bluuebunny/crossref_metadata_2025 huggingface dataset:
The structural integrity of anterior‐temporal and posterior‐medial brain regions in Alzheimer’s disease and Parkinson’s disease: Effects of APOEε4, p‐tau181 and Aβ42
Authors: Coughlan Gillian T , Zhukovsky Peter , Sanchez Erlan , McLaughlin Paula , Grady Cheryl , Black Sandra E. , Munoz Douglas , Buckley Rachel F. , Masellis Mario
Published: December 2023

Background

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two distinct neurodegenerative brain conditions associated with varying degrees of cognitive impairment, including an overlapping amnestic phenotype. At autopsy, APOEe4 and AD proteinopathies are associated with dementia severity in both AD and PD. The extent to which in‐vivo AD biomarkers are associated with memory and underlying regional brain volume in AD and PD patients is under‐investigation. Here, we focused on plasma biomarker associations with anterior‐temporal and posterior‐medial regions that are known to accumulate tau and Aß in AD.

Method

Neuroimaging, biomarker, genetic and cognitive data were collected from 244 patients through the Ontario Neurodegenerative Disease Research Initiative (MeanAge = 68.96; 41% women; 35%APOE‐e4‐carriers). Based on clinical diagnostic criteria, three groups were formed: i)AD with mild cognitive impairment or dementia(ADMCI/ADD;N = 120), ii)PD with MCI or dementia(PDMCI/PDD;N = 76) and iii)PD with normal cognition(PD‐NC;N = 48). Linear regressions assessed clinical diagnosis differences in the volumetric integrity of a priori regions: anterior‐temporal(ATN; including amygdala, fusiform gyrus, and ITG) and posterior‐medial(PMN; including PCC, parahippocampal cortex and precuneus;Fig1). Differences on related item recognition memory and associative memory was examined via the FaceName Association Task. APOE(e4‐/e4+), p‐tau181‐UGOT and Aß42 associations between ATN/PMN and item recognition/associative memory outcomes were estimated. Diagnostic*APOEe4*ptau181 interactions were tested. Age, sex, education and ICV were covaried.

Result

Background characteristics showed that the ADMCI/ADD group exhibited the oldest age and the highest frequency of female sex and e4‐carriership. ADMCI/ADD and PDMCI/PDD, but not PD‐NC, exhibited elevated ptau181 and Aß42 relative to a healthy control group. Both ADMCI/ADD and PDMCI/PDD groups exhibited PMN and ATN degradation, as well as memory impairment, relative to the PD‐NC(Fig2A‐B). Plasma p‐tau181 was associated with ATN and PMN, as well as associative memory(Fig3A). APOEe4 was associated with PMN only, as well as item recognition(Fig3B). Diagnostic*APOEe4*ptau181 interactions were not significant. Post‐hoc analysis showed significant p‐tau181xAPOEe4 interactions on item recognition and total white matter hyperintensity(WMH;Fig3C). Aß42 was not associated with outcomes.

Conclusion

Volumes of the ATN and PMN are lower in cognitively impaired AD and PD patients with higher p‐tau and/or APOEe4‐carriership. P‐tau and APOEe4 may work synergistically to promote domain‐specific memory impairment and WMH burden in both AD and PD.
Association of reactive astrogliosis and microglial activation with tau pathology in Alzheimer’s disease
Authors: Ferrari‐Souza João Pedro , Bellaver Bruna , Ferreira Pamela C.L. , Povala Guilherme , Lussier Firoza Z , Leffa Douglas Teixeira , Therriault Joseph , Tissot Cécile , Benedet Andrea Lessa , Soares Carolina , Aguzzoli Cristiano Schaffer , Zalzale Hussein , Rohden Francieli , Wang Yi‐Ting , Chamoun Mira , Servaes Stijn , Macedo Arthur C. , Vermeiren Marie , Bezgin Gleb , Kang Min Su , Stevenson Jenna , Rahmouni Nesrine , Pallen Vanessa , Poltronetti Nina Margherita , Souza Diogo O. , Soucy Jean‐Paul , Gauthier Serge , Triana‐Baltzer Gallen , Saad Ziad S. , Kolb Hartmuth C. , Schilling Lucas Porcello , Karikari Thomas K , Ashton Nicholas J. , Zetterberg Henrik , Blennow Kaj , Rosa‐Neto Pedro , Pascoal Tharick A. , Zimmer Eduardo R
Published: December 2023

Background

Glial contributions to Alzheimer’s disease (AD) etiology and progression have been increasingly recognized. Experimental and clinical evidence suggests that both microglial activation and astrocyte reactivity have pivotal roles in the progression of tau pathology. However, it remains to be elucidated how microglia and astrocytes complement each other in AD pathogenesis. Here, we tested the associations between reactive astrogliosis and microglial activation with tau phosphorylation and aggregation in individuals across the aging and AD spectrum.

Method

We studied 95 participants (14 cognitively unimpaired [CU] young, 46 CU elderly, and 35 cognitively impaired [CI]) from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort. Individuals had available positron emission tomography (PET) for Aß ([18F]AZD4694), tau tangles ([18F]MK6240), and microglial activation ([11C]PBR28). We further assessed reactive astrogliosis (plasma glial fibrillary acidic protein [GFAP]) and pathological tau phosphorylation (plasma phosphorylated tau [p‐tau] at threonine 231, 181, and 217).

