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.

Item Response Analysis of the Financial Capacity Instrument-Short Form.

OBJECTIVE: The Financial Capacity Instrument-Short Form (FCI-SF) is a performance-based measure of everyday financial skills that takes 15 min to administer. Although the FCI-SF has demonstrated excellent psychometric properties, advanced psychometric methods such as item response theory (IRT) can provide important information on the performance of individual test items in measuring financial capacity and in distinguishing between healthy and cognitively impaired individuals. METHOD: Participants were 272 older adults diagnosed with mild cognitive impairment (MCI) and 1,344 cognitively healthy controls recruited from the Mayo Clinic Study of Aging at the Mayo Clinic in Rochester, Minnesota and also from the Cognitive Observations in Seniors study at the University of Alabama at Birmingham. Participants in each study were administered the FCI-SF, which evaluates coin/currency calculation, financial conceptual knowledge, use of a checkbook/register, and use of a bank statement. RESULTS: A unidimensional two-parameter logistic model best fit the 37 FCI-SF Test items, and most FCI-SF items fit the unidimensional two-parameter model well. The results indicated that all FCI-SF items robustly distinguished cognitively healthy controls from persons with MCI. CONCLUSIONS: The study results showed that the FCI-SF performed well under IRT analysis, further highlighted the psychometric properties of the FCI-SF as a valid and reliable measure of financial capacity, and demonstrated the clinical utility of the FCI-SF in distinguishing between cognitively normal and cognitively impaired individuals.

Development and implementation of an electronic Clinical Dementia Rating and Financial Capacity Instrument-Short Form.

Introduction: To address the need for remote assessments of cognitive decline and dementia, we developed and administered electronic versions of the Clinical Dementia Rating (CDR®) and the Financial Capacity Instrument-Short Form (FCI-SF) (F-CAP®), called the eCDR and eFCI, respectively. Methods: The CDR and FCI-SF were adapted for remote, unsupervised, online use based on item response analysis of the standard instruments. Participants completed the eCDR and eFCI first in clinic, and then at home within 2 weeks. Results: Of the 243 enrolled participants, 179 (73%) cognitively unimpaired (CU), 50 (21%) with mild cognitive impairment (MCI) or dementia, and 14 (6%) with an unknown diagnosis, 84% and 85% of them successfully completed the eCDR and eFCI, respectively, at home. Discussion: These results show initial feasibility in developing and administering online instruments to remotely assess and monitor cognitive decline along the CU to MCI/very mild dementia continuum. Validation is an important next step.

Remote blood collection from older adults in the Brain Health Registry for plasma biomarker and genetic analysis.

INTRODUCTION: Use of online registries to efficiently identify older adults with cognitive decline and Alzheimer's disease (AD) is an approach with growing evidence for feasibility and validity. Linked biomarker and registry data can facilitate AD clinical research. METHODS: We collected blood for plasma biomarker and genetic analysis from older adult Brain Health Registry (BHR) participants, evaluated feasibility, and estimated associations between demographic variables and study participation. RESULTS: Of 7150 participants invited to the study, 864 (12%) enrolled and 629 (73%) completed remote blood draws. Participants reported high study acceptability. Those from underrepresented ethnocultural and educational groups were less likely to participate. DISCUSSION: This study demonstrates the challenges of remote blood collection from a large representative sample of older adults. Remote blood collection from > 600 participants within a short timeframe demonstrates the feasibility of our approach, which can be expanded for efficient collection of plasma AD biomarker and genetic data.

Dutch Brain Research Registry for study participant recruitment: Design and first results.

INTRODUCTION: The Dutch Brain Research Registry aims to facilitate online recruitment of participants for brain disease studies. METHODS: Registrants were primarily recruited through an online social media campaign. The registration process included a short questionnaire, which was subsequently used in the prescreening process to match participants to studies. RESULTS: In the first 18 months, 17,218 registrants signed up (58±11 years old, 78% female). Out of 34,696 study invitations that were sent, 36% were accepted by registrants, of which 50% to 84% were finally enrolled, resulting in 10,661 participants in 28 studies. Compared to non-participants, study participants were more often older, male, more highly educated, retired or unemployed, non-smoking, healthier, and more often had a family member with dementia. DISCUSSION: The Dutch Brain Research Registry facilitates effective matching of participants to brain disease studies. Participant factors related to study enrollment may reflect facilitators or barriers for participation, which is useful for improving recruitment strategies.

