bluuebunny/crossref_metadata_2025 huggingface dataset:
NG‐001: A novel multi‐domain digital cognitive intervention for neuropsychiatric symptoms in mild cognitive impairment
Authors: Ng Kok Pin , Patterson Michael D. , Jabar Syaheed Bin , Leonardo Jacklyn , Chiew Hui Jin , Ng Adeline Su Lyn , Kandiah Nagaendran
Published: December 2023

Background

Neuropsychiatric symptoms (NPS) are increasingly recognized as early non‐cognitive manifestations of patients at‐risk of dementia and are associated with accelerated cognitive decline. While cognitive stimulation may be an effective intervention in improving NPS and quality of life of patients and their caregivers, there is a need for a digital intervention that is accessible and scalable so that the benefits of improving behavioral outcomes can be attained on a larger scale. Here, we studied the effectiveness of a novel multi‐domain digital cognitive intervention on NPS among patients with mild cognitive impairment (MCI).

Method

We conducted a pilot 10‐week open‐label clinical trial of 30 MCI patients using the NG‐001, a multi‐domain digital intervention. NG‐001 is a digital program which consists of weekly 1‐hour training in several domains: cognitive games; physical exercise; mindfulness (e.g., yoga and meditation); health literacy; and reminiscence therapy. Participants completed the Depression Anxiety Stress Scale (DASS) and the Mild‐Behavioral Impairment‐Checklist (MBI‐C) at baseline and at the end of the trial. Changes in DASS and MBI‐C scores were assessed using paired Wilcoxon signed ranked tests (two‐tailed) and effect sizes were reported using Hedges’ g.

Result

MCI patients showed significant improvements in depression (4.643 vs. 3.214, g = 0.228), anxiety (6.357 vs. 3.786, g = 0.440) and stress (7.786 vs. 5.429, g = 0.356) scores as measured by DASS with NG‐001 intervention (Figure 1). MCI patients also showed significant improvements in MBI‐C total scores (3.29 vs. 1.43, g = 0.47), the apathy sub‐domain scores (0.96 vs. 0.21, g = 0.54), and the affect sub‐domain scores (1.25 vs. 0.43, g = 0.47) with NG‐001 intervention (Figure 2). Importantly, there was high compliance among the participants who completed the full 10‐week intervention.

Conclusion

A 10‐week multi‐domain digital intervention with NG‐001 reduces the severity of NPS among MCI patients. A longer trial with a control arm is needed to further determine the efficacy of NG‐001 for NPS among MCI patients.
Dementia Associated Disorders, Driving Status and the Relationships between Communication, Anxiety and Objective Cognitive Testing
Authors: Weller Joanna , Kaczmarek Olivia , Gopie Ian , Baek Steven , Bumstead Barbara , Buhse Marijean , Zarif Myassar , Gudesblatt Mark
Published: December 2023

Background

Dementia associated diseases (DAD) refers to a heterogeneous group of disorders that are clinically characterized by progressive cognitive impairment (CI) that ultimately adversely influences an individual’s ability to function independently. CI may reflect abnormalities across multiple cognitive domains to varying degrees and combinations across various cognitive domains (CD). Identifying treatment needs and discussing treatment options requires ongoing communication between patient and provider over the disease continuum; communication capacity may be compromised but underappreciated. Impaired verbal and episodic memory function in people with DAD (PwDAD) can adversely impact communication abilities. Maintaining an effective long‐term treatment plan requires consistent monitoring of both performance ability and patient perspective (patient reported outcomes, PRO) across a continuum of patient needs (health, safety, and QoL).

Method

Retrospective review of information obtained in the course of routine care including driving status, Neuro QOL‐Anxiety Short‐Form (A‐SF); Neuro QOL‐Communication Short‐Form (C‐SF); validated multi‐domain computerized cognitive assessment battery (CAB). CAB Domain Score of Verbal Function (CAB‐V) and Memory Function (CAB‐M). CAB and PRO were completed without provider influence.

Result

530 PwDAD (62% female, average age 71.9 +/‐ 14.3 years) was used to compare patient driving status with A‐SF, C‐SF, NT‐V, NT‐M scores. T‐Tests assuming both equal and unequal variances comparing multiple PRO scores to driving status determined significance at (p<0.01). Statistically significant relationships were identified between driving status and: A‐SF, C‐SF, CAB‐V, and CAB‐M.