Result

Demographic characteristics of the study population are reported in Table 1. Regression analyses revealed that reactive astrogliosis and microglial activation were synergistically associated with higher plasma phosphorylated tau levels independently of Aß pathology in CU but not CI individuals (Figure 1A). On the other hand, no interactive effects of reactive astrogliosis and microglial activation on tau‐PET burden were observed in either CU or CI individuals (Figure 1B). Similar findings were observed in sensitivity analyses excluding CU young participants.

Conclusion

Our results suggest that reactive astrocytes and activated microglia have Aß‐independent synergistic effects on the early progression of AD pathophysiology by contributing to tau phosphorylation but not tau aggregation. These findings can help to better understand the complementary roles of glial cells in neurodegenerative diseases, as well as provide insights for the development novel therapeutic strategies for AD targeting the interplay between astrocyte and microglial reactivity.
Predicting the chance for being at‐risk of AD based on smartphone data obtained during an everyday wayfinding task in the real world
Authors: Marquardt Jonas , Mohan Priyanka , Spiliopoulou Myra , Glanz Wenzel , Butryn Michaela , Kuehn Esther , Schreiber Stefanie , Maass Anne , Diersch Nadine
Published: December 2023

Background

Patients with Alzheimer’s disease (AD) often show problems in spatial navigation. However, spatial navigation is rarely investigated in real world settings and in people at early disease stages. Capitalizing on recent advancements in digital technologies, we measured the performance of healthy younger (YA) and older adults (OA), as well as older adults with subjective cognitive decline (SCD) while they solved a smartphone‐based wayfinding task.

Method

Using the novel smartphone application “Explore”, we tracked GPS data and other behavioral indicators in 24 YAs, 25 OAs, and 23 SCDs, while they were asked to find points of interest on the medical campus in Magdeburg. In our analyses, we first quantified similarities between the GPS trajectories and identified wayfinding styles using k‐medoids clustering. Next, we extracted navigation profiles with aggregated performance measures as input features (e.g., wayfinding distance and number of help function calls) in a latent profile analysis. Mixed effect models were fitted to evaluate group differences for each performance measure separately. We then fed the performance measure that showed the largest groups differences into a multinomial logistic regression model to predict age and diagnostic group in unknown users via leave‐one‐out cross‐validation.

Result

The GPS data could be clustered into three wayfinding styles. However, the correspondence to our groups was rather low (Figure 1a). In contrast, navigation profiles obtained from the latent profile analysis showed a higher correspondence (Figure 1b). Particularly the number of brief stops during navigation differed between the groups, all p = .006 (Figure 2), and predicted age group, p = .015, and diagnostic group above chance, p = .004 (Figure 3). The leave‐one‐out cross‐validation confirmed the successful prediction of group membership in unknown participants, accuracy = 0.57 (chance level 0.33).

Conclusion

Here, we show how information about the cognitive health status of an individual can be inferred from smartphone‐data, obtained during a brief episode of a frequently performed everyday behavior. In particular, the number of short stops during wayfinding could be used to distinguish between YA, OA, and SCDs. Hence, real‐world navigation data, obtained from mobile devices, might help to identify individuals at increased risk for developing AD.
ConnectShareCare builds connections among care partners of people with serious illness
Authors: O'Donnell Elizabeth A. , Buccelleto Andrea C. , Van Citters Aricca D. , Nelson Eugene C. , King Joel , Holthoff Megan , Kirkland Kathryn B.
Published: December 2023

People living with chronic illnesses naturally turn to peers and community members to address the need for emotional support, practical advice, and quick help with emergent problems. Health systems have been slower to incorporate the expertise that comes from patients and caregivers/ care partners’ lived experience into the design and delivery of care. A coproduction learning health system model aims to draw on the expertise of all to deliver optimal “whole person” care and to capture learning for improvement in the process of care delivery. This model harnesses naturally occurring peer‐to‐peer connections outside the traditional healthcare system into facilitated support networks, which extend the scope of services offered by the health system to support lay care partners, thereby improving their resiliency and inviting them to share their expertise with others. With patients and care partners, we co‐designed and piloted an online facilitated support network, connectsharecare.org, to help persons providing care or support to an adult with a serious illness better prepare to cope with surprises that arise post diagnosis and/or during bereavement. The team prioritized two network functions (1) connecting care partners to information and (2) facilitating emotional support. Between its launch in April 2021 and January 2023 the network has grown to more than 200 members with more than 3,500 posts over 21‐months. Most members report satisfaction with the support and information received, and say that the network helps them find meaning and purpose by supporting others. The most frequently used discussion threads focus on well‐being, emotions, and sources of joy and hope. The network is being adapted and improved as we learn from the data generated. It is feasible to engage a multi‐stakeholder team to co‐design an online peer‐to‐peer facilitated support network for care partners of people with serious illness. ConnectShareCare is valued by care partners. This work has the potential to contribute to a coproduction learning health system for people living with Alzheimer’s disease and other dementias by (1) prioritizing and addressing potentially unique needs of their care partners, (2) generating data for continuous quality improvement, and (3) contributing to scientific knowledge.
Baseline and Six‐Month Actigraphy and Sleep‐monitoring Devices Help Differentiate Between Alzheimer’s Disease and Dementia with Lewy Bodies
Authors: Tsuang Debby W , Brown Karl , Shutes‐David Andrew , Payne Sarah , Jankowski Adrienne , Seto Edmund , St. Louis Erik K , Levendowski Daniel J , Wilson Katie
Published: December 2023

Background

Dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) are challenging to differentiate. Mobile health devices that measure motor and sleep domains between clinic visits may improve differential diagnosis.

