bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seas the day: Co‐designing immersive virtual reality exergames with exercise professionals and people living with dementia
Authors: Mehrabi Samira , Muñoz John E , Basharat Aysha , Li Yiru , Middleton Laura E , Cao Shi , Barnett‐Cowan Michael , Boger Jennifer 
Published: December 2021

AbstractBackgroundPhysical activity (PA) is associated with physical and cognitive benefits among people living with dementia or mild cognitive impairment (PLWD/MCI) and is a meaningful activity that can improve their confidence in everyday life. Exercising in virtual reality environments (VR Exergame) is becoming an increasingly feasible and enjoyable way to promote PA and well‐being in PLWD/MCI. Although co‐design can significantly improve the design of technology, it is rarely done with PLWD/MCI. This study uses participatory design methods and collaborative approaches to involve key stakeholders to develop and test a VR Exergame "Seas the Day", a novel solution targeting PLWD/MCI well‐being.MethodsA multi‐stage, user‐centered co‐design approach was used to custom‐build VR Exergames tailored to the unique needs and abilities of PLWD/MCI based on a first generation of the prototype that was previously developed and tested with PLWD/MCI. This paper describes the next iteration of the prototype. Processes included concept ideation and brainstorming activities, iterative prototyping, and playtesting/input/feedback sessions with key stakeholders (PLWD/MCI, exercise professionals, engineers, VR game designers, content developers).ResultsThe multidisciplinary and collaborative design process occurred over 15 months (overlapping with COVID‐19 pandemic) with 7 PLWD/MCI (6 females; M=81.3 years) and 9 exercise professionals (7 females; M=38.1 years) to date. The game was designed to target movements identified by exercise professionals and researchers (aerobic exercises, range of motion, seated‐balance, quick response to stimuli) and is structured in three exercise stages (warm‐up, conditioning, cool‐down). To ensure safety of participants while using VR headsets, only seated upper‐limb exercises were targeted. Stakeholder feedback regarding game mechanics, aesthetics, and visual/auditory cues were gathered during brainstorming and playtesting sessions and implemented into specific game‐related scenarios (tai‐chi, rowing, fishing).ConclusionWe presented the process, outcomes, and challenges of adopting a participatory/collaborative approach with multiple stakeholder groups to co‐design VR Exergames tailored to PLWD/MCI. Next steps will include a mixed‐method evaluation of the VR Exergames among community‐dwelling older adults and PLWD/MCI in retirement communities and long‐term care to evaluate: i) feasibility and acceptability of use, ii) game user experience, iii) barriers/facilitators to uptake of VR Exergames; and iv) inform/validate VR Exergames gameplay metrics reflective of cognitive and motor performance.
Traumatic brain injury accelerates Parkinson’s disease onset without altering Parkinson’s neuropathology
Authors: Spiegel Jonathan , Sone Je Yeong , Butler Tracy , Pirraglia Elizabeth , de Leon Mony J 
Published: December 2021

AbstractBackgroundTraumatic brain injury (TBI) is a well‐established risk factor for Parkinson’s disease (PD), though the nature of this relationship remains unclear. This study examines TBI’s relationship with the AAO of and survival following PD onset among participants with PD and examines TBI’s relation with PD neuropathology in an autopsy cohort.MethodsThis is a retrospective observational study using the National Alzheimer’s Coordinating Centers (NACC) database. TBI status was assessed based on self‐reported history. Clinicians estimate was used for determining age at onset (AAO) of cognitive decline and autopsy examination was used in assessing degree of substantia nigra neuropathology. The most recent assessment of participants was used as of June 2018, including participant visits which occurred between 2005 and 2018. The NACC dataset includes a 423 (53 TBI+) participants diagnosed with PD. Substantia nigra neuropathology was assessed in 1,133 (150 TBI+) participants, selected without regard to antemortem diagnoses.ResultsTBI was associated with a 4.9 (1.5‐8.2) year earlier AAO of PD and a 5.9 (3.0‐8.8) year longer survival with PD, but not with death age or severity of substantia nigra pathology.ConclusionsTBI appears to accelerate PD onset without altering death age or PD‐related neuropathology. This relationship suggests that TBI lowers the threshold required for PD pathology to present as symptomatic PD.
Semi‐quantitative assay for neurogranin peptides using IP‐MALDI‐MS
Authors: Kaneko Naoki , Takahashi Ryota , Korenaga Akihito , Yoda Ritsuko , Sekiya Sadanori , Iwamoto Shinichi , Tanaka Koichi 
Published: December 2021

