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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.

[This corrects the article DOI: 10.1371/journal.pone.0152471.].

IntroductionAlzheimer’s disease and related dementias (ADRD) are conditions with progressive cognitive decline. Still, people living with late-stage ADRD (PLWD) have been reported to exhibit transient recovery of communication or behavioural abilities that had seemingly been lost. These lucid episodes (LEs) are underinvestigated and poorly understood. This study aims to advance scientific understanding of the incidence, prevalence and predictors of LEs and assess from family caregivers if LEs are associated with changes they make in care planning or experiences with burden, distress or grief.MethodsThis study recruited 545 caregivers from five ADRD-related registries in the USA. Eligibility included caregivers over 18 years who currently provide care to someone with moderate to very severe ADRD and can complete online questionnaires. Using a longitudinal observational study design, consented caregivers will be assessed monthly for 1 year using online questionnaires that inquire about witnessing LEs. If witnessed, the context and content of the LE is reported. Changes in caregiver decision-making about care for the PLWD, and caregiver burden, distress and grief are assessed at baseline, 6 and 12 months.AnalysisAnalysis of baseline data will assess descriptive aspects of LEs that are currently unknown (eg, prevalence, content, antecedents, duration). Longitudinal analysis will examine the incidence of LEs, characteristics of PLWD and caregivers that are predictors of episodes, and the associations between LEs and caregiver outcomes (eg, burden, distress, grief).Ethics and disseminationThis study is being conducted in accordance with all Federal Policies for the Protection of Human Subjects. The protocol has been approved by the Mayo Clinic Institutional Review Board (ID 22-006861). Findings will be presented at scientific conferences and disseminated through journal publications and outreach efforts with collaborating partners invested in brain health and caregiver support.

In Down syndrome (DS) or trisomy of chromosome 21, the β-amyloid (Aβ) peptide product of the amyloid precursor protein (APP) is present in excess. Evidence points to increased APP gene dose and Aβ as playing a critical role in cognitive difficulties experienced by people with DS. Particularly, Aβ is linked to the late-life emergence of dementia as associated with neuropathological markers of Alzheimer's disease (AD). At present, no treatment targets Aβ-related pathogenesis in people with DS. Herein we used a vaccine containing the Aβ 1-15 peptide embedded into liposomes together with the adjuvant monophosphoryl lipid A (MPLA). Ts65Dn mice, a model of DS, were immunized with the anti-Aβ vaccine at 5 months of age and were examined for cognitive measures at 8 months of age. The status of basal forebrain cholinergic neurons and brain levels of APP and its proteolytic products were measured. Immunization of Ts65Dn mice resulted in robust anti-Aβ IgG titers, demonstrating the ability of the vaccine to break self-tolerance. The vaccine-induced antibodies reacted with Aβ without detectable binding to either APP or its C-terminal fragments. Vaccination of Ts65Dn mice resulted in a modest, but non-significant reduction in brain Aβ levels relative to vehicle-treated Ts65Dn mice, resulting in similar levels of Aβ as diploid (2N) mice. Importantly, vaccinated Ts65Dn mice showed resolution of memory deficits in the novel object recognition and contextual fear conditioning tests, as well as reduction of cholinergic neuron atrophy. No treatment adverse effects were observed; vaccine did not result in inflammation, cellular infiltration, or hemorrhage. These data are the first to show that an anti-Aβ immunotherapeutic approach may act to target Aβ-related pathology in a mouse model of DS.

Backgrounds Digital, online assessments are efficient means to detect early cognitive decline, but few studies have investigated the relationship between remotely collected subjective cognitive change and cognitive decline. We hypothesized that the Everyday Cognition Scale (ECog), a subjective change measure, predicts longitudinal change in cognition in the Brain Health Registry (BHR), an online registry for neuroscience research. Methods This study included BHR participants aged 55 + who completed both the baseline ECog and repeated administrations of the CANTAB ® Paired Associates Learning (PAL) visual learning and memory test. Both self-reported ECog (Self-ECog) and study partner-reported ECog (SP-ECog), and two PAL scores (first attempt memory score [FAMS] and total errors adjusted [TEA]) were assessed. We estimated associations between multiple ECog scoring outputs (ECog positive [same or above cut-off score], ECog consistent [report of consistent decline in any item], and total score) and longitudinal change in PAL. Additionally we assessed the ability of ECog to identify ‘decliners’, who exhibited the worst PAL progression slopes corresponding to the fifth percentile and below. Results Participants ( n  = 16,683) had an average age of 69.07 ± 7.34, 72.04% were female, and had an average of 16.66 ± 2.26 years of education. They were followed for an average of 2.52 ± 1.63 visits over a period of 11.49 ± 11.53 months. Both Self-ECog positive (estimate = -0.01, p  < 0.001, R²m = 0.56) and Self-ECog consistent (estimate=-0.01, p  = 0.002, R²m = 0.56) were associated with longitudinal change in PAL FAMS after adjusting demographics and clinical confounders. Those who were Self-ECog total (Odds ratio [95% confidence interval] = 1.390 [1.121–1.708]) and SP-ECog consistent (2.417 [1.591–3.655]) had higher probability of being decliners based on PAL FAMS. Conclusion In the BHR’s unsupervised online setting, baseline subjective change was feasible in predicting longitudinal decline in neuropsychological tests. Online, self-administered measures of subjective cognitive change might have a potential to predict objective subjective change and identify individuals with cognitive impairments.