Method

Participants with probable AD and probable DLB wore ActiGraph triaxial wGT3X‐BT actigraphy devices on their nondominant wrists for 2 weeks and multichannel Sleep ProfilerX8TM EEG devices on their foreheads for 2 consecutive nights.3 Actigraphy data were processed and scored using GGIR and activity counts in R. The Sleep Profiler characterizes abnormal slow‐wave sleep and non‐REM hypertonia (NRH).

Result

At baseline, participants with DLB (n = 9) had higher UPDRS scores and a higher likelihood of psychosis than participants with AD (n = 8; see Table 1). Using univariate Wilcoxon Rank‐Sum tests, we found that at baseline participants with DLB had lower daily activity counts, higher % time in NRH, and lower % time in REM sleep than participants with AD (unadjusted p‐values < 0.05; See Figure 1). In a recent 6‐month followup, activity levels were lower on average than baseline activity levels for both DLB (n = 5) and AD (n = 5). at 6‐months, the differences in % sleep in NRH increased between DLB participants (n = 5) and AD participants (n = 3) as average % NRH increase 6% in DLB and decreased 1% in AD (see Table 2). These 6‐month differences are not statistically significant, but data collection are ongoing. An exploration of methods for processing and scoring actigraphy data revealed that processing can result in wide range of findings. As a result, we have focused on actigraphy outcomes which are more suitable to older participants with dementia.

Conclusion

Participants with DLB demonstrated lower baseline physical activity and higher rates of baseline sleep disturbances than participants with AD; sleep differences between DLB and AD appeared to increase over 6 months. Actigraphy and sleep‐monitoring devices are well tolerated in participants with dementia and they can reliably collect valid, useful activity and sleep data in between clinic visits.
Ethical social media use for dementia prevention research: Perspectives of research professionals and community members
Authors: Hrincu Viorica , Zaleski Grayden , Robillard Julie M.
Published: December 2023

Background

Ethical social media use underpins effective online engagement for dementia prevention research. Current social media guidelines are broad and lack empirical justification reflecting the values and priorities of the dementia community. By engaging professional and community experts, we seek to identify the ethical parameters of using social media for dementia prevention research.

Method

We conducted semi‐structured, qualitative interviews with professional experts working in dementia research (n = 15; e.g., researchers, coordinators) and experts by experience (n = 14; e.g., persons with lived experience). Experts were from Canada, the USA, the UK, and South America. Discussions were analyzed using thematic qualitative analysis methods.

Result

Professional experts revealed a dearth of ethical guidelines when using social media for research engagement, relying on informal sources of guidance to supplement ethics board approval. Areas identified as needing more attention included privacy concerns, handling instances of misinformation and self‐disclosure, the constraints of prescribed language, and moderating public reactions to posts. Experts by experience appreciated the educational benefits of social media for learning about healthy aging. They valued accessible resources but expressed uncertainty on distinguishing between facts and misinformation. Factors enhancing trust of social media content included transparent presentation, traceable sources, relationship‐building, and partnering with community organizations. Having a family history of dementia was a key motivator for engaging on social media. The negative consequences of diminished online privacy, such as stigma or being targeted for predatory practices, were a major ethical concern. Both groups discussed factors that dampen social media’s theoretical reach to diverse publics, such as existing inequalities permeating digital access (i.e., age, socioeconomic, literacy, English fluency, urban/rural) and past violations undermining trust. Nevertheless, participants cited social media’s wide reach as a societal benefit to improve research participation and awareness of dementia prevention. They acknowledged that younger aging populations have more digital fluency and may benefit more from social media research engagement.

Conclusion

Research professionals and community members identified ethical and contextual factors surrounding the use of social media for dementia prevention, and a need for more guidance. The next project phase will use these data to inform the creation of consensus‐based guidelines for brain health research.
Identifying preclinical Alzheimer’s disease in the community with brief automated hand movement analysis: validation against plasma ptau181 and asymptomatic episodic memory decline
Authors: Alty Jane E , Bai Quan , Wang Xinyi , Li Renjie , Lawler Katherine , George Rebecca J St , Bindoff Aidan D , Roccati Eddy , Bartlett Larissa , Huang Guan , Rudd Kaylee , Collins Jessica M , Garg Saurabh , Hinder Mark , King Anna E , Vickers James C
Published: December 2023

Background

Dementia prevention and drug development is hindered by the lack of low‐cost population‐level tests to help identify preclinical Alzheimer’s disease (AD) in the community. Recent evidence suggests that precise analysis of hand movements may detect motor changes indicative of preclinical AD. The objective was to evaluate how TAS Test, a new online automated hand movement test, predicts preclinical AD biomarkers (plasma ptau181 and subtle episodic memory decline) in a cognitively asymptomatic cohort of older adults.