Conclusion

Self‐reported anxiety and ability to communicate, objective impairment in verbal, and memory function are related to driving status in PwDAD. Appreciation of disease impact, whether perceived or performance ability, across a continuum should be incorporated in routine care and monitoring of dementia disorders to optimize care and outcome by identifying issues of concern that have both visible and invisible impact both patients and clinicians to design an effective plan of care to accommodate patient centric impairment and needs. Standardized methods of routine PRO collection concerning various aspects of real‐world health outside of a clinic encounter are important to building an effective holistic treatment plan.
Modifiable dementia risk factors associated with distinct subjective and objective cognitive outcomes
Authors: Rosická Anna M , Teckentrup Vanessa , Pringle Andrew , Gallagher Eoghan , Hanlon Anna K , Lawlor Brian , Naci Lorina , Gillan Claire M
Published: December 2023

Background

A range of potentially modifiable environmental, social, and lifestyle factors are estimated to contribute to over a third of dementia cases worldwide. Leading theories propose that these risk factors have different risk‐conferring mechanisms. For example, social isolation, hypertension, and exercise may respectively impact most on cognitive reserve, neurodegeneration, and inflammation. If true, this may support the development of more personalised preventative strategies, depending on risk profiles. Here, we aimed to address this by gathering multiple forms of cognitive assessment in a large sample, across lifespan.

Method

N = 2831 users of a free smartphone app, Neureka (aged 18‐82, M(SD) = 46.84(14.7)), completed questionnaires about their background, health, and lifestyle. Additionally, they completed subjective and objective assessments of their cognitive status, via questionnaires (subjective memory problems, attitude to own ageing, and cognitive fluctuations) and cognitive tests (working memory, processing speed, cognitive flexibility, and model‐based planning), respectively. We tested the differential cognitive correlates of previously established risk factors using univariate regressions, controlling for age and gender.

Result

Lower education and socio‐economic status (SES) were associated with worse cognitive status across all domains (all p<.05). However, the association between SES and subjective cognition (ß = 0.38–0.51) was more than twice that of objective cognition (ß = 0.05–0.09), while this was not the case for education (ß = 0.15–0.32 for subjective and ß = 0.10–0.16 for objective cognition). Subjective measures were also more sensitive to depression, loneliness, hearing handicap, age‐related hearing loss, and tinnitus (all p<.01 for subjective and .001<p<.75 for objective cognition). In contrast, cardiovascular factors like diabetes, hypertension, stroke, and smoking were associated with comparable impacts on objective and subjective cognition. Overall, there was little evidence for risk factor correlates of different aspects of objective cognition (e.g., working memory vs. processing speed).

Conclusion

Objective and subjective cognition have dissociable associations with certain potentially modifiable risk factors for dementia. This may aid in our understanding of the distinct mechanisms through which they confer risk for dementia. The objective cognitive assessments gathered, model‐based planning, memory, processing speed and flexibility, yielded remarkably similar associations with risk factors, suggesting a common mechanism through which they are linked to risk factors for dementia.
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

Background

Chronic 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.

Method

Daily 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.

Result

We 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.

Conclusion

Together, 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

Background

Digital 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.

Method

106 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.

Result

In 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.

Conclusion

Unlike 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

Background

Transcranial 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.

Methods

25 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).

Results

Cognition showed significant improvement in all scores after initial treatment across patients. Mean scores where stable over 12 months. Effects varied between patients.

Discussion / Conclusion

The 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

Background

Despite 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.

Method

This 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).

Result

Primary 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).

Conclusion

BBRT 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

Background

Learning 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.

Method

In 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.

Result

On 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.

Conclusion

VPA‐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

Background

PAL 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.

Method

We 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.

Result

There 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.

Conclusion

This 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

Background

Persons 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.

Method

CPs (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.

Result

A 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.

Conclusion

High 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

Background

Social 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.

Method

Intervention 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.

Result

As 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.

Conclusion

Previously 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

Background

In 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.

Method

The 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.

Result

Caregivers, 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.

Conclusion

The 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

Background

Financial 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.

Method

18 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.

Result

All 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.

Conclusion

Results 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.
Further Validation of a Self‐administered Smartphone‐based Verbal Learning and Memory Assessment
Authors: Edgar Chris J. , Cummins Hannah , Bransby Lisa , Bird Laura J. , Fredrickson Amy , Maruff Paul , Lim Yen Ying
Published: December 2023

Background

The International Shopping List test (ISLT) is a verbal word list learning test set within a realistic shopping list context, supporting ease of cultural adaptation, and addressing content validity and patient relevance. Improvements to and the wide adoption of natural language processing (NLP) software has enabled the possibility for self‐administered tests of verbal learning. LilaTM a self‐administered, smartphone‐application (app) was developed, using the virtual assistant and NLP. We have previously reported acceptability and usability data from qualitative analysis of concept elicitation interviews. We now seek to provide preliminary validation data around its use.