AbstractBackgroundNeurogranin (Ng) is a cerebrospinal fluid (CSF) biomarker for synaptic dysfunction at early stage of Alzheimer’s disease (AD). It has been reported that a variety of truncated peptides from Ng is increased in AD brain tissue. However, the clinical significance of Ng peptides in plasma has remained unclear. We have developed a simultaneous detection method of a plurality of amyloid βpeptides in plasma by using immunoprecipitation combined with matrix‐assisted laser desorption ionization time‐of‐flight mass spectrometry (IP‐MALDI‐MS) (Kaneko et al., Proc Jpn Acad Ser B Phys Biol Sci. 2014). In this study, we applied the IP‐MALDI‐MS technique to Ng measurement.MethodNg peptides and proteins were immunoprecipitated from human plasma or standard sample spiked by stable isotope‐labeled (SIL) Ng50‐78 using magnetic beads coupled with anti‐Ng monoclonal antibody. After the IP was performed two times consecutively, Ng proteins and peptides eluted from antibody beads were applied on the MALDI plate. SIL‐Ng50‐78 was used as an internal standard for normalizing an intensity of each Ng peptide.ResultWe optimized the condition such as a kind of detergent and an amount of antibody beads in IP for enhancing Ng signal intensity in MS. In the examination of detergents, UDM showed the highest sensitivity among six tested detergents. Using IP‐MALDI‐MS, we tried to detect Ng peptides and proteins in human plasma. As a result, some peaks corresponding to a variety of Ng peptides (m/z m/z > 5000.0) were detected in a plasma sample. To evaluate our semi‐quantitative assay using the internal standard, we selected some Ng peptides with low and high mass (m/z 2331.5–4084.7) to examine a linearity of the normalized intensity of Ng peptides. The accuracy in linear regression model showed within 80‐120% over a range of 5–160 pM in Ng48‐75 and 10‐160 pM in Ng50–78 and Ng33–75. Intra assay precision of Ng peptides in plasma was less than 20%CV.ConclusionIP‐MALDI‐MS enable the highly sensitive and simultaneous semi‐quantitative measurement of multiple Ng peptides levels. It could be helpful in the analysis of plasma Ng peptides for AD biomarker.
Influence of lifespan cognitive reserve indicator on cognitive trajectories in different domains: role of brain pathologies
Authors: Li Xuerui , Song Ruixue , Xu Hui , Yang Wenzhe , Qi Xiuying , Kivipelto Miia , Bennett David A , Xu Weili 
Published: December 2021

AbstractBackgroundEvidence on the association of the cognitive reserve (CR) with the cognitive trajectories is limited. We examined the influence of lifespan CR indicator on domain‐specific cognitive trajectories taking brain pathologies into account.MethodWithin the Rush Memory and Aging Project, 1,697 dementia‐free participants (mean age: 79.6 years) were followed up to 21 years. Lifespan CR indicator encompassing education, early‐life, mid‐life, and late‐life cognitive activities, and late‐life social activities was ascertained at baseline and categorized by tertiles (lowest, middle, and highest). Global cognition, episodic memory, semantic memory, working memory, visuospatial ability, and perceptual speed were assessed annually with 19 tests battery, from which composite scores were derived. During the follow‐up, 648 died and underwent autopsies, and brain pathologies were assessed. Data were analyzed using linear mixed‐effects models.ResultAmong all participants, the score of CR indicator ranged from ‐8.00 to 5.74 (mean: 0.00±2.23). In multi‐adjusted mixed‐effects models, compared to the lowest CR, the highest CR was related to slower decline in global cognition (β=0.028, 95% confidence interval [CI]: 0.012 to 0.043), episodic memory (β=0.028, 95% CI: 0.010 to 0.047) and working memory (β=0.019, 0.005 to 0.033) during the follow‐up. Moreover, the association of the highest CR with cognitive function changes remained significant among participants with high Alzheimer’s disease pathology or gross infarcts.ConclusionHigh lifespan CR indicator is associated with preserved global cognitive function, episodic memory, and working memory over time, even in the presence of brain pathologies.
Patient, disease, and study characteristics in contemporary dementia research: A systematic review on external validity
Authors: Mooldijk Sanne S , Licher Silvan , Wolters Frank J 
Published: December 2021

