bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non‐invasive Flicker Neurostimulation Boosts Resilience to Psychological Stress
Authors: Franklin Tina C , Goodson Matthew , Gajelli Tarini , Rutledge Catherine , Tharayil Jacob , Pennebaker Sarah , Naik Arya , Singer Annabelle C 
Published: December 2023

AbstractBackgroundChronic stress promotes life‐long risk for neuropsychiatric decline by increasing neuroinflammation and disrupting synaptic health and plasticity. Our lab and others have recently demonstrated that non‐invasive gamma sensory flicker stimulation modulates inflammatory signaling, restores microglia function and improves cognitive performance in mice models of Alzheimer’s disease (AD). However, no research to date has studied the effects of flicker in the context of stress. Accordingly, our goal for this study was to determine how sensory flicker stimulation mitigates neuropsychiatric‐like behavioral deficits and rescue glia and synapse pathology following chronic stress.MethodDaily flicker intervention was introduced concomitantly with daily stress exposure (28 days) at multiple frequencies in male and female C57BL6 and Thy1‐GFP mice (n = 6/group per sex). The mice were then tested for anxiety‐like and anhedonia using a range of behavioral tests. Next, we quantified spine density changes in Thy1‐GFP mice and quantified GFAP‐labeled astrocyte morphology change, a reliable proxy for astrocyte reactivity, in the medial PFC using the semi‐automated Imaris imaging software to determine synaptic health and inflammatory profile, respectively.ResultWe show for the first time that stress‐induced morphological changes in the medial PFC are modulated in a sex‐, and frequency‐specific manner that coincides with behavioral resilience in stressed mice. Our findings indicates that audio‐visual flicker protect against stress‐induced behavioral deficits (p<0.0001) and improves neuroinflammation (p<0.01) in a sex‐ and frequency‐specific manner.ConclusionTogether, these findings show frequency tunable flicker intervention improves stress pathology and may prevent neuropsychiatric health decline in conditions with sex dimorphic symptoms and prevalence.
Classifying Memory Clinic Patients Using the Digital Clock Drawing TestTM, Mini‐Mental State Examination, and Philadelphia (repeatable) Verbal Learning Test
Authors: Libon David J , Swenson Rodney , Jannati Ali , Bates David , Tobyne Sean , Pascual‐Leone Alvaro , Gomes‐Osman Joyce Rios 
Published: December 2023

AbstractBackgroundDigital cognitive assessments (DCA) enable quick, sensitive, and reliable assessment of neurocognitive operations that underlie dementia and mild cognitive impairment (MCI). We examined how well the DCTclockTM DCA, Mini‐Mental State Examination (MMSE), and Philadelphia (repeatable) Veral Learning Test (PrVLT) can classify memory clinic patients by cognitive impairment profile.Method106 serial referrals to an outpatient memory clinic were assessed with the DCTclock, MMSE, and P(r)VLT. Using statistical criteria for subtle cognitive impairment (SCI, Edmonds et al., 2015) and MCI (Jak et al., 2008), patients were classified into cognitively normal (CN, n = 21), SCI (n = 33), amnestic MCI (aMCI, n = 22), and dysexecutive/mixed MCI (d/mMCI, n = 30) groups. A series of stepwise logistic regression analyses were conducted with CN participants as the criterion group.ResultIn the first analysis (Table 1), P(r)VLT‐recognition (X2 = 24.39, p<0.001) entered the model first followed by the DCTclock Score (X2 = 16.68, p<0.001). P(r)VLT‐recognition classified aMCI patients (Wald = 11.21, p<0.001). DCTclock (Wald = 8.97, p<0.001) and P(r)VLT‐recognition (Wald = 4.06, p<0.001) classified d/mMCI patients. In the second analysis the four command DCTclock composites were analyzed, excluding the MMSE and P(r)VLT‐recognition scores, Spatial Reasoning classified patients into their respective groups (SCI, Wald = 3.68, p<0.055; aMCI, Wald = 8.84, p<0.003; d/mMCI, Wald = 19.12 p<0.001). Third, analyzing DCTclock command Spatial Reasoning, MMSE, and P(r)VLT‐recognition, the P(r)VLT score, again, entered first (X2 = 24.39, p<0.001) followed by DCTclock Spatial Reasoning (X2 = 18.95, p<0.001). DCTclock Spatial Reasoning classified SCI patients (Wald = 4.66, p<0.031), P(r)VLT‐recognition classified aMCI patients (Wald = 9.11, p<0.003), and both DCTclock command Spatial Reasoning (Wald = 10.56, p<0.001) and P(r)VLT‐recognition (Wald = 3.32, p<.068) classified d/mMCI patients.ConclusionUnlike the MMSE that takes 10‐15 minutes to administer and is scored subjectively, all DCTclock data are digitally obtained and automatically scored, requiring no examiner interface for administration and interpretation, thus obviating clinical judgment, ensuring inter‐rater reliability, and enabling more efficient cognitive assessments. In this series of logistic regression analyses, a combination of DCTclock and P(r)VLT clearly outperformed the MMSE in classifying non‐demented memory clinic patients into cognitively normal, subtle cognitive impairment, and MCI subtypes. These results support the efficacy of DCAs in clinical trials and to screen for emergent cognitive impairment in primary care and specialty medical practices.
Transcranial Pulse Stimulation (TPS) in Alzheimer´s: Long term retrospective group data and individual patient histories
Authors: Wojtecki Lars 
Published: December 2023

