bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multimodal data collection in Alzheimer’s disease: Participant acceptance of various digital technologies employed in the MEDIA study
Authors: Sorinas Jennifer , Curcic Jelena , Vallejo Vanessa , Sverdlov Oleksandr , Piksa Mateusz , Erdemli Gul , Praestgaard Jens , Snædal Jón , Cha Jang‐Ho , Hannesdottir Kristin , Team MEDIA Study 
Published: December 2022

AbstractBackgroundThe rate of failed drug trials in Alzheimer’s disease (AD) remains high. Many conventional endpoints currently used to demonstrate success of clinical trials lack sensitivity to drug treatment effects and perform disparately across disease stages. These endpoints tend to be burdensome “single time‐point” assessments that are vulnerable to subjectivity and rater errors.Novel technologies are rapidly emerging at the same time as our understanding of how to optimally measure drug treatment effects is evolving. Rather than relying on reductionist paper‐pencil assessments, a multimodal approach incorporating more frequent and/or more direct physiological assessments, may result in better detection of true treatment effects. However, will such an approach add too much burden to clinical trials? Are elderly participants in AD trials willing and able to operate new technologies? It is clear that any endpoint that is not well‐accepted by sites or trial participants is unlikely to be successfully adopted for large clinical drug trials.MethodThe MEDIA study was a single‐site study evaluating 10 digital in‐clinic assessments in 38 early AD participants and 12 cognitively healthy controls. The assessments included computerized and augmented reality assessments as well as wearable gait and EEG monitoring. This study additionally included conventional cognitive assessments augmented with unobtrusive digital sensors; such as eye tracking via a tablet camera, speech analytics using voice recordings and physiological assessments using a tablet or pen with built‐in sensors. All participants completed a feedback survey on each of the digital assessments. This feedback survey asked seven questions about ease of use, burden of the assessment and clinical meaningfulness. Responses were recorded on a scale of 0 = strongly disagree to 5 = strongly agree.ResultThe results revealed overall good acceptance of the digital technologies. Although some of the assessments were considered mentally demanding, the majority of participants felt the technologies were easy to use, clinically meaningful and enjoyable.ConclusionThere is great anticipation for more sensitive clinical endpoints in AD. However, a question remains on the operational feasibility and how acceptable digital endpoints are to trial participants. This presentation discusses early AD participant (from presymptomatic to mild dementia) acceptance of different digital assessments.
Neuropsychological assessment in the multicultural memory clinic: development and feasibility of the TULIPA battery
Authors: Franzen Sanne , van den Berg Esther , Bossenbroek Willemijn , Kranenburg Judi , Scheffers Esther , van Hout Moniek , van de Wiel Lotte , Goudsmit Miriam , van Bruchem‐Visser Rozemarijn L. , van Hemmen Judy , Jiskoot Lize C. , Papma Janne M. 
Published: December 2022

AbstractBackgroundNeuropsychological assessment of culturally diverse populations is hindered by barriers in language, culture, education, and a lack of suitable tests. Furthermore, individuals from diverse backgrounds are often unfamiliar with being cognitively tested. The aim of this study was to develop a new neuropsychological test battery and study its feasibility in multicultural memory clinics.MethodComposition of the TULIPA battery (Towards a Universal Language: Intervention and Psychodiagnostic Assessment) entailed a literature review and consultation with experts and individuals from diverse backgrounds. Feasibility was investigated by examining administration and completion rates and the frequency of factors complicating neuropsychological assessment in 345 patients from 37 countries visiting four multicultural memory clinics in the Netherlands.ResultThe test battery included existing tests such as the Cross‐Cultural Dementia screening (CCD), Rowland Universal Dementia Assessment Scale (RUDAS), and tests from the European Cross‐Cultural Neuropsychological Test Battery, and newly developed tests. Completion rates for the test battery were generally high (82%‐100%), except for CCD Dots subtest B (58%). Although tests of the ‘core’ TULIPA battery were administered often (median: 6 of 7, IQR: 5–7), supplementary tests were administered less frequently (median: 1 of 9; IQR: 0–3). The number of administered tests correlated with disease severity (RUDAS, ρ = .33, adjusted p<.001), but not with other patient characteristics. Complicating factors were observed frequently, e.g., suboptimal effort (29%‐50%), fatigue (29%), depression (37%‐57%).ConclusionThe TULIPA test battery is a promising new battery to assess culturally diverse populations in a feasible way, provided that complicating factors are taken into account.
Domain‐specific self‐ and informant‐reported cognitive complaints across the Alzheimer’s disease spectrum
Authors: Cacciamani Federica , Godefroy Valérie , Brambati Simona M , Migliaccio Raffaella , Montembeault Maxime 
Published: December 2022

