p < .001). Test-retest reliability was good (ICC = 0.65, p < .001), and the mean theta score was not significantly different upon the second administration. Correlations were moderate to large with measures of similar constructs (ρ = 0.67-0.75, p < .001) and non-significant with measures of dissimilar constructs. Scores demonstrated small to moderate correlations with age (ρ = 0.35 to 0.45, p < .001) and education (ρ = 0.26, p < .001). CONCLUSION: The MTB Word Meaning measure demonstrated evidence of reliability and validity in three samples. Further validation studies in clinical samples are necessary.

Participant completion of longitudinal assessments in an online cognitive aging registry: The role of medical conditions.

INTRODUCTION: This study aimed to understand whether older adults' longitudinal completion of assessments in an online Alzheimer's disease and related dementias (ADRD)-related registry is influenced by self-reported medical conditions. METHODS: Brain Health Registry (BHR) is an online cognitive aging and ADRD-related research registry that includes longitudinal health and cognitive assessments. Using logistic regressions, we examined associations between longitudinal registry completion outcomes and self-reported (1) number of medical conditions and (2) eight defined medical condition groups (cardiovascular, metabolic, immune system, ADRD, current psychiatric, substance use/abuse, acquired, other specified conditions) in adults aged 55+ (N = 23,888). Longitudinal registry completion outcomes were assessed by the completion of the BHR initial questionnaire (first questionnaire participants see at each visit) at least twice and completion of a cognitive assessment (Cogstate Brief Battery) at least twice. Models included ethnocultural identity, education, age, and subjective memory concern as covariates. RESULTS: We found that the likelihood of longitudinally completing the initial questionnaire was negatively associated with reporting a diagnosis of ADRD and current psychiatric conditions but was positively associated with reporting substance use/abuse and acquired medical conditions. The likelihood of longitudinally completing the cognitive assessment task was negatively associated with number of reported medical conditions, as well as with reporting cardiovascular conditions, ADRD, and current psychiatric conditions. Previously identified associations between ethnocultural identity and longitudinal assessment completion in BHR remained after accounting for the presence of medical conditions. DISCUSSION: This post hoc analysis provides novel, initial evidence that older adults' completion of longitudinal assessments in an online registry is associated with the number and types of participant-reported medical conditions. Our findings can inform future efforts to make online studies with longitudinal health and cognitive assessments more usable for older adults with medical conditions. The results need to be interpreted with caution due to selection biases, and the under-inclusion of minoritized communities.

The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.

The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to improve Alzheimer's disease (AD) clinical trials. Since 2006, ADNI has shared clinical, neuroimaging, and cognitive data, and biofluid samples. We used conventional search methods to identify 1459 publications from 2021 to 2022 using ADNI data/samples and reviewed 291 impactful studies. This review details how ADNI studies improved disease progression understanding and clinical trial efficiency. Advances in subject selection, detection of treatment effects, harmonization, and modeling improved clinical trials and plasma biomarkers like phosphorylated tau showed promise for clinical use. Biomarkers of amyloid beta, tau, neurodegeneration, inflammation, and others were prognostic with individualized prediction algorithms available online. Studies supported the amyloid cascade, emphasized the importance of neuroinflammation, and detailed widespread heterogeneity in disease, linked to genetic and vascular risk, co-pathologies, sex, and resilience. Biological subtypes were consistently observed. Generalizability of ADNI results is limited by lack of cohort diversity, an issue ADNI-4 aims to address by enrolling a diverse cohort.

Relationship of Hoarding and Depression Symptoms in Older Adults.