AbstractBackgroundTranscranial Pulse Stimulation (TPS) uses shockwaves for the treatment of Alzheimer´s Disease (AD). Our group published short term results after the first treatment cycle (Cont et al. 2022). Long term data has not been reported yet.Methods25 TPS‐treated patients were examined. All patients received 4Hz TPS of about 6000 pulses of 0.2 mJ/mm2 (navigated bifrontally, biparietally, bitemporally and praecuneus) using the Neurolith System (Storz Medical). After the initial treatment cycle over 2 weeks patients receive monthly booster sessions. Cognitive scores (ADAS, MMST, MoCA) are available up to 6 (n = 10) and 12 months (n = 5).ResultsCognition showed significant improvement in all scores after initial treatment across patients. Mean scores where stable over 12 months. Effects varied between patients.Discussion / ConclusionThe initial improvement of cognitive functions can be maintained up to 12 months in this retrospective. Prospective controlled trials need to done as next step.
Clinical efficacy of Brain and Body Rehab Training (BBRT) multi‐dimensional cognitive intervention digital therapeutic in patients with mild cognitive impairment: a three‐arm, randomized controlled trial
Authors: Li Yatian , Wu Jingnan , Wang Ziming , Xia Huanhuan 
Published: December 2023

AbstractBackgroundDespite lacking effective pharmacological therapeutic to delay the progression of mild cognitive impairment (MCI) to dementia, accumulative evidence showed that multi‐domain intervention including cognitive training, exercise, diet, etc., is an effective approach. With miscellaneous audio and visual stimuli, emerging digital therapeutic can be incorporated into the multi‐domain intervention and enhance the effect of cognitive interventions. This study adopted the Brain and Body Rehab Training (BBRT) multi‐dimensional cognitive intervention system to develop the BBRT‐online digital therapeutic (BBRT‐online, Figure 1) and will verify the efficacy of both BBRT and BBRT‐online on older patients with MCI.MethodThis study is a 2‐year, three‐arm, randomized controlled trial, intended to recruit 438 patients with MCI aged 50‐75, with 6 years of education or more, and no neurological disorders or other serious systemic diseases. The participants will be randomly assigned into the BBRT‐online intervention group (n = 200), BBRT intervention group (n = 38), or control group (n = 200). The control group will receive regular health education as the other two groups. Five BBRT‐online training units a day, 15 minutes at least, will execute remotely in the BBRT‐online group. Participants in the BBRT group will attend face‐to‐face BBRT cognitive training twice a week, 1 hour for each at least. Both intervention groups will receive intervention for 12 months and be followed up until the 24th month to assess the persistence of efficacy (Figure 2).ResultPrimary outcome of this study will be the ACE‐III total score. Secondary outcomes will include 1) neuropsychological scale scores including the MOCA‐B scale, NPI scale, AVLT scale, STT scale, BNT test, and SCS intelligent voice‐based cognitive assessment. 2) Biomarker outcomes: Aß42, T‐tau, and P‐tau. 3) Neuroimaging outcomes. All participants will meet the research nurse at baseline, and at 6, 12, 18, and 24 months for outcome measurements. This study has been registered in the China Clinical Trials Registry (ChiCTR2200065212).ConclusionBBRT and BBRT‐online have been widely commercialized. This study will systematically evaluate the clinical effectiveness of both BBRT and BBRT‐online for Chinese MCI patients and provide insights into non‐pharmacological intervention mechanisms for improving cognitive function.
Feasibility of Remote Automated Verbal Paired Associate (VPA) Learning Over Repeated Exposure (LORE)
Authors: Kaula Alexander J , Cormack Francesca K , Taptiklis Nick 
Published: December 2023