AbstractBackgroundA growing number of studies are currently investigating whether Subjective Cognitive Decline (SCD) may represent an early indicator of Alzheimer’s disease (AD). Due to the high frequency of amnestic AD dementia, SCD research is highly focused on episodic memory. Non‐amnestic complaints are less studied, although patients or their families often report difficulties in retrieving words, planning or spatial orientation, to name a few (e.g., Valech et al., 2018, J Alzheimers Dis). Furthermore, few studies have investigated which source of complaint is the most accurate. In this study, we aimed to measure how accurately self‐ and informant‐reported complaints in different cognitive domains can discriminate individuals along the AD continuum and controls.MethodWe selected four groups of participants from the ADNI cohort: amyloid‐positive (Aβ+) individuals with AD, mild cognitive impairment (MCI) or cognitively normal (CN), and amyloid‐negative (Aβ‐) CN controls. Self‐ and informant‐reported complaints were measured with the Everyday Cognition questionnaire in four domains, namely, memory, language, visuospatial abilities, and executive functions. Receiver operating characteristic curves analysis was performed to evaluate the accuracy of the ECog scores in discriminating the groups.ResultSelf‐ and informant‐reported complaints were distributed as follows: memory, language, executive, and visuospatial (from the most severe to the least severe). ECog‐Subject scores globally distinguished groups little better than chance. The Memory score performed best among the ECog‐Subject scores, but the accuracy was low to moderate. In the other three domains, most AUCs were below 0.70 and specificities always below 70%. All ECog‐StudyPartner scores (i.e., in all four cognitive domains) could discriminate MCI and AD from CN, as well as AD from MCI, with good to excellent accuracy (all AUCs between 0.72 and 0.98). However, no ECog‐StudyPartner score seemed useful in distinguishing Aβ+/CN and Aβ‐/CN subjects (all AUC<0.55, all specificity indices <0.22).ConclusionSelf‐reported SCD may have limited utility for both early diagnosis and the inclusion of subjects in research protocols. Individuals with early‐stage AD may already present reduced awareness of their cognitive decline (e.g., Cacciamani et al., 2021, Alzheimer’s Res. Ther). For this reason, it seems crucial to consider informant‐reported complaints, both amnestic and non‐amnestic.
Scaling Comprehensive Dementia Care
Authors: Super Nora 
Published: December 2022

AbstractBackgroundDespite scientific progress over the last 25 years, dementia remains one of the toughest health‐care challenges. Alzheimer’s disease is the sixth‐leading cause of death in the United States, and the number of deaths from all related dementias may be twice as high.[i] Years of investment and research in Alzheimer’s disease and related dementias (ADRD) are sowing seeds of hope. New treatments aim to slow cognitive decline and manage symptoms. However, because of the complexity of dementia, people living with dementia will likely need a combination of therapeutic treatments, coordinated care, and supportive services to help them live their lives to the fullest post‐diagnosis.MethodThe Milken Institute Alliance to Improve Dementia Care convened a roundtable in June 2021. Leaders across industry, government, research, advocacy, philanthropy, health systems, and community‐based organizations explored ways to improve and pay for comprehensive dementia care. Through a consensus‐driven process, we produced a report that presents actionable recommendations to improve post‐diagnostic care and payment policies under traditional Medicare.[i][i] Nora Super, Rajiv Ahuja, and Mac McDermott,” Milken Institute, November 2021: https://milkeninstitute.org/report/dementia‐care‐models‐scaling‐comprehensiveResultBased on extensive desktop research, the roundtable convening, and consultation with a working group of experts, we identified five high potential action steps.1. Ensure all dementia‐care models contain a minimum set of core elements for comprehensive care and follow a population‐health approach that tiers services to level of need2. Implement quality measures to evaluate access, utilization, and outcomes of comprehensive dementia‐care models, particularly for diverse communities disproportionately impacted by dementia and their caregivers3. Expand dementia‐specific training beyond physicians and nurses to increase interprofessional coordination, provide continuous monitoring and assessment, and expand access to high‐quality, dementia‐care services4. Test implementation of payment models for comprehensive dementia care in traditional Medicare, especially in underserved communities.5. Develop mechanisms to pay community‐based organizations (CBOs) for services provided to individuals living with dementia and their caregivers.ConclusionAlternative payment models are needed under traditional Medicare to incentivize providers to coordinate care, pay CBOs for the services they provide, align incentives among payers, providers, and patients, and ensure those living with dementia and their caregivers receive more seamless, coordinated health‐ and long‐term care.
Distinct features of rapidly progressive Alzheimer’s disease
Authors: Wang Ping , Lynn Audrey , Song Yeunjoo E. , Haines Jonathan L. 
Published: December 2022