Beneficial effects of glatiramer acetate in Huntington's disease mouse models: Evidence for BDNF-elevating and immunomodulatory mechanisms.

Huntington's disease (HD) is a fatal, neurodegenerative movement disorder that has no cure and few treatment options. In these preclinical studies, we tested the effects of chronic treatment of glatiramer acetate (GA; Copaxone®), an FDA-approved drug used as first-line therapy for MS, in two different HD mouse models, and explored potential mechanisms of action of drug efficacy. Groups of CAG140 knock-in and N171-82Q transgenic mice were treated with GA for up to 1year of age (CAG140 knock-in mice) or 20weeks (N171-82Q mice). Various behavioral assays were measured over the course of drug treatment whereby GA treatment delayed the onset and reduced the severity of HD behavioral symptoms in both mouse models. The beneficial actions of GA were associated with elevated levels of promoter I- and IV-driven brain-derived neurotrophic factor (Bdnf) expression and reduced levels of cytokines, in particular, interleukins IL4 and IL12, in the brains of HD mice. In addition, the GA-induced effects on BDNF, IL4 and IL12 levels were detected in plasma from drug-treated mice and rats, suggesting utility as a peripheral biomarker of treatment effectiveness. These preclinical studies support the use of GA as a relevant clinical therapy for HD patients.

Use of a highly parallel microfluidic flow cell array to determine therapeutic drug dose response curves.

A high-throughput, microfluidic flow cell array (MFCA) system has been modified to enable drug screening against small-volume cell-, and tissue cultures. The MFCA is composed of a 3D channel network that simultaneously flows fluids through forty-eight 830 µm by 500 µm flow cells, which physically divide and fluidically seal an existing culture into multiple compartments when docked onto the surface of a cell or tissue culture dish. The modified system provides temperature (37 °C) and CO2/pH level controls, while continuously flowing solutions (media or other liquid such as drug suspensions) over the cells/tissues. These assays were enhanced and validated using inverted microscopy and fluorescent staining techniques which also allow real time viability and toxicity assessments. This work presents the results of this new generation in vitro drug testing assay performed using this modified MFCA system. This setup allows the testing of 48 drug combinations on 48 different cell-, tissue specimen at once under flow conditions. All 48 flow cells were utilized to test 5 different concentrations of cisplatin (CDDP). CDDP solutions in various concentrations were continually flowed over cultured human ovarian cancer cells for 48 h. Viability assessments were performed using red-orange calcein and SYTOX ® Green nucleic acid stains. Cells were imaged at the beginning and end of the experiment (48 h). In order to compare and validate MFCAs suitability as drug screening assay, MTT assays were performed on cells. We found that both, MTT and MFCA assays generated dose-response curves with similar profiles. Innovative advantages of the MFCA system include the ability of handling smaller amounts of solutions compared to conventional and current state of the art drug screening and cell viability/toxicity methods. It also provides the ability to continually deliver fresh solution to the cell samples, while eliminating wastes that are produced. Based on our here reported findings MFCA may have a strong potential of providing a more physiological model than current state of the art static MTT assays.

Negative pressure wound therapy combined with acoustic pressure wound therapy for infected post surgery wounds: a case series.

Acute infection of surgical incision sites often requires specialized wound care in preparation for surgical closure. Optimal therapy for preparing such wounds for a secondary closure procedure remains uncertain. The authors report wound outcomes after administering acoustic pressure wound therapy in conjunction with negative pressure wound therapy with reticulated open-cell foam dressing changes to assist with bacteria removal from open, infected surgical-incision sites in preparation for secondary surgical closure in three patients. Before incorporating acoustic pressure wound therapy at the authors' facility, the average negative pressure wound therapy with reticulated open-cell foam dressing course prior to secondary surgical closure was 30 days; with its addition, two of three patients underwent successful surgical closure with no postoperative complications after 21 and 14 days, respectively; one patient succumbed to nonwound-related complications before wound closure. Larger, prospective studies are needed to evaluate combining negative pressure wound therapy with reticulated open-cell foam dressing and acoustic pressure wound therapy for infected, acute post surgery wounds.