AbstractBackgroundFor informed decision making on diagnosis, prognosis and care of dementia, physicians and patients rely on the transportability and applicability of evidence from published studies into daily clinical practice. It is uncertain, however, whether routine clinical assessment of dementia is sufficiently captured in contemporary research.MethodWe systematically reviewed PubMed/Medline to characterise study populations in contemporary dementia research by capturing one calendar year of dementia research in humans. We included all studies with patients with dementia that were published in any language in the top 100 journals in the categories clinical neurology, neurosciences, geriatrics & gerontology, psychiatry, neuroimaging, or general & internal medicine between September 1, 2018 and August 31, 2019. Key study details were extracted by 2 reviewers, such as study setting, number of participants, age at dementia diagnosis, and use of imaging or biomarker modalities. Potential discrepancies were resolved by an independent, third reviewer.ResultAmong a total of 513 identified studies, 211 (41%) included <50 individuals with dementia. The remaining 302 studies included a median of 214 patients (interquartile range (IQR): 98‐628) with a mean age at diagnosis of 74.1 years (standard deviation (SD): ±8.0). Age differed substantially with study base, such that patients in clinical studies were on average 71.8 years (±6.4; n=180) at time of diagnosis, compared to 80.6 years (±4.7; n=79) in population‐based studies (mean difference: 8.8 years, 95% confidence interval: 7.3‐10.2; figure 1). Use of MRI, PET and CSF, but not blood biomarkers, was limited to clinical studies (80‐96%), and consequently applied to relatively young patients (mean age: 71.6 years). Studies mainly originated from North America and Western Europe (figure 2); in the 22% of all studies that reported on ethnicity, the vast majority of participants were of Caucasian descent (median: 90%, IQR: 79‐97). The three most studied cohorts represented 21% of all included study populations.ConclusionContemporary dementia research is limited in terms of ethnic and geographic diversity, and draws largely from clinical populations with relatively young patients. Greater inclusivity as well as deeper phenotyping in unselected cohorts could benefit diagnosis and development of effective treatment for all patients with dementia.
Test‐retest variability of relative tracer delivery rate as measured by [11C]PiB
Authors: Heeman Fiona , Hendriks Janine , Alves Isadora Lopes , Tolboom Nelleke , Van Berckel Bart N.M. , Yaqub Maqsood , Lammertsma Adriaan A. 
Published: December 2021