Method

Participants completed TAS Test online at home using their own computer without researcher assistance: a series of 10‐30 second index finger‐key and index finger‐thumb tapping tests recorded with a keyboard and/or webcam. Movement features including frequency, rhythm, pauses and accuracy were extracted. Participants also completed online tests of episodic memory, CANTAB Paired Associate Learning (CANTAB). A subset provided blood samples for ptau181 analysis. Accuracy of linear regression models comprising hand motor features to predict PAL scores and ptau181 levels, adjusted for confounding, was compared to null models (with only confounders: age, gender, education level, anxiety and depression) using R2adj and AIC. ΔAIC > 2 denotes statistical difference.

Result

1,228 adults (mean (SD) age, 65.8 (7.4) years; 73.0% female) completed TAS Test and CANTAB; 459 underwent ptau181 analysis. All keyboard tests improved prediction of asymptomatic episodic memory decline; the 3 step‐ (ΔAIC = 11.2; R2adj = 8.1%) and alternate‐ key (ΔAIC = 3.3; R2adj = 7.5%) tests ranked highest and were the only keyboard tests to improve prediction of ptau181 (3 step ΔAIC = 7.0; R2adj = 17.8%; alternate key ΔAIC = 3.4; R2adj = 17.4%). All finger‐thumb motor measures improved predictions of CANTAB scores and ptau181 levels; the highest performing tests were dominant hand tapping (CANTAB ΔAIC = 2.9; R2adj = 8.2%; ptau181 ΔAIC = 2.4; R2adj = 12.9%) and both hands dual‐task tapping (CANTAB ΔAIC = 3.0; R2adj = 6.8%; ptau181 ΔAIC = 8.7; R2adj = 11.9%).

Conclusion

TAS Test provides an accessible brief home‐based test for identifying preclinical AD risk. This novel approach holds potential as a pre‐screening/enrichment tool for identifying at risk cohorts for further investigation.
Time for Living & Caring: An Online Intervention to Support Dementia Caregivers’ Use of Respite
Authors: Utz Rebecca , Thompson Amber , Wong Bob , Iacob Eli , Sparks Catharine , Terrill Alexandra , Caserta Michael
Published: December 2023

Background

Because of the demanding care needs associated with dementia, family caregivers often have increasing anxiety and burden over time. Respite, defined as time away from caregiving, is the most requested type of caregiver support and is hypothesized to benefit caregiver wellbeing. However, many caregivers report low respite satisfaction, feeling as though they wasted their time or that they did not know how to use their respite time in a way that benefited them.

Method

Time for Living and Caring (TLC) is a virtual coaching “app” that helps caregivers schedule and plan their respite time. With funding support from NIA (R01‐AG061946), we conducted a pilot test with dementia caregivers (n = 159), randomized into one of two delivery methods – an immediate group that could access all features and functions of the app for 16 weeks, and a delayed‐attention group that received initial instructions on calendaring for 8 weeks and then the more interactive coaching features during the second 8 weeks. This additive “dosing” model where the immediate group received “2 doses” in the first 8 weeks while the delayed‐attention group got “1 dose” initially and “1 dose” during weeks 8‐16 was evaluated using generalized linear modeling on caregiver‐reported anxiety and burden levels over time.

Result

Both immediate and delayed‐attention groups reported 1) increased respite time, 2) increased respite satisfaction, and 3) felt that they were better caregivers because of respite. At 8 weeks, the immediate group did not change in anxiety while the delayed group worsened (p < 0.001). At 16 weeks, the groups were similar in their anxiety levels. By the 20‐week follow‐up period, when neither group had access to TLC, both groups were worsening in their anxiety. Caregiver burden worsened at 16 weeks for the immediate group.

Conclusion

TLC shows potential as an intervention model to improve respite quality and minimize increases in anxiety and burden over time. Intervention delivery that provides additional features or instructions after the initial orientation may keep participants more engaged and result in better caregiver outcomes over time, compared to providing the full set of online resources all at once.
Enhanced Insight into Factors Impacting Driving Ability Across Manual Dexterity, Satisfaction with Managing Daily Activities and Select Cognitive Domains in People with Dementia Associated Disease
Authors: Weller Joanna , Kaczmarek Olivia , Gopie Ian , Bumstead Barbara , Buhse Marijean , Zarif Myassar , Gudesblatt Mark
Published: December 2023

Background

Dementia associated diseases (DAD) refers to a group of disorders characterized by progressive cognitive impairment (CI) that adversely influences ability to function independently in real world activities. CI may reflect abnormalities across multiple cognitive domains (CD) to varying degrees. Successful completion of activities of daily living (ADL) is progressively impaired DAD. Symptom recognition by family and clinicians typically present following irreversible damage, highlighting a demand for effective methods of early DAD diagnosis and treatment. Neurocognitive screening tools combined with patient reported outcomes (PRO) might provide deeper insight into the patterns and progression of DAD. Comparison of PRO across Upper Extremity Function Score (UEF), Self‐Efficacy for Managing Daily Activities (SEMDA), and cognitive performance measures with driving status in PwDAD might enhance understanding of disability across a continuum and identify the medical necessity of transportation assistance for PwDAD.