Hoarding disorder (HD) is a debilitating neuropsychiatric condition that affects 2%-6% of the population and increases in incidence with age. Major depressive disorder (MDD) co-occurs with HD in approximately 50% of cases and leads to increased functional impairment and disability. However, only one study to date has examined the rate and trajectory of hoarding symptoms in older individuals with a lifetime history of MDD, including those with current active depression (late-life depression; LLD). We therefore sought to characterize this potentially distinct phenotype. We determined the incidence of HD in two separate cohorts of participants with LLD (n = 73) or lifetime history of MDD (n = 580) and examined the reliability and stability of hoarding symptoms using the Saving Inventory-Revised (SI-R) and Hoarding Rating Scale-Self Report (HRS), as well as the co-variance of hoarding and depression scores over time. HD was present in 12% to 33% of participants with MDD, with higher rates found in those with active depressive symptoms. Hoarding severity was stable across timepoints in both samples (all correlations >0.75), and fewer than 30% of participants in each sample experienced significant changes in severity between any two timepoints. Change in depression symptoms over time did not co-vary with change in hoarding symptoms. These findings indicate that hoarding is a more common comorbidity in LLD than previously suggested, and should be considered in screening and management of LLD. Future studies should further characterize the interaction of these conditions and their impact on outcomes, particularly functional impairment in this vulnerable population.

Brain Health Registry Study Partner Portal: Novel infrastructure for digital, dyadic data collection.

BACKGROUND: In Alzheimer's disease (AD) research, subjective reports of cognitive and functional decline from participant-study partner dyads is an efficient method of assessing cognitive impairment and clinical progression. METHODS: Demographics and subjective cognitive/functional decline (Everyday Cognition Scale [ECog]) scores from dyads enrolled in the Brain Health Registry (BHR) Study Partner Portal were analyzed. Associations between dyad characteristics and both ECog scores and study engagement were investigated. RESULTS: A total of 10,494 BHR participants (mean age = 66.9 ± 12.16 standard deviations, 67.4% female) have enrolled study partners (mean age = 64.3 ± 14.3 standard deviations, 49.3% female), including 8987 dyads with a participant 55 years of age or older. Older and more educated study partners were more likely to complete tasks and return for follow-up. Twenty-five percent to 27% of older adult participants had self and study partner-report ECog scores indicating a possible cognitive impairment. DISCUSSION: The BHR Study Partner Portal is a unique digital tool for capturing dyadic data, with high impact applications in the clinical neuroscience and AD fields. Highlights The Brain Health Registry (BHR) Study Partner Portal is a novel, digital platform of >10,000 dyads. Collection of dyadic online subjective cognitive and functional data is feasible. The portal has good usability as evidenced by positive study partner feedback. The portal is a potential scalable strategy for cognitive impairment screening in older adults.

Evaluation of the Electronic Clinical Dementia Rating for Dementia Screening.

Importance: The Clinical Dementia Rating (CDR) is a well-validated instrument widely used to detect and stage dementia due to Alzheimer disease. The digital Electronic Clinical Dementia Rating (eCDR) can be remotely self-administered and automatically scored, with potential to facilitate efficient dementia screening and staging. Objective: To evaluate the association of the eCDR with the CDR and other in-clinic assessments for screening older adults for cognitive impairment. Design, Setting, and Participants: This multisite, cross-sectional study used baseline data from a longitudinal, observational study from 2020 to 2023, including up to 3 years of follow-up. Participants were enrolled from 3 Alzheimer Disease Research Centers and the Brain Health Registry. Participants (aged ≥55 years, with a study partner, and no acute or unstable major medical conditions) were recruited during in-clinic visits or by automated emails. Exposures: Participants completed the Uniform Data Set Version 3 (UDS; including the CDR) in supervised clinical research settings, and then completed the eCDR remotely, online and unsupervised, using their own device. Main Outcomes and Measures: The primary outcomes were eCDR scores (item; categorical box and global; continuous box and global), CDR scores (item; categorical box and global), and UDS assessment scores. Associations were evaluated using linear and logistic regressions. Results: A total of 3565 participants were contacted, and 288 were enrolled. Among 173 participants with item-level data (mean [SD] age, 70.84 [7.65] years; 76 women [43.9%]), eCDR to CDR concordance was 90% or higher for 33 items (63%) and 70% to 89% for 13 items (25%). Box (domain) level concordance ranged from 80% (memory) to 99% (personal care). The global score concordance rate was 81%. κ statistics were fair to moderate. Among 206 participants with box and global scores (mean [SD] age, 71.34 [7.68] years; 95 women [46.1%]), eCDR continuous global score was associated with CDR global (categorical) score with an area under the receiver operating characteristic curve of 0.79 (95% CI, 0.70-0.87). Correlations between eCDR and in-clinic UDS assessments were similar to those between CDR sum of box scores and the same in-clinic assessments. Conclusions and Relevance: These findings suggest that the eCDR is valid and has potential use for screening and assessment of older adults for cognitive and functional decline related to Alzheimer disease. Instrument optimization and validation in diverse cohorts in remote settings are crucial for evaluating scalability and eCDR utility in clinical research, trials, and health care settings.