AbstractBackgroundIn Alzheimer’s disease (AD), reductions in cerebral blood flow (CBF) have been reported and these may be used as proxy for measuring treatment efficacy or disease progression. The gold standard technique for measuring CBF is [15O]H2O positron emission tomography (PET). Recent studies, however, have reported high correlations between [11C]PiB PET derived relative tracer delivery rate R
1 and [15O]H2O derived relative CBF, suggesting that [11C]PiB R
1 may be a good proxy of relative CBF. As longitudinal PET studies become more common for measuring disease progression, it is important to know the intrinsic variability of R
1. The purpose of the present study was to determine R
1 test‐retest (TRT) variability.MethodPreviously, TRT variability of [11C]PiB binding potential has been reported for a group of twelve participants (five cognitively unimpaired (CU), one with mild cognitive impairment and six with AD dementia), in which all participants underwent two 90 min [11C]PiB PET scans using a Siemens ECAT EXACT HR+ scanner1. This dataset was reanalysed to also determine TRT variability of [11C]PiB R1. The voxel‐based implementation of the two‐step simplified reference tissue model with cerebellar grey matter as reference tissue was used to generate R1 images. Next, TRT variability was calculated both globally and regionally, and global R1 measures were compared between diagnostic groups using a non‐parametric Mann‐Whitney U test. Next, correlation analysis was used to assess the relationship between TRT variability and regional volume. Finally, regional test and retest R1 measures were compared using Linear Mixed Effect Models and Bland‐Altman analysis.ResultGlobal relative tracer delivery (R1) was significantly lower in AD patients (test R1:0.82±0.04, retest R1:0.82±0.03) compared with CU participants (test R1:0.93±0.04 retest R1:0.91±0.03, p<0.01). TRT variability was low across regions (range:1.5‐5.8%), with a trend effect towards smaller TRT for larger regions (R2=0.14, p=0.09). Furthermore, test and retest measures showed high, significant correlations (R2=0.92, slope=0.98) and negligible bias (0.69±3.07%).ConclusionThe high precision of [11C]PiB R1 suggests suitable applicability for cross‐sectional and longitudinal studies. This finding further demonstrates the utility of dynamic [11C]PiB PET scans for dual‐biomarker imaging in AD research. Reference: Tolboom et al.(2009) Eur J Nucl Med Mol Imaging 36:1629‐38.
Classification of AD/MCI/HC based on amyloid‐PET using Random Forest Ensemble
Authors: Bao Yiwen , Chiu Patrick Ka‐Chun , Shea Yat Fung , Kwan Joseph S.K. , Chan Hon Wai Felix , Mak Henry 
Published: December 2021

AbstractBackgroundPositron emission topography (PET) and magnetic resonance imaging (MRI) are two common in‐vivo techniques for supporting clinical diagnosis of dementia. The correlated neuropathological changes including amyloid‐beta (Aβ) deposition, and cortical atrophy may have the potential to predict conversion from cognitively normal elderly adults (HC), to mild cognitive impairment (MCI) and eventually Alzheimer’s disease (AD). In order to overcome the complex interactions among these biomarker datasets, random forest (RF) as one of the machine learning algorithms is usually used in data classification. In current study, we aim at evaluating the accuracy of RF model in distinguishing HC, MCI from AD and the importance of various neuropathological features in selection.MethodThree cohorts were included in our study. We recruited 94 AD, 82 MCI and 85 HC from GAAIN (The Global Alzheimer’s Association Interactive Network) database, AIBL (Australian imaging, biomarkers and lifestyle) database, and our memory clinic database. Based on Centiloid pipeline, we processed the co‐registered MRI and PET images of each subject. Additionally, to compare quantitative amyloid load across different tracers, we converted SUVR (Standardized Uptake Value Ratio) values into standard Centiloid units. RF algorithm was performed on Python via scikit‐learn package. Finally, 122 regional volumes, 68 regional cortical thicknesses, 16 small regional amyloid distribution and 1 global amyloid load were input as features.ResultIn Table 1, the AUC value was highest (AUC=0.82) in the classification between HC and AD, intermediate (AUC=0.78) between HC and MCI and lowest (AUC=0.65) between AD and MCI. In each binary classification, sensitivity‐71%, specificity‐85%, accuracy‐78%; sensitivity‐88%, specificity‐76%, accuracy‐81% and sensitivity‐86%, specificity‐44%, accuracy‐66% were achieved in differentiating MCI from HC, AD from HC and AD from MCI respectively. For importance ranking of features within the model, 6 features of regional cortical thickness and 4 features of regional volume were found in the classification between HC and MCI, while all 10 essential features belong to regional Aβ ‐ROI in classification between HC and AD as well as MCI and AD (Table 2).ConclusionRandom forest model using regional volume, regional cortical thickness and amyloid load (in Centiloid unit) had moderate to high accuracy in differentiating AD from HC and MCI.
Social behavior assessment in cognitively impaired older adults using a passive and remote smartphone application
Authors: Muurling Marijn , Reus Lianne M. , de Boer Casper , Jagesar Raj , Vorstman Jacob A , Kas Martien JH , Visser Pieter Jelle 
Published: December 2021