Method

Retrospective review of examiner independent information collected in the course of routine care of a population of PwDAD including demographics, driving status, UEF, SEMDA, executive function (NT‐EF), and motor function, reflecting time to move and accuracy, (NT‐MF) of a multi‐domain computerized cognitive test (CTB). T‐tests were utilized for analysis with significance (p<0.05).

Result

529 PwDAD (59% female, average age 74.4 +/‐ 8.8 years) provided the data collected to compare patient driving status with UEF, SEMDA, NT‐MF, NT‐EF scores. Statistically significant (p<0.01) relationships were identified between driving status and PRO score for all domains: UEF, SEMDA, NT‐MF, and NT‐EF.

Conclusion

Active driving status in PwDAD is associated with better scores on a self‐reported upper extremity ability profile, self‐efficacy for managing daily activities as well as better executive function and cognitively defined motor function planning. While effective collaboration across a cognitive network provides for driving, simultaneous monitoring of UEF and SEMDA in conjunction with both NT‐MF, and NT‐EF might provide enhanced insight into driving impairment along a continuum. Improved awareness of the multiple potential paths of impairment and real‐world impact can offer proactive opportunities for intervention as well as novel important endpoints to measure therapy efficacy.
Dementia Associated Disorders and Cognitive Impairment – The Relationship of Quantitative Multi‐Domain Computerized Cognitive Testing to Patient Centric Perception of Health Literacy
Authors: Gopie Ian , Kaczmarek Olivia , Weller Joanna , Baek Steven , Bumstead Barbara , Buhse Marijean , Zarif Myassar , Gudesblatt Mark
Published: December 2023

Background

Dementia associated diseases (DAD) refers to clinical conditions characterized by progressive cognitive impairment (CI) that interferes with ability to function independently. However, cognitive impairments can vary in degree and combination of cognitive deficits across multiple cognitive domains. Traditional history and cognitive assessments in clinic are insufficient to identify these varied combinations. Therefore, a clinician may be unaware of these variations and impact on patient QOL and decision‐making. Effective quantitative analysis of cognitive function can be obtained in routine care by a validated, examiner‐independent, sensitive, and reliable computerized cognitive assessment battery (CAB‐NT). Patient reported outcomes (PRO) provide information regarding patient perception of ability across clinically relevant concerns. The BRIEF Health Literacy survey (BHL) PRO is used to find the degree to which one can read, understand, exchange, and use health information and resources. Comparison to computerized cognitive testing has not been explored in this population.

Method

Retrospective cross‐sectional analysis of patients with DAD (PwDAD) who completed both PRO BHL and CAB in routine care on the same day. CAB‐NT included 7 cognitive domains: memory (Mem), executive function (Exe), attention (Att), information processing speed (Inf), visual‐spatial (Vis), verbal function (Ver), motor skills (Mot) and global cognitive summary score (GCS). Linear regression analysis was explored with significance (p<0.05).

Result

329 PwDaD, average age of 70±13 years, 63.2% female. Linear regression was used to analyze trends between BHL and CAB. Significant correlations (p = 0.05) were found for CAB‐NT vs: BHL: GCS‐r = 0.42, Vis‐r = 0.36, Mem‐r = 0.31, Exe‐r = 0.39, Ver‐r = 0.25, Mot‐r = 0.22, Inf‐r = 0.32, and Att‐r = 0.28. One‐way ANOVA was performed between BHL (inadequate, marginal, and adequate) and the cognitive domains of the CAB‐NT. Significant differenced (p = 0.05) were found between the three BHL groups within each cognitive domain.

Conclusion

Patient centric DAD performances on CAB‐NT is related to patient‐reported health literacy. The more impaired the CAB‐NT scores, the poorer patient‐perceived health literacy reported. Patient centric recognition of CI can enhance clinician’s recognition of those people who may require additional information for health‐care decisions or incorporate health‐care proxy for effective shared decision making in routine care. Incorporation of this patient centric information can potentially lead to improved outcomes and satisfaction.
Continuous associations between remote self‐administered cognitive measures and amyloid and tau PET biomarkers of Alzheimer’s disease
Authors: Boots Elizabeth A. , Frank Ryan D. , Fan Winnie Z. , Christianson Teresa J. , Karstens Aimee J. , Kremers Walter K. , Stricker John L. , Machulda Mary M. , Fields Julie A. , Hassenstab Jason J. , Graff‐Radford Jonathan , Vemuri Prashanthi , Jack Clifford R. , Knopman David S. , Mielke Michelle M. , Petersen Ronald C. , Stricker Nikki H.
Published: December 2023

Background

Easily accessible and self‐administered cognitive assessments that can aide early identification of individuals at risk for Alzheimer’s disease (AD) dementia are critical for timely intervention. Mayo Test Drive (MTD) is a remote, self‐administered, multi‐device compatible, web‐based cognitive assessment (Stricker et al., 2022). We investigated continuous associations between MTD and amyloid and tau PET biomarkers and compared the strength of association to PET biomarkers and in‐person cognitive measures.