Method

A convenience sample of healthy young adults (n = 40), M(SD)age = 35 (16), were invited to install and complete one assessment of the LilaTM app. A usability survey was also administered to explore participants’ experiences. The sample was predominantly female (70%) and of Asian ethnicity (62.5%). Data were collected in Australia, using an English word pool developed for the USA.

Result

Acceptability was generally high with N = 38 completing immediate recall rounds and N = 32 completing the delayed recall round. Eight‐two percent found it extremely or somewhat easy to hear and understand what items were on the shopping list and 95% indicated that it was extremely or somewhat easy to understand what they had to do to complete the assessment. Scoring accuracy was 88% at the word item level, with reprocessing to address accent, context setting, and other NLP approaches to improve accuracy underway e.g., homophones biased to the grocery item.

Conclusion

Whilst acceptability was high, the importance of localization of test stimuli was confirmed as well as the need for additional data processing options to account for accent. Continued optimization of data processing to score participant responses and word item pools to reduce ambiguity is expected to further improve accuracy e.g., accounting for regional accents and consideration of homophones and compound words. However, specific characteristics of speech including in those for whom English may be a second/foreign language will be an area of focus for future development.
Humanoid Robots administering Cognitive Stimulation Therapy to help improve cognition and reduce neuropsychiatric disorders
Authors: Khan Arshia A
Published: December 2023

Background

Dementia is a progressive disease that causes a continuous decline in cognition. People affected with dementia are also at high risk for neuropsychiatric disorders requiring frequent therapy sessions. The current healthcare worker shortages have made finding a therapist challenging, resulting in increased hospital admissions due to an increase in neuropsychiatric disorders in people affected with dementia. To address this problem humanoid robots and wearable sensors were programmed to administer Cognitive Stimulation Therapy(CST), a therapy that doesn’t require a clinician to be administered. CST is an evidence based therapy that is administered twice a week for seven weeks. The wearable sensors track and monitor the physiological data and are able to predict neuropsychiatric symptoms. The robots interact, communicate and administer the therapy while the participants are wearing the sensors along with artificial intelligence algorithms that track the physiological data to help predict any neuropsychiatric symptoms.

Method

A humanoid robot, Pepper was programmed to administer Cognitive Stimulation Therapy to be deployed in nursing homes to help improve cognition and also help alleviate neuropsychiatric symptoms. The protocol involves conducting a cognitive assessment using the MMSE prior to initiation of the Cognitive Stimulation Therapy. The Cognitive Stimulation Therapy is administered twice a week for seven weeks. At the end of the fourteen sessions the MMSE is administered again to measure the cognition levels. Additionally pre and post surveys for depression, quality of life, Pittsburgh sleep index/ sleep quality and activities of daily living are conducted to monitor the neuropsychiatric symptoms. During the entire seven weeks the participants physiological data is tracked and analyzed using artificial intelligence algorithms to predict neuropsychiatric symptoms. The combination of the humanoid robots and the wearable sensors work in sync to improve cognition and reduce behavioral and psychological symptoms of dementia..

Result

The robot is successfully programmed and tested in the lab setting. The study is successfully designed.

Conclusion

Robots can be employed to administer cognitive stimulation therapy to help improve cognition and reduce neuropsychiatric symptoms in people affected with dementia. Robots have the potential to address healthcare worker shortages.
Machine Learning Approach to Identify Dysregulation in the Plasma Proteome of CADASIL
Authors: Keller Jonah , Fitzsimons Stephen , Park Ryan , Moury Luana , Oh Bradley C , Treiman Scott , Radabaugh Hannah , Ferguson Adam , Elahi Fanny M
Published: December 2023

Background

The plasma proteome provides information to identify dysregulated molecular pathways underlying disease. Cerebrovascular diseases often manifest a significantly different plasma proteomic signature. Cerebral‐Autosomal‐Dominant‐Arteriopathy‐Subcortical‐Infarcts‐and‐Leukoencephalopathy (CADASIL) is one such vascular brain disease. The CADASIL plasma proteome has yet to be investigated.