AbstractBackgroundIn Alzheimer’s Disease (AD), loss of social interactions has a major impact on well‐being. Therefore, AD patients would benefit from early detection of symptoms of social withdrawal. Current measurement techniques such as questionnaires are subjective and rely on recall, in contradiction to smartphone applications, which measure social behavior passively and objectively. Here, we examine social interactions through passive remote monitoring with the smartphone application BEHAPP in cognitively impaired participants. This study aims to investigate (1) the association between demographic characteristics and BEHAPP outcome variables in cognitively normal (CN) older adults, (2) if social behavior as measured using the passive smartphone app BEHAPP is impaired in cognitively impaired (CI) participants compared to subjects with subjective cognitive decline (SCD), and CN older adults. In addition, we explored in a subset of individuals the association between BEHAPP outcomes and neuropsychiatric symptoms.MethodCN (n=209), SCD (n=55) and CI (n=22) participants, older than 45 years, installed the BEHAPP app on their own Android smartphone for 7‐42 days. CI participants had a clinical diagnosis of mild cognitive impairment or AD‐type dementia. The app continuously measured communication events, application usage and location. Neuropsychiatric Inventory (NPI) total scores were available from 20 SCD and 22 CI participants.ResultWe found that older cognitively healthy participants called less frequently and made less use of apps. No sex effects were found. Linear models corrected for age, sex and education showed that compared to the CN and SCD groups, CI participants called less unique contacts and contacted the same contacts relatively more often (Figure 1). They also made less use of apps, visited less unique places and traveled less far from home. Higher total NPI scores were associated with more unique stay points and further travelling. Similar behavior patterns were found when correcting for multiple comparisons.ConclusionCognitively impaired individuals show reduced social activity, as measured by the smartphone application BEHAPP. Neuropsychiatric symptoms seemed only marginally associated with social behavior as measured with BEHAPP. This research shows that a passive and remote smartphone application is able to objectively and passively measure altered social behavior in a cognitively impaired population.
Community paramedic‐delivered care transitions intervention reduces emergency department revisits among cognitively impaired patients
Authors: Shah Manish N , Green Rebecca K , Jacobsohn Gwen C , Jones Courtney MC , Caprio Thomas V , Cochran Amy L , Cushman Jeremy T , DuGoff Eva , Lohmeier Michael , Kind Amy J 
Published: December 2021

AbstractBackgroundUp to half of community‐dwelling older adults with impaired cognition who are discharged home from the emergency department (ED) return for further care within 30 days. We examined the effects of delivering the Care Transitions Intervention (CTI) to older adult patients with impaired cognition discharged home from the ED, hypothesizing that the CTI would decrease ED revisits in the following 30 days.MethodWe conducted a pre‐planned sub‐analysis of community‐dwelling older adults (age≥60 years) with impaired cognition participating in a single‐blind, randomized controlled trial testing the effectiveness of the CTI adapted for use following ED discharge. The parent study recruited ED patients from three university‐affiliated hospitals from 2016–2019. Subjects eligible for this analysis had to: 1) have a primary care provider within these health systems; 2) be discharged to a community residence; 3) not receive care management or hospice services; and 4) be cognitively impaired in the ED, as determined by a score>10 on the Blessed Orientation Memory Concentration Test. Intervention group subjects received a home visit from a trained paramedic coach within 72 hours of discharge, and up to three follow‐up phone calls during the following month. Our primary outcome was occurrence of any ED revisit within 30 days of discharge. Secondary outcomes included any ED revisit within 14 days and outpatient clinic follow‐up. We evaluated intervention effects using multivariate logistic regression.ResultOf our sub‐sample (N=81, 36 control, 45 treatment), 57% were female and the mean age was 78 years. Bivariate comparison of primary and secondary outcomes found no significant differences. Multivariate analysis, adjusted for the presence of moderate to severe depression and inadequate health literacy, found that the CTI significantly reduced the odds of a repeat ED visit within 30 days (OR 0.25, 95%CI 0.07‐0.90) but not 14 days (OR 1.01, 95%CI 0.26‐3.93). Multivariate analysis of outpatient follow‐up found no significant effects.ConclusionCommunity‐dwelling older adults with cognitive impairment receiving the CTI following ED discharge experienced fewer ED revisits within 30 days compared to usual care. Further studies must confirm and expand upon this finding, identifying features with greatest benefit to patients and caregivers.