Method

556 adults from the Mayo Clinic Study of Aging participated (mean age = 70.6; mean education = 16.0 years; 50.7% female; 97.5% white). Participants were predominantly cognitively unimpaired (95.3%; 4.7% had a consensus diagnosis of mild cognitive impairment). Participants completed (1) brain amyloid and tau PET scans, (2) in‐person neuropsychological assessment including Mayo Preclinical Alzheimer’s disease Cognitive Composite (Mayo‐PACC) and Global‐z, and (3) remote MTD comprised of the Stricker Learning Span (SLS) and the Symbols test, which are combined into an MTD composite. Multiple regressions adjusted for age, sex, and education queried associations between imaging biomarkers [amyloid meta‐region of interest (ROI), tau meta‐ROI, and tau entorhinal cortex (EC)‐ROI)] and composite and subtest scores from remote and in‐person measures. Davidson‐Mackinnon J‐test compared R‐squared values of models with remote versus in‐person composites.

Result

Lower performances on MTD composite and Mayo‐PACC were associated with higher amyloid meta‐ROI (p’s<.05; Table 1). MTD composite was also negatively associated with tau meta‐ROI and EC‐ROI (p’s<.05). For memory measures, SLS sum of trials was negatively associated with tau meta‐ROI (p = .01) and EC‐ROI (p<.001) with no associations between AVLT sum of trials and PET (p’s = .06; Table 2). Among processing speed/executive function measures, worse Trails B performance was associated with higher amyloid meta‐ROI (p<.001). Symbols and Digit Symbol Coding were not associated with PET (p’s = .29). A multivariable model with MTD explained significantly less variance (p = .04) for amyloid meta‐ROI (adjusted R‐squared = 0.165) than a multivariable model with Mayo‐PACC (adjusted R‐squared = 0.176); remote and in‐person composite measures were comparable for other associations (p’s>.05).

Conclusion

MTD is associated with continuous measures of amyloid and tau PET biomarkers of AD, demonstrating criterion validity for MTD. Several associations were comparable to relationships between gold‐standard in‐person neuropsychological tests and imaging biomarkers.
Convergent and clinical validity of a remote smartphone‐based self‐assessment of cognition, function, and behavior in early Alzheimer’s disease
Authors: Perumal Thanneer M , Wolfer Arnaud M , Veloso Miguel , Kurniawan Irma T , Aponte Eduardo A , Keita Goullou , Hagenbuch Niels , Shi Beijue , Orfaniotou Foteini , Colell Macarena Garcia Valdecases , Chatham Christopher H , Rey‐Riek Simone , Sink Kaycee M. , Watson David , Boada Mercè , Taylor Kirsten I
Published: December 2023

Background

Trials in early Alzheimer’s disease (eAD) require the quantification of cognitive and functional progression. Compared with traditional in‐clinic assessments, remote assessments via digital health technologies (DHT) enable the collection of a broader palette of cognitive and functional measures at higher frequency and in patients' home environments. However, these must demonstrate validity against standard clinical outcome measures and relevant biomarkers. To this end, the present study aims to determine the reliability, convergent clinical, and functional neuroanatomic validity of a novel DHT, the Alzheimer’s Disease Digital Assessment Suite (AD‐DAS), for individuals on the AD continuum.

Method

In total, 123 participants from 2 countries across 5 sites (3 USA, 2 Spain) participated (https://www.isrctn.com/ISRCTN17035495): 32 healthy controls (HC), 31 amyloid‐PET negative and 30 amyloid‐PET positive subjective cognitive decline (SCDn, SCDP, respectively), and 30 eAD. All participants completed standard in‐clinic neuropsychological assessments and remotely performed the AD‐DAS tasks daily for 28 days without supervision. AD‐DAS comprised 9 active tasks of cognitive/motor functioning and 4 survey questionnaires. Convergent and clinical validity analysis were performed using linear and proportional odds logistic regression modeling with age, sex, education, and site as covariates, respectively. Functional neuroanatomic validity was tested with voxel‐based morphometry (VBM) analyses with anatomic MRIs.

Result

Outcome metrics from all AD‐DAS cognitive/motor tasks correlated with their corresponding clinical comparators (ρpartial (range) = 0.16 ‐ 0.52), supporting their convergent validity. Similarly, outcome metrics from all tasks significantly differentiated the eAD from all the other groups in the expected directions (odds ratio (range) = 0.01 ‐ 61), supporting their clinical validity. The reliability of the outcome metrics ranged from good to excellent (interclass correlation coefficient (range) = 0.71 ‐ 0.91). VBM analyses provided independent and largely confirmatory results, further validating the AD‐DAS.