Method

To investigate the plasma proteome in the context of CADASIL, we used large‐scale proteomics, measuring over 7,000 proteins via aptamer‐based technology (SomaLogic) from 53 study participants (nCADASIL = 25; nControl = 28). We employed machine learning (ML) methods as an unbiased approach to uncover disease‐associated change in proteomic networks. This approach is based on the premise that protein sets that best classify disease state could be important biological drivers of disease. We developed a novel ML method: coupling recursive feature extraction with logistic regression (LR) and XGBoost evaluators, as well maximum‐relevance‐minimum‐redundancy with Random‐Forest and F‐Statistic evaluators. The results of all four models were selectively aggregated in order to delineate the CADASIL plasma proteome signature while minimizing overfitting to the low sample size data. We developed a 45 protein model of the CADASIL proteomic signature from these results. To evaluate the classification ability, we tested the Repeated‐Stratified‐10‐fold‐Cross‐Validation accuracy of a LR classifier. Next, we investigated whether the CADASIL proteomic signature was relevant for other neurodegenerative diseases with vascular components; the classifier was applied to an Alzheimer’s Disease (AD) dataset. Finally, the functional signature of the 45 proteins was investigated through gene ontology (GO).

Result

The LR classifier in CADASIL is 99.8% accurate. In AD, the accuracy is 71.2%. This implies the CADASIL signature shares commonalities as well as pertinent differences with other neurodegenerative diseases. The GO of the 45 proteins resulted in GO terms corresponding to extracellular matrix and collagen, cellular membrane lipoproteins and glycolipids, and proteasome biological pathways.

Conclusion

The proposed method allows for an initial unbiased discovery of important proteomic changes associated with disease state. The identified proteins would provide starting points for mechanistic studies. In addition, a panel of proteins could be used for screening at population level for risk stratification and more in‐depth phenotyping. Next steps include investigating the biological relevance of findings in mechanistic models for therapeutic developments.
Monitoring Daytime Napping in Community Dwelling Older Adults Using Contactless Sleep Technologies
Authors: Ravindran Kiran K.G. , Monica Ciro Della , Atzori Giuseppe , Lambert Damion , Revell Victoria Louise , Dijk Derk‐Jan
Published: December 2023

Background

Increased daytime napping and excessive sleepiness are associated with cognitive decline in older adults, especially in people living with dementia (PLWD) [1]. Subjective assessments of naps are burdensome and maybe unreliable in PLWD and hence there is a need for technologies that provide objective longitudinal assessment of the incidence and duration of naps. Here we compare two contactless sleep technologies (CSTs) against sleep diary and actigraphy for monitoring daytime napping in community dwelling non‐demented older adults.

Method

Two under‐mattress CSTs (Withings Sleep Analyser [WSA] and Emfit QS [Emfit]) along with actigraphy (Actiwatch Spectrum [AWS]) were deployed in the home of 17 older adults for a period of 14 days ( = 65 years; Mean Age ± SD = 72 ± 4.49; 6 Women). The ground truth nap information was collected using an extended consensus sleep diary that included additional information about naps (timing, duration, and location). We analyzed the agreement of the napping events and duration estimated by WSA, Emfit and AWS against the sleep diary reported events.

Result

The CSTs only detected in‐bed naps whilst the AWS detected both in‐bed and not‐in‐bed naps. Although all the compared devices detected spurious naps unreported in the sleep diary, it was highest in AWS (81% of total naps detected) followed by Emfit (63%) and WSA (16%) as shown in Figure 1. Among the CSTs, WSA accurately detected more in bed naps while registering less spurious naps compared to Emfit but had lower duration agreement to sleep diary (Figure 2). Further, when the contribution of daytime naps to 24‐h total sleep time was computed, the WSA estimate (12.8±6.1%) was closest to the sleep diary estimate (12.9±9.1%) followed by AWS (15.6±9.9%) and Emfit (17.2±11.1%).