How intention to join an Alzheimer's participant recruitment registry differs by race, ethnicity, sex, and family history: Results from a national survey of US adults.

INTRODUCTION: Alzheimer's-focused participant recruitment registries are tools for accelerating enrollment into studies, however, registry members are primarily White women. METHODS: We conducted a national online survey of 1501 adults ages 50-80, oversampling for Black and Hispanic/Latino respondents, assessing intention to join a generic "brain health" registry and to join a registry that required specific tasks. RESULTS: Intention to join a registry was low (M 3.48, SD 1.77), and lower than intention to join a registry requiring specific tasks. Intention was greatest for registries requiring completing surveys (M 4.70, SD 1.77). Differences in intention were primarily between White women and Black women; differences between other groups were limited to specific tasks required. DISCUSSION: The results indicate uncertainty about what a registry is, its purpose, and/or the concept of "brain health." Using the Reasoned Action Approach (RAA) to develop evidence-based outreach messages describing a registry and required tasks may increase diversity.

Brain health registry updates: An online longitudinal neuroscience platform.

INTRODUCTION: Remote, internet-based methods for recruitment, screening, and longitudinally assessing older adults have the potential to facilitate Alzheimer's disease (AD) clinical trials and observational studies. METHODS: The Brain Health Registry (BHR) is an online registry that includes longitudinal assessments including self- and study partner-report questionnaires and neuropsychological tests. New initiatives aim to increase inclusion and engagement of commonly underincluded communities using digital, community-engaged research strategies. New features include multilingual support and biofluid collection capabilities. RESULTS: BHR includes > 100,000 participants. BHR has made over 259,000 referrals resulting in 25,997 participants enrolled in 30 aging and AD studies. In addition, 28,278 participants are coenrolled in BHR and other studies with data linkage among studies. Data have been shared with 28 investigators. Recent efforts have facilitated the enrollment and engagement of underincluded ethnocultural communities. DISCUSSION: The major advantages of the BHR approach are scalability and accessibility. Challenges include compliance, retention, cohort diversity, and generalizability. HIGHLIGHTS: Brain Health Registry (BHR) is an online, longitudinal platform of > 100,000 members. BHR made > 259,000 referrals, which enrolled 25,997 participants in 32 studies. New efforts increased enrollment and engagement of underincluded communities in BHR. The major advantages of the BHR approach are scalability and accessibility. BHR provides a unique adjunct for clinical neuroscience research.

Improving generalizability and study design of Alzheimer's disease cohort studies in the United States by including under-represented populations.