AbstractBackgroundLearning over repeated exposure (LORE) in periods of days or months has been shown in recent studies to be sensitive to amyloid load where short‐term learning tested in immediate recall was not (Samaroo et al., 2020). Prior LORE studies have used visual presentations of words, non‐words, and faces. We addressed the feasibility of using validated verbal paired associate (VPA) stimuli in an automated LORE task, with verbal delivery and scoring performed by our NeuroVocalix system using text‐to‐speech (TTS) and automated speech recognition (ASR). Previously we have shown that using a word‐pair memorability model based on natural language characteristics to generate sets of VPA word‐pairs of equivalent memorability allows for repeated testing with interchangeable stimulus sets. Here we explore the use of one such set in an adaptation of VPA that assesses LORE rather than immediate recall and shows promising results.MethodIn this pilot study, we assessed memory performance in 20 older adults (10m, 10f) aged 65+ years, (M = 70.7, SD = 4.65), recruited using the Prolific online platform with the test delivered using our proprietary system. The task for participants was to learn a set of eight word‐pair associations over a burst of five days. On the first day, participants heard the word‐pair set, and were immediately tested for recall of that set. On days two, three, and four of the study, participants first attempted cued recall of the eight word‐pairs, after which the set was presented again, and the session ended. On the final day, cued recall was tested for the last time.ResultOn the first day, immediate recall scores were in line with first attempt VPA scores observed in validation work. On the second day of the series, scores fell through forgetting, and then learning over three further exposures showed monotonically increasing recall scores with neither ceiling nor floor effects across the group. Adherence was excellent, with 99% of sessions successfully completed, and participants reported high enjoyment of the task and eager anticipation of sessions.ConclusionVPA‐form LORE using our validated VPA word‐pair stimuli performs well and shows promising task characteristics in a representative sample.
Exploring the Behaviour, Reliability, and Usability of a new Smartphone Version of Paired Associates Learning
Authors: Kaula Alexander J , Taptiklis Nick , Cormack Francesca K 
Published: December 2023

AbstractBackgroundPAL is a well‐known and trusted task with good sensitivity to deficiencies in memory capabilities. There has been considerable interest in a smartphone version of PAL, and Cambridge Cognition has now completed work on smartphone PAL. Parallel work has shown that this new version of PAL is of equivalent difficulty to the existing classic PAL, and this study addresses characteristics of the smartphone version alone, in a well‐powered within‐subjects study designed to assess test‐retest reliability, bias, and the usefulness of a familiarisation session, as well as exploring usability.MethodWe obtained three PAL scores over three consecutive days in 86 (31 m, 55 f) participants aged 55+ (M = 57.6, SD = 5.65) via the Prolific online platform. Each day participants used their own devices to complete the smartphone PAL task. We analysed adjusted error scores up to eight‐box problems, with participants showing extreme score fluctuations (M +/‐ 3xSD) excluded on the basis that the task was not taken under comparable conditions. We analysed test‐retest reliability using Pearson correlations of scores over the three days and analysed the effect of a familiarisation session by looking at mean scores over three days.ResultThere was some attrition of users due to technical issues in the prototype version of the task, but adherence was good, and participants reported high levels of task enjoyment and satisfaction. Test‐retest reliability between familiarisation and Day Two was good, r = .63, and very good between Day Two and Day Three, r = .7. Analysis of mean scores showed that the familiarisation session had a significant effect, with task learning between familiarisation and Day Two significantly greater than between Day Two and Day Three. Participants reported good enjoyment of the task, and overwhelmingly described usability characteristics in positive terms.ConclusionThis study highlights the value of a familiarisation session in reducing learning effects, and, like classic PAL, shows good to very good reliability. Moreover, PAL on a smartphone was well‐liked by these older participants, supporting its use in older populations.
Care partner burden and emergency service use: what is the link?
Authors: Lindauer Allison , Gothard Sarah , Bernard Hannah , Steele Joel S. 
Published: December 2023