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. 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). 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. 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. 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. ClinicalTrials.gov NCT03844321; https://clinicaltrials.gov/ct2/show/NCT03844321.

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.

BACKGROUND This study assessed how medical exclusion criteria of a prevention Alzheimer's disease trial impact potential eligibility and sample characteristics. METHODS Medical exclusion criteria from the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial were applied to N = 3695 participants from the population‐based Health Retirement Study (HRS) with linked Medicare data. We determined the proportion of hypothetical eligibility. Multivariate Poisson regression was used to estimate associations between sociodemographic characteristics and eligibility. RESULTS Of the participants, 74.2% (N = 2742) were deemed ineligible. Accounting for all sociodemographic characteristics, older age, female gender, fewer years of education, lower net worth, and body mass index of 30+ was associated with a higher odds of being deemed ineligible. Ethnocultural identity and living arrangement were not associated with eligibility. CONCLUSIONS Our results suggest that certain sociodemographic factors may limit eligibility for a prevention Alzheimer's disease trial due to the presence of exclusionary medical conditions. This highlights the need to make trials more inclusive. Highlights A total of 2742 participants (74.2%) were deemed ineligible for the Anti‐Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) trial based on the medical exclusion criteria. The most common medical exclusion in this sample was for cardiovascular conditions. Ineligibility was associated with age, education, net worth, and body mass index.

Introduction This study aimed to identify the relationship of sociodemographic variables with older adults participation in an online registry for recruitment and longitudinal assessment in cognitive aging. Methods Using Brain Health Registry (BHR) data, associations between sociodemographic variables (sex, race, ethnicity, education) and registry participation outcomes (task completion, willingness to participate in future studies, referral/enrollment in other studies) were examined in adults aged 55+ (N = 35,919) using logistic regression. All models included sex, race, ethnicity, education, age, and subjective memory concern. Results Non‐white race, being Latino, and lower educational attainment were associated with decreased task completion and enrollment in additional studies. Results for sex were mixed. Discussion The findings provide novel information about engagement in online aging‐related registries, and highlight a need to develop improved engagement strategies targeting underrepresented sociodemographic groups. Increasing registry diversity will allow researchers to refer more representative populations to Alzheimer's and related dementias prevention and treatment trials.

Objective Identifying individuals at risk for cognitive decline, Mild Cognitive Impairment (MCI), and dementia due to Alzheimer’s disease (AD) is a critical need. Functional decline is associated with risk and can be efficiently assessed by participants and study partners (SPs). We tested the hypothesis that SP‐reported functional decline is an independent predictor of dementia risk and cognitive decline. Methods In 1048 older adults in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), we measured associations between Everyday Cognition Scale scores (ECog, self‐ and SP‐reported versions) and (1) baseline and longitudinal change in neuropsychological test (NPT scores) across multiple cognitive domains; (2) diagnostic conversion to MCI or dementia. Models included Mini Mental Status Exam (MMSE) score and ApoE ε4 genotype (APOE) as predictors. Model fits were compared with and without predictors of interest included. Results SP‐reported ECog was the strongest predictor of cognitive decline across multiple domains, as well as diagnostic conversion. Self‐reported ECog was associated with baseline NPT scores in some cognitive domains, and diagnostic conversion to MCI in participants with biomarker evidence for AD (elevated brain β‐amyloid, Aβ). Models including SP‐reported ECog were significantly stronger at predicting outcomes. Conclusions SP‐reported functional decline is an independent indicator of cognitive decline and dementia risk, even when accounting for cognitive screening, genetic risk, demographics, and self‐report decline. The results provide a rationale for greater utilization of SP‐reported functional decline to identify those at risk for dementia due to AD and other causes.