The poor generalizability of clinical research data due to the enrollment of highly educated, non-Latinx White participants hampers the development of therapies for Alzheimer's disease (AD). Black and Latinx older adults have a greater risk for dementia, yet it is unclear how health-care disparities and sociocultural factors influence potential AD therapies and prognosis. Low enrollment of under-represented populations may be attributable to several factors including greater exclusion due to higher rates of comorbidities, lower access to AD clinics, and the legacy of unethical treatment in medical research. This perspective outlines solutions tested in the Brain Health Registry (BHR) and the Alzheimer's Disease Neuroimaging Initiative (ADNI), including culturally-informed digital research methods, community-engaged research strategies, leadership from under-represented communities, and the reduction of exclusion criteria based on comorbidities. Our successes demonstrate that it is possible to increase the inclusion and engagement of under-represented populations into US-based clinical studies, thereby increasing the generalizability of their results.

Association of Major Depressive Disorder with remotely administered measures of cognition and subjective report of cognitive difficulties across the adult age spectrum.

BACKGROUND: Major depressive disorder (MDD) has increasing prevalence with age. Both objective measures of cognitive dysfunction and subjective report of cognitive difficulties related to MDD are often thought to worsen with increasing age. However, few studies have directly evaluated these characteristics across the adult lifespan. METHODS: Participants included 23,594 adults completing objective and subjective measures of cognition on an online research registry. Linear regression including interactions of age group with depression was used to evaluate the association of self-reported MDD with measures of cognition in three age groups: 21-40 years; 41-60 years; 61+ years. RESULTS: MDD (n = 2127) demonstrated poorer objective cognitive performance and greater subjective ratings of cognitive difficulties across all domains assessed compared to non-depressed individuals (ND; n = 21,467). Significant interactions of age group and MDD status with objective and subjective measures of cognition were observed for both middle age and older adults when compared to young adults but few significant differences between middle-aged and older adults were evident. LIMITATIONS: This study relied on self-report of MDD diagnosis, utilized remotely administered and unsupervised measures of cognition, and the sample was not diverse. CONCLUSIONS: The magnitude of association between MDD and cognitive correlates appears to plateau in middle age. Our results suggest that increased rates of dementia are not due to greater cognitive consequence of MDD in older adults and that age effects, and not greater effects of depression, may lead to increased diagnosis of MDD based on subjective report of cognitive symptoms.

Increasing participant diversity in AD research: Plans for digital screening, blood testing, and a community-engaged approach in the Alzheimer's Disease Neuroimaging Initiative 4.

INTRODUCTION: The Alzheimer's Disease Neuroimaging Initiative (ADNI) aims to validate biomarkers for Alzheimer's disease (AD) clinical trials. To improve generalizability, ADNI4 aims to enroll 50-60% of its new participants from underrepresented populations (URPs) using new biofluid and digital technologies. ADNI4 has received funding from the National Institute on Aging beginning September 2022. METHODS: ADNI4 will recruit URPs using community-engaged approaches. An online portal will screen 20,000 participants, 4000 of whom (50-60% URPs) will be tested for plasma biomarkers and APOE. From this, 500 new participants will undergo in-clinic assessment joining 500 ADNI3 rollover participants. Remaining participants (∼3500) will undergo longitudinal plasma and digital cognitive testing. ADNI4 will add MRI sequences and new PET tracers. Project 1 will optimize biomarkers in AD clinical trials. RESULTS AND DISCUSSION: ADNI4 will improve generalizability of results, use remote digital and blood screening, and continue providing longitudinal clinical, biomarker, and autopsy data to investigators.

Digital culturally tailored marketing for enrolling Latino participants in a web-based registry: Baseline metrics from the Brain Health Registry.