AbstractBackgroundPersons with dementia (PWD) are significantly more likely to use emergency services (defined here as emergency department or urgent care visits) than age‐matched controls (1). The bi‐directional relationship between care partner (CP) burden and their PWD’s emergency service use is not well‐understood (2). A possible limiting factor is the infrequent assessment of emergency service use by the PWD and corresponding CP burden. Here, we used high frequency longitudinal data from the telehealth‐based Tele‐STELLA (Support via TEchnology: Living and Learning with Advancing ADRD) study (NIA R01AG067546) to examine the relationship between CP burden and PWD emergency service use.MethodCPs (n = 80; age = 65.7±11.6 years) completed weekly online “Orbit” surveys (3). The survey measures burden (ZBI‐4 [9±3.48 points]), cost‐of‐care, medication use, and emergency service use (4). Using R software (5), descriptive statistics and generalized mixed effect models were developed to examine the effects of CP burden on PWD emergency service use.ResultA median of 27 (min = 1;max = 61) weeks of CP responses were captured. Simple generalized mixed effects models showed a significant positive relationship between ZBI‐4 scores and emergency service use the week of event occurrence (ß = 0.0853; p = 0.04). As ZBI‐4 scores increased, the greater the likelihood of an event. Additionally, a mixed effects model that examined the 5 weeks prior to emergency service use showed the absolute magnitude of change of ZBI‐4 scores had a negative relationship to the events (ß = ‐0.393;p = 0.00;OR = 0.675). Taking the results of the two models together, as the range of burden narrowed towards higher ZBI‐4 scores, the chance of emergency service use increased.ConclusionHigh frequency electronic self‐reported data in this telehealth‐based study allowed for identification of emergent events closer to real time than the standard practice. As the range of CP burden scores decreased, trending toward higher burden, there was an increased likelihood of emergency service use occurring for the PWD. This information can be used to anticipate the likelihood of future events and create targeted interventions both for the CP and PWD prior to the need of emergency service use. Limitations in this analysis and gaps in research on this topic warrant further investigation.
I‐CONECT Intervention Effects on Weekly Time Spent Outside of Home and Social Contacts among Socially Isolated Older Adults with Normal Cognition and Mild Cognitive Impairment
Authors: Yu Kexin , Wu Chao‐Yi , Silbert Lisa C , Kaye Jeffrey A , Dodge Hiroko H 
Published: December 2023

AbstractBackgroundSocial isolation has been linked to an increased risk of cognitive decline and incident dementia. Socially isolated individuals tend to lack access to cognitively stimulating activities. This may adversely impact their cognitive health. The Internet‐Based Conversational Engagement Clinical Trial (I‐CONECT) was designed to deliver online conversation sessions to socially isolated older adults to slow cognitive decline and ultimately delay the onset of dementia. The current study examined the intervention effects on participants’ weekly time spent out‐of‐home and their social interaction with family and friends as clinically meaningful functional outcomes.MethodIntervention group engaged in 30‐minutes video chat 4 times/week and 10‐minute weekly phone calls, while control group received only 10‐minute weekly phone calls over 48 weeks. In each call, we asked participants to report time spent out‐of‐home and whether they contacted family or friends during the week (yes/no). Linear mixed‐effect models were run for time spent out‐of‐home, and mixed‐effect models with a logistic link were performed for contact with family and friends. The intervention effect was modeled by including an interaction term of time (in weeks) and group assignments. We ran analyses separately for participants with normal cognition (NC) and mild cognitive impairments (MCI). All models controlled for age, sex, race, education, and a pre vs. post COVID‐19 pandemic indicator.ResultAs weeks passed, participants (N = 155, mean age 81, 72.3% female, 17.53% African American, 51.95% MCI) in both groups reported spending more time out of home, indicated by a significant time main effect (B = , p<.001). Among NC participants, the intervention group had a steeper increase in their reported time spent out‐of‐home compared to the control group (B = , p = .016). Among MCI participants, the intervention group had an increased likelihood of contacting friends over time (OR = 1.013, p = .001), while the intervention effect on contact with family was not significant for either the NC or MCI group.ConclusionPreviously we reported the I‐CONECT intervention positively affected cognitive functions. The current results suggest the translational effects of I‐CONECT to functional outcomes beyond cognitive test scores, activating weekly activities among socially isolated older adults. The intervention provides a remote social interaction platform that brings cognitive stimulation to at‐risk populations.
Scaling Digital Biomarker Discovery with the Cloud and Wearable Devices
Authors: Ford Colby T , Corkey Jon 
Published: December 2023