Conclusion

The AD‐DAS remote, smartphone‐based assessments of cognition show good to excellent test‐retest reliability, and preliminary analyses indicate that they may show convergent, clinical and exploratory functional neuroanatomic validity. Thus, these results provide a foundation for building towards the overarching goals of remote screening, prediction of progression, and monitoring of cognitive decline for future clinical trials and clinical care for preclinical and eAD.
Comparing the Classic Paired Associates Learning Task with a new Smartphone‐Based Version of the Task
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 as has been shown in hundreds of studies over the past two decades. There has been considerable interest in a smartphone version of PAL that can be used remotely, and Cambridge Cognition has now completed work on the first production version of this task. Here, we show how the task compares with classic PAL, in an online within‐subjects study. PAL may be used in repeated assessments, and one notable feature is that performance tends to improve most strongly between a first and second attempt at the task. We therefore included a first smartphone ‘Familiarisation’ session on Day One, before the Days Two and Three web and smartphone sessions.

Method

We obtained PAL scores from 76 adults (43m, 33f) aged 50+ (M = 56.3, SD = 5.46) using the Prolific online cognitive testing platform for this three‐day crossover‐design study. Participants were divided into two groups. In a first ‘Familiarisation’ session, all participants used their smartphones to complete a PAL assessment, then on Day Two, one group used the web‐based assessment, and the other used smartphone assessment, and on the last day each group changed device from the previous day’s session, as well as a questionnaire about their experience and comparison of the task in different devices.

Result

We found that test‐retest reliability between the tasks was very good (Pearson’s r > .7) between the first (‘Familiarisation’) session and Day Two, and then excellent (Pearson’s r > .8) between mobile and web devices on Day Two and Day Three of the study. Next, when comparing performance across the two groups (web‐first, and smartphone‐first), bias was not significant and numerically a very small 0.2 adjusted error points. A significant improvement was seen between Familiarisation and Day Two, but not second and third, supporting the value of a familiarisation session.

Conclusion

We found that the new smartphone version is highly comparable to the classic version of the task, and that familiarisation using PAL on smartphone is effective, generalising across both task versions.
Detecting Unrecognized Cognitive Impairment and Dementias Using Clinical Health Systems Bioinformatics and Electronic Health Records from a National Population
Authors: Khachaturian Ara S , Beeri Michal S , Li Gang , Ravona‐Springer Ramit
Published: December 2023

Globally there are upwards of 35 million people living with dementia and other cognitive impairments, with total annual costs of approximately US$ 1 trillion by 2025. Yet, this estimate does not consider the impact due to the lack of specialized personnel and health care infrastructure to provide timely access for dementia diagnosis, treatment, and care. These factors are complicated by the lack of valid and equitable means for detecting signs of impending cognitive impairment or dementia. Also, these same symptoms are not easily recognized by many primary care physicians who do not make referrals to specialists. These negative dynamics on access to quality brain healthcare may impact under‐represented, underserved, and vulnerable populations at disproportionately greater levels. Although more AD/ADRD interventions will be approved, this will not assure equal market access. There is an immediate need to provide accurate, affordable, appropriate, and equitable clinical care profiles. One approach is to develop digital tools to access electronic health record (EHR) data. Yet, generic EHR data on dementia status are limited to people who have received a formal diagnosis. Worse, in the community setting, most people enduring cognitive impairment or living with dementia will not receive generally a timely diagnosis to support useful clinical care decision‐making. Fortunately, several international health data reservoirs exist that integrate routine EHR data with dementia research‐driven cohort studies with affiliated biobanks, including Sheba Medical Center (SMC) with its ongoing ‐omics and neuroimaging research. As Israel has socialized medicine, and all residents have healthcare provided through the Israeli National Health Insurance law, the Sheba data offers a unique opportunity to develop valid, reliable, and transportable EHR derived assessment tools for cognitive impairment and dementia. The project in collaboration with SMC and Maccabi Healthcare Service—one of four national Israeli medical service providers—demonstrates the advanced capabilities to use electronic medical records linked with a national network of primary care physicians, and the ability to conduct deep‐source data mining in the absence of a clinical diagnosis of cognitive impairment or dementia. The project reports the performance characteristics (i.e., sensitivity and specificity) of assessment tools to detect cognitive impairment or dementia.
Humanoid Mobile Robots and wearable sensors improve the quality of care and address worker shortages in nursing homes
Authors: Khan Arshia A
Published: December 2023

Background

Technology has been identified as a solution to address the growing healthcare worker shortages(Harp, 2023). Humanoid robots have great potential to help augment care in elderly and people affected with dementia (Khan & Anwar, 2020; Joseph et.al, 2018). Humanoid robots and wearable sensors were deployed in eight nursing homes to help address healthcare worker shortages and augment care of elderly and people affected with dementia. The resident satisfaction and quality of life annual survey conducted by the Minnesota Department of Human Services revealed an improved satisfaction and quality of life in the domain of activities in the nursing homes that deployed robots when compared to the nursing homes that did not deploy the robots. The pre and post data gathered revealed that the residents felt happier, more cared for, less tired and less frustrated after interacting with the robots. The staff feedback indicates that the staff had time to address their chores while the robots engaged teh residents.

Method

Two humanoid robots and ten wearable sensors per facility were deployed in 8 different nursing homes. The robots were programmed to address the domains of physical, emotional/social and cognitive wellbeing. Four forms of data ‐ 1) nursing home resident satisfaction and quality of life data gathered by the Minnesota Department of Human Services; 2) pre and post surveys conducted before and after interactions with the robots; 3) weekly feedback was from the healthcare staff and wearable sensor data.