INTRODUCTION: This culturally tailored enrollment effort aims to determine the feasibility of enrolling 5000 older Latino adults from California into the Brain Health Registries (BHR) over 2.25 years. METHODS: This paper describes (1) the development and deployment of culturally tailored BHR websites and digital ads, in collaboration with a Latino community science partnership board and a marketing company; (2) an interim feasibility analysis of the enrollment efforts and numbers, and participant characteristics (primary aim); as well as (3) an exploration of module completion and a preliminary efficacy evaluation of the culturally tailored digital efforts compared to BHR's standard non-culturally tailored efforts (secondary aim). RESULTS: In 12.5 months, 3603 older Latino adults were enrolled (71% of the total California Latino BHR initiative enrollment goal). Completion of all BHR modules was low (6%). DISCUSSION: Targeted ad placement, culturally tailored enrollment messaging, and culturally tailored BHR websites increased enrollment of Latino participants in BHR, but did not translate to increased module completion. HIGHLIGHTS: Culturally tailored social marketing and website improvements were implemented. The efforts enrolled 5662 Latino individuals in 12.5 months. The number of Latino Brain Health Registry (BHR) participants increased by 122.7%. We failed to adequately enroll female Latinos and Latinos with lower education. Future work will evaluate effects of a newly released Spanish-language BHR website.

Poor Sleep Quality and Daytime Fatigue Are Associated With Subjective but Not Objective Cognitive Functioning in Clinically Relevant Hoarding.

Background: Hoarding disorder is a chronic psychiatric condition of increasing public health concern. Recent investigation suggests a positive association between hoarding severity and insomnia symptoms. However, these findings have yet to be replicated, and the prevalence and type of sleep impairment experienced by individuals with clinically relevant hoarding symptoms (CHSs) are not known. Methods: This analysis of 20,473 members of the internet-based Brain Health Registry uses multivariate logistic regression modeling and structural equation modeling to evaluate the relationship between hoarding symptoms, sleep impairment, adverse health, and cognitive functioning. Results: More than 12% of study participants endorsed CHSs or subclinical hoarding symptoms. After adjustment for demographic characteristics and psychiatric comorbidity, individuals with CHSs reported increased odds of sleep impairment in nearly all domains. The odds of poor sleep quality (adjusted odds ratio, 2.07; 95% CI, 1.83-2.34), sleep disturbances (adjusted odds ratio, 2.15; 95% CI, 1.91-2.43), and daytime dysfunction (adjusted odds ratio, 5.84; 95% CI, 5.12-6.65) were two- to fivefold higher for individuals with CHSs compared with those without. For all measures, the proportion of individuals reporting sleep impairment increased with hoarding severity. In our structural equation model, sleep impairment acted as a partial mediator on the indirect pathways from hoarding to subjective cognitive complaints and poorer quality of life. Conclusions: Identification of sleep problems among those with hoarding symptoms is a critical component of hoarding assessment. Additional research is needed to better understand the mechanisms underlying the observed relationships, including neurobiological underpinnings, and to examine the role of sleep management in treatment for hoarding behaviors.

The role of dyadic cognitive report and subjective cognitive decline in early ADRD clinical research and trials: Current knowledge, gaps, and recommendations.

Efficient identification of cognitive decline and Alzheimer's disease (AD) risk in early stages of the AD disease continuum is a critical unmet need. Subjective cognitive decline is increasingly recognized as an early symptomatic stage of AD. Dyadic cognitive report, including subjective cognitive complaints (SCC) from a participant and an informant/study partner who knows the participant well, represents an accurate, reliable, and efficient source of data for assessing risk. However, the separate and combined contributions of self- and study partner report, and the dynamic relationship between the two, remains unclear. The Subjective Cognitive Decline Professional Interest Area within the Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment convened a working group focused on dyadic patterns of subjective report. Group members identified aspects of dyadic-report information important to the AD research field, gaps in knowledge, and recommendations. By reviewing existing data on this topic, we found evidence that dyadic measures are associated with objective measures of cognition and provide unique information in preclinical and prodromal AD about disease stage and progression and AD biomarker status. External factors including dyad (participant-study partner pair) relationship and sociocultural factors contribute to these associations. We recommend greater dyad report use in research settings to identify AD risk. Priority areas for future research include (1) elucidation of the contributions of demographic and sociocultural factors, dyad type, and dyad relationship to dyad report; (2) exploration of agreement and discordance between self- and study partner report across the AD syndromic and disease continuum; (3) identification of domains (e.g., memory, executive function, neuropsychiatric) that predict AD risk outcomes and differentiate cognitive impairment due to AD from other impairment; (4) development of best practices for study partner engagement; (5) exploration of study partner report as AD clinical trial endpoints; (6) continued development, validation, and optimization, of study partner report instruments tailored to the goals of the research and population.