AbstractBackgroundIn clinical trials and other disease research, biomarkers provide a valuable indication of drug performance and disease progression. Traditionally, these biomarkers may include genomic factors, lab test results, and more, but we now can easily expand into longitudinally collected digital biomarkers from consumer smart devices.MethodThe Amissa platform, built on the Microsoft Azure cloud, enables the collection of high frequency data from consumer smartwatches (such as the Apple Watch and Samsung Galaxy watch devices). The API‐driven cloud architecture enables secure sensor data collection including location, gyrometry/accelerometry, activity monitoring/pedometry, and biosensors such as oxygen saturation and heart rate. This solution allows for sub‐minute capture frequency while balancing device battery drain. The ISO 27001:2013‐compliant platform is globally scalable through an innovative cloud‐native design that ensures security and compliance.ResultCaregivers, researchers, and healthcare providers can now monitor loved ones/patients through consumer‐grade wearables, providing a cost‐effective, accurate, and flexible solution for biomarker discovery, data collection, and remote monitoring.ConclusionThe Amissa platform successfully enables digital biomarker development and helps to address disparities in clinical trials and research studies of underrepresented groups through decentralized data collection. Plus, the platform address security and privacy considerations while enables collaborative research participation and flexible study designs. Note: In this presentation, we will discuss the NIH‐funded work of Amissa and the cloud‐first approach taken to build the world’s first global‐scale platform for disease research using wearable devices. We will cover technical design patterns, considerations for privacy and security, the effect of decentralized data collection on addressing health disparities and inclusion in clinical trials, and the future of digital biomarker discovery in Alzheimer’s disease and related dementias.
Easy‐to‐use personalized legal and financial planning tool for AD/ADRD caregivers and persons with dementia
Authors: Lunde Angela M. , Forsberg Leah K. , Seifert Sara J. , Kramer Kevin M. , Knutson Matthew , Rethemeier Nicholas , Fields Julie A. 
Published: December 2023

AbstractBackgroundFinancial management is one of the most cited sources of stress among caregivers. Legal planning presents additional challenges. Only a small percentage of dementia caregivers report successfully completing necessary planning. Further, persons with dementia are vulnerable to fraud, scam, and inappropriate financial transactions. With stakeholder participation, we explored a novel solution using state‐of‐the‐art technology aimed to overcome impediments that have plagued prior legal and financial planning resources.Method18 stakeholders from 10 organizations across the U.S. serving persons with dementia and caregivers participated in two 60 to 90‐minute semi‐structured interviews that were recorded and transcribed. Qualitative stakeholder input was collected through an iterative process. During initial interviews, a mockup was shared to elicit feedback. There was a 3‐month wait after the first interviews to incorporate recommendations into the evolving prototype. During the second round of interviews, stakeholders evaluated the prototype progress based on feedback they previously provided. Stakeholders then completed an electronic survey to assess their overall confidence in the value of the future tool. A phase 1 prototype was designed using Adobe XD. Stakeholders influenced the content, layout, colors, and images with goals of clarity, usability, legibility, and simplicity. Included are a ‘how the tool works’ section; a wizard that guides users through a topic by asking questions, responding appropriately, a prioritized to‐do list; a chatbot; and a dashboard for viewing progress and sharing with selected care partners. Responses to questions were generated by legal and financial experts.ResultAll 18 stakeholders confirmed that financial management and legal planning are highly stressful for persons with dementia and their families and that there is a need for a tool of this type. 85% of the stakeholders indicated that were extremely satisfied, or very satisfied that the tool would be a beneficial product.ConclusionResults confirmed the need for and utility of an easy‐to‐use tool assisting in legal and financial planning. Phase 2 will incorporate additional content and features along with further review from legal and financial experts. Persons living with dementia and care partners will be included in the testing, evaluation, and further refinement of the technology tool.