Conclusion

CSTs, with their ability to provide both contextual location information and objective measures of napping, such as timing and duration, offer a reliable and unobtrusive alternative to traditional methods such as sleep diary and actigraphy for long‐term round‐the‐clock monitoring of sleep in older adults. References: [1] Li, P, Gao, L, Yu, L, et al. Daytime napping, and Alzheimer’s dementia: A potential bidirectional relationship. Alzheimer’s Dement. 2023; 19: 158– 168. https://doi.org/10.1002/alz.12636
Rapid, scalable assay of amylin‐β amyloid co‐aggregation in brain tissue and blood
Authors: Kotiya Deepak , Leibold Noah S , Verma Nirmal , Jicha Gregory , Goldstein Larry B , Despa Florin
Published: December 2023

Background

Islet amyloid polypeptide (amylin) secreted from the pancreas crosses the blood brain barrier into the brain parenchyma and interacts with Alzheimer’s disease (AD) associated cerebral ß‐amyloid (Aß) plaques, which are found in both sporadic and early‐onset familial AD. Immunoprecipitated amylin from human AD brain tissue analyzed by Western blot using an anti‐Aß antibody detects Aß immunoreactivity, which indicates that the amylin and Aß peptides aggregate in the brains of humans with AD, forming amylin‐Aß hetero‐oligomers that are sodium dodecyl sulfate (SDS)‐soluble. We report the development of an ELISA to detect amylin‐Aß hetero‐oligomers in brain tissue and blood.

Method

The amylin‐Aß ELISA relies on a monoclonal anti‐Aß middomain antibody (detection) and a polyclonal anti‐amylin antibody (capture) designed to recognize an epitope that is distinct from the high affinity amylin‐Aß binding sites. We screened temporal cortex homogenates obtained from 13 cognitively unaffected (CU) humans and 47 persons with sporadic AD (sAD) for amylin‐Aß hetero‐oligomers. Individuals were of similar age (sAD, 85.65 ± 7.04 years vs. CU, 87.22 ± 7.30 years; p = 0.482). Brain tissue amylin and Aß concentrations were measured using conventional ELISAs. Amylin‐Aß oligomer levels were also measured in whole blood lysates from APP/PS1 rats and APP/PS1 rats expressing amyloid forming amylin in the pancreas (APP/PS1/HIP rats; all rats age‐matched, 16‐months).

Result

The brains of most AD patients had detectable amylin‐Aß hetero‐oligomer concentrations, whereas about half of those CU had brain tissue amylin‐Aß hetero‐oligomers below the detection limit (0.02 ng/mg total protein; one‐way ANOVA, P < 0.0001). Amylin‐Aß hetero‐oligomers were more common in brains with frequent neuritic plaques (CERAD C). Higher brain tissue amylin‐Aß hetero‐oligomer levels were associated with greater brain tissue amylin concentrations (r = 0.38; P < 0.05). There was no correlation between cerebral amylin‐Aß hetero‐oligomer accumulation and age in the analysis of samples from sAD and CU groups (r = ‐0.22; P > 0.05). Levels of amylin‐Aß hetero‐oligomers in whole blood lysates obtained from APP/PS1/HIP rats were higher than those from APP/PS1 littermates (P < 0.05).

Conclusion

Studies are needed to determine the extent to which amylin‐Aß hetero‐oligomerization can be detected in human blood.
Tele‐Dementia in Africa: Setting roadmap for implementation
Authors: Farombi Temitope Hannah , Akinyemi Rufus O. , Ogunniyi Adesola
Published: December 2023

Background

Alzheimer’s disease and dementia related disorder incidence and prevalence continue to increase in Africa due to changing ageing demographics. Despite this rise, overall quality and quantity of available evidence to inform best practices in recruitment, retention and inclusion of underrepresented population in ADRD research is very low. Africa needs creative innovations to bridge the dementia care gap and telemedicine offers a unique opportunity for prompt diagnosis, follow up and care support

Method

This was an observational study of remote video assessment of persons living with Dementia and their caregivers. Mobile phone and web‐based applications for virtual consultation and health information management system were built to engage patients with various clinical conditions across multiple specialties. The assessment and follow up were done between September 2020 and December 2022.Cognitive assessment tools were administered via telemedicine platform for screening and post diagnostic management due to the COVID‐19 lock down

Result

A total of 50 patients with Dementia and their caregivers attending Neurology clinic at the Geriatric centre UCH were engaged on the platform for clinical follow up. Mean(+SD) age of was 74.0(+7.2) year and 56% were females, 82.8% had some form of formal education, 67.2% married and 97.9 lived with other persons. Over 31.9% participants had at least one comorbidity. 93% of the participants expressed satisfaction with video conferencing platform. 87% retention rate on follow up on the platform,13% of drop out rate due to technical fault and poor internet connection

Conclusion

we believe implementation of telemedicine will improve recruitment and retention of persons living with dementia and it offers a promising dementia management strategy for Africa