Hoarding symptoms are associated with higher rates of disability than other medical and psychiatric disorders across multiple domains of functioning.

BACKGROUND: Hoarding symptoms are associated with functional impairment, though investigation of disability among individuals with hoarding disorder has largely focused on clutter-related impairment to home management activities and difficulties using space because of clutter. This analysis assesses disability among individuals with hoarding symptoms in multiple domains of everyday functioning, including cognition, mobility, self-care, interpersonal and community-level interactions, and home management. The magnitude of the association between hoarding and disability was compared to that of medical and psychiatric disorders with documented high disability burden, including major depressive disorder (MDD), diabetes, and chronic pain. METHODS: Data were cross-sectionally collected from 16,312 adult participants enrolled in an internet-based research registry, the Brain Health Registry. Pearson's chi-square tests and multivariable logistic regression models were used to quantify the relationship between hoarding and functional ability relative to MDD, diabetes, and chronic pain. RESULTS: More than one in ten participants endorsed clinical (5.7%) or subclinical (5.7%) hoarding symptoms (CHS and SCHS, respectively). After adjusting for participant demographic characteristics and psychiatric and medical comorbidity, CHS and SCHS were associated with increased odds of impairment in all domains of functioning. Moderate to extreme impairment was endorsed more frequently by those with CHS or SCHS compared to those with self-reported MDD, diabetes, and/or chronic pain in nearly all domains (e.g., difficulty with day-to-day work or school: CHS: 18.7% vs. MDD: 11.8%, p < 0.0001) except mobility and self-care. While those with current depressive symptoms endorsed higher rates of impairment than those with hoarding symptoms, disability was most prevalent among those endorsing both hoarding and comorbid depressive symptoms. CONCLUSIONS: Hoarding symptoms are associated with profound disability in all domains of functioning. The burden of hoarding is comparable to that of other medical and psychiatric illnesses with known high rates of functional impairment. Future studies should examine the directionality and underlying causality of the observed associations, and possibly identify target interventions to minimize impairment associated with hoarding symptomatology.

Identifying psychiatric and neurological comorbidities associated with hoarding disorder through network analysis.

BACKGROUND: The relationships between hoarding disorder (HD) and other neurological and psychiatric disorders remain largely unknown. Although psychiatric burden in those with HD is high, less is known about neurological disorders. Furthermore, which disorders are primarily associated with HD vs which can be better explained via a relationship with another disorder has not been determined. To address these questions, we examined comorbidity patterns of psychiatric and neurological disorders in a large online registry of adults using network analyses. METHODS: We first examined psychiatric comorbidity among 252 participants completing clinician administered psychiatric assessments. Using the Brain Health Registry (BHR) (N = 15,978), we next analyzed prevalence of self-reported neurological and psychiatric disorders among participants with no/minimal hoarding, subclinical hoarding, and clinically significant hoarding and used network analyses to identify direct and indirect relationships between HD and the assessed psychiatric and neurological disorders. RESULTS: The most prevalent comorbidity in clinically assessed participants with HD was major depressive disorder (MDD, 62%), followed by generalized anxiety disorder (GAD, 32%). Network analyses in the BHR indicated that the strongest direct relationships with HD were attention-deficit hyperactivity disorder (ADHD), major depressive disorder (MDD), and obsessive-compulsive disorder (OCD). The relationships between HD and neurological disorders, including mild cognitive impairment, were weak or non-existent after controlling for other disorders. CONCLUSIONS: ADHD, MDD, and OCD form a triad of psychiatric disorders directly associated with HD. Despite their high comorbidity rates, the associations among anxiety disorders and HD were weak or indirect.