Result

The nursing home resident satisfaction and quality of life data gathered annually by the Minnesota Department of Human Services revealed improvement in the satisfaction and the quality of life domain of activities in the nursing homes that deployed humanoid robots versus the nursing homes that did not deploy humanoid robots. The pre and post surveys conducted before and after the interactions with the robots showed 17.4% improvement in their happiness, 4.3% more cared for,10% less tired and 14.5% less frustrated after engaging in the activities with humanoid robots.

Conclusion

Humanoid robots and wearable sensors have proved to help improve the quality of life of elderly.
Identifying modifiable psychosocial outcomes to maintain physical ACTIVity and promote independence in DEMentia: the ActivDem study
Authors: Ardle Ríona Mc , Din Silvia Del , Hicks Ben , Kingston Andrew , Banerjee Sube , Thomas Alan J , Robinson Louise , Rochester Lynn
Published: December 2023

Background

Promoting habitual physical activity (HPA; e.g. walking) may help decelerate dependency and disability in people with dementia (PwD). HPA refers to any movement the skeletal muscles make which requires energy expenditure, including daily tasks (e.g. gardening/housework). Research regarding physical activity in PwD mainly focuses on exercise‐based activities, which may not be feasible for people with chronic health conditions or frailty, or who cannot afford or travel to exercise classes. Promoting participation in HPA may be an inclusive, accessible strategy to support PwD to remain physically active and mobile. PwD participate in less HPA than recommended and disease‐specific factors (e.g. cognition) do not sufficiently explain this. In healthy ageing, HPA participation is associated with multiple socio‐ecological factors (e.g. psychosocial wellbeing/social support/environment) but this has not been explored in dementia. The ActivDem study aims to identify key socio‐ecological influences on HPA change over time in community‐dwellers with dementia. Figure 1 presents ActivDem’s core objectives.

Method

PwD and their carers will be recruited from the ongoing cohort study, DETERMIND, they will participate in a continuous seven‐day HPA assessment. This involves wearing an inertial measurement unit on their lower back at baseline and one‐year follow up. Digital mobility outcomes relating to volume (e.g. steps per day), pattern (e.g. mean ambulatory bout length), and variability (i.e. of bout length) will be derived via validated algorithms. PwD will also complete the LASA Physical Activity Questionnaire and Falls Efficacy Scale. Carers will complete the Dementia Management Strategies Scale. Demographic, clinical and psychosocial characteristics and information on care support will be assessed as part of the DETERMIND study (1).

Result

Longitudinal statistical methods will identify key predictors of HPA change in PwD, and examine the relationship between HPA and independence

Conclusion

The ActivDem study will identify key socio‐ecological predictors of HPA change, these will inform key interventional components to support PwD to remain physically active and mobile following diagnosis of dementia. References • Farina et al., 2020. DETERMinants of quality of life, care and costs, and consequences of INequalities in people with Dementia and their carers (DETERMIND): A protocol paper. Int. J. Geriatr.
Comparing intra‐individual variability on executive functioning tasks in individuals with Mild Cognitive Impairment and Dementia of the Alzheimer Type: Results from the ARMADA Study
Authors: Ho Emily , Karpouzian‐Rogers Tatiana , Dworak Elizabeth , Weintraub Sandra , Gershon Richard C.
Published: December 2023

Background

Cognitive decline is most often assessed mean group differences on static measures of cognitive abilities (MacDonald et al., 2009). Another, perhaps more dynamic, method to understanding cognitive functioning is to evaluate variability in performance within an individual, termed intraindividual variability (IIV), which has been associated with reduction in gray matter and less efficient cognitive processing. Using results from a multi‐site, longitudinal ARMADA study that validated NIH Toolbox across the cognitive aging spectrum, we investigated whether IIV in reaction time processing can differentiate between older adults with normal cognition, mild cognitive impairment (MCI), or dementia of the Alzheimer type (DAT), as well as the relative magnitude of differences between groups.

Method

As part of the Advancing Reliable Measurement in Alzheimer’s Disease and cognitive Aging study (ARMADA; Weintraub et al 2020), participants completed the NIH Toolbox Cognition Battery, including two measures of executive functioning, Dimensional Change Card Sort and Flanker Inhibitory Control, which include granular reaction time data in milliseconds. We analyzed standard deviation and mean absolute deviation of item‐level data of all trials, correct trials only, and incorrect trials only for three groups: normal controls, those with amnestic MCI, and those with mild DAT.

Result

We observe large effect sizes of reaction time by clinical group, with the mild DAT group demonstrating mean standard error across trials of approximately .5 seconds throughout, compared with .25 seconds for MCI and .10 seconds for the control group (Figure 1). This translates to an approximate 5‐fold increase in processing speed in the most severe clinical group. Examining time trends, we see that while the NC and MCI group were faster as the test progressed; there is no similar learning effect for the mild DAT group. Similar effect sizes were observed for the Flanker test.

Conclusion

This study represents one of the first studies to examine clinical performance using process data from two executive functioning measures on the NIH Toolbox across the cognitive aging spectrum. Future work will explore more definitions of IIV to determine which measure will maximally differentiate between established clinical groups and examine longitudinal differences.