Web-Based Mindfulness-Based Interventions for Well-being: Randomized Comparative Effectiveness Trial.

BACKGROUND: Mindfulness can improve overall well-being by training individuals to focus on the present moment without judging their thoughts. However, it is unknown how much mindfulness practice and training are necessary to improve well-being. OBJECTIVE: The primary aim of this study was to determine whether a standard 8-session web-based mindfulness-based cognitive therapy (MBCT) program, compared with a brief 3-session mindfulness intervention, improved overall participant well-being. In addition, we sought to explore whether the treatment effects differed based on the baseline characteristics of the participants (ie, moderators). METHODS: Participants were recruited from 17 patient-powered research networks, web-based communities of stakeholders interested in a common research area. Participants were randomized to either a standard 8-session MBCT or a brief 3-session mindfulness training intervention accessed on the web. The participants were followed for 12 weeks. The primary outcome of the study was well-being, as measured by the World Health Organization-Five Well-Being Index. We hypothesized that MBCT would be superior to a brief mindfulness training. RESULTS: We randomized 4411 participants, 3873 (87.80%) of whom were White and 3547 (80.41%) of female sex assigned at birth. The mean baseline World Health Organization-Five Well-Being Index score was 50.3 (SD 20.7). The average self-reported well-being in each group increased over the intervention period (baseline to 8 weeks; model-based slope for the MBCT group: 0.78, 95% CI 0.63-0.93, and brief mindfulness group: 0.76, 95% CI 0.60-0.91) as well as the full study period (ie, intervention plus follow-up; baseline to 20 weeks; model-based slope for MBCT group: 0.41, 95% CI 0.34-0.48; and brief mindfulness group: 0.33, 95% CI 0.26-0.40). Changes in self-reported well-being were not significantly different between MBCT and brief mindfulness during the intervention period (model-based difference in slopes: -0.02, 95% CI -0.24 to 0.19; P=.80) or during the intervention period plus 12-week follow-up (-0.08, 95% CI -0.18 to 0.02; P=.10). During the intervention period, younger participants (P=.05) and participants who completed a higher percentage of intervention sessions (P=.005) experienced greater improvements in well-being across both interventions, with effects that were stronger for participants in the MBCT condition. Attrition was high (ie, 2142/4411, 48.56%), which is an important limitation of this study. CONCLUSIONS: Standard MBCT improved well-being but was not superior to a brief mindfulness intervention. This finding suggests that shorter mindfulness programs could yield important benefits across the general population of individuals with various medical conditions. Younger people and participants who completed more intervention sessions reported greater improvements in well-being, an effect that was more pronounced for participants in the MBCT condition. This finding suggests that standard MBCT may be a better choice for younger people as well as treatment-adherent individuals. TRIAL REGISTRATION: ClinicalTrials.gov NCT03844321; https://clinicaltrials.gov/ct2/show/NCT03844321.

Putting participants and study partners FIRST when clinical trials end early.

Between 2018 and 2019, multiple clinical trials ended earlier than planned, resulting in calls to improve communication with and support for participants and their study partners ("dyads"). The multidisciplinary Participant Follow-Up Improvement in Research Studies and Trials (Participant FIRST) Work Group met throughout 2021. Its goals were to identify best practices for communicating with and supporting dyads affected by early trial stoppage. The Participant FIRST Work Group identified 17 key recommendations spanning the pre-trial, mid-trial, and post-trial periods. These focus on prospectively allocating sufficient resources for orderly closeout; developing dyad-centered communication plans; helping dyads build and maintain support networks; and, if a trial stops, informing dyads rapidly. Participants and study partners invest time, effort, and hope in their research participation. The research community should take intentional steps toward better communicating with and supporting participants when clinical trials end early. The Participant FIRST recommendations are a practical guide for embarking on that journey.