AbstractBackgroundRapidly progressive Alzheimer’s disease (rpAD) has been recognized as a subtype of Late‐Onset Alzheimer’s disease (LOAD) characterized by accelerated cognitive decline and/or reduced survival. The cause of variable progression rates of AD is largely unknown, and information regarding unique clinical features of rpAD is limited in longitudinal cohorts.MethodA retrospective analysis was performed on AD patients in the National Alzheimer’s Coordinating Center (NACC) database from 2015 to 2021. Patients with rpAD were identified by reduced survival time (time from symptom onset to death < = three years) or accelerated cognition decline (defined as Mini‐Mental State Exam [MMSE] decrease > = 6 points/year or Clinical Dementia Rating scale [CDR] global score increase to 2 or 3 within three years). Demographic, clinical, and neuropsychological measurements were compared between patients with rpAD, typical “slow” progressive AD, and normal controls. rpAD patients and normal controls with Whole Genome Sequencing (WGS) data available from the Alzheimer’s Disease Sequencing Project (ADSP) were selected for a pilot genome‐wide association study (GWAS).ResultAmong 43,746 NACC participants, 983 patients met our criteria for rpAD. rpAD patients had a mean survival of 2.8±0.5 years and their decline in MMSE was 6.4±5.9 points/year. Compared to controls, rpAD patients were older (72.6±8.6 vs 70.0±8.6, p < 0.001), more likely to be male (39% vs 33%, p < 0.001) and had fewer years of education (14.6±3.6 vs 15.9±3.0, p < 0.001). Compared to AD patients who progressed slowly, rpAD patients showed a more rapid decline in neuropsychological tests measuring working memory, language, attention, and executive function (p values < 0.001). GWAS was performed on 175 rpAD patients and 525 age‐ and sex‐matched NACC controls. 49 genetic variants showed significant associations with rpAD (p‐values < 1 × 10−5).ConclusionIn the longitudinal NACC cohort, rapidly progressive AD constitutes an important subset, featuring a short survival with rapid decline of cognitive and neuropsychological functions. Previously known genetic risk variants for AD were not found in this rpAD cohort. Further examination of rpAD cohort could help identify unique mechanisms that drive the rate progression in AD for different groups of patients.
Clinical and sociodemographic characteristics of patients with Neurocognitive Disorder (NCD) (dementia) at the Ramón de la Fuente Muñiz National Institute of Psychiatry (INPRFM) Psychogeriatrics Clinic in Mexico City, between 2011 and 2020.
Authors: Marin Luis Fernando Collazos , Lopez Guillermo Velazquez , Salas Ismael Aguilar 
Published: December 2022

AbstractBackgroundThe demographic and epidemiological transition, increased life expectancy and decreased fertility rate have increased the prevalence of dementia that affects 55 million people worldwide; it is estimated to affect 75 million by 2030 and increase three times by 2050. The clinical and sociodemographic characteristics of the studied population are unknown. It is the first study of its kind in the region. It’s also an unaddressed issue where an exploratory type protocol was carried out and a hypothesis was not formulated.MethodsDescriptive, observational, cross‐sectional, retrospective study. A Mexican population database including subjects from a previous work was created and then a secondary analysis was made. Every patient diagnosed with NCD was included regardless of age and with a clinical, psychiatric and/or geriatric syndrome diagnosis. No instrument or scale was used. There was no funding. Statistical analysis was done in SPSS 20.0.Results2056 records were found, 675 met the inclusion criteria. Age 74.71 (±9.02) years, from the urban area 93.78% (n = 633), women 72.15% (n = 487), primary school 49.90% (n = 243), widows 37.99% (n = 185), household occupation 77.21% (n = 376), low socioeconomic status 57.08% (n = 278). 59.86% (n = 404) had a major NCD, MMSE of 18.88 points (±6.68), Alzheimer’s disease was present in 31.56% (n = 213) both in those under 60 years of age 25.64% (n = 10) and in those older than 60 years old 31.92% (n = 203). Mild NCD was present in 9.19% (n = 62), the diagnosis was ruled out in 3.11% (n = 21) and a diagnosis could not be concluded in 25.93% (175). The most common psychiatric pathologies were Depressive and anxious disorder with 80.00% (n = 540) and 9.19% (n = 62) respectively; Clinical diagnosis were Arterial Hypertension 50.07% (n = 338), diabetes mellitus 22.22% (n = 150) and geriatric syndromes in 14.57% (n = 218).ConclusionThe study analyzes the characteristics of the clinic’s patients. The first of its kind which differentiates it from population based studies. The results are not intended to be extrapolated to the general population. Due to limitations in the diagnostic process of dementias, there were no diagnostic methods such as biomarkers in cerebrospinal fluid, functional or genetic neuroimaging. The intention is to promote dementia research and highlight the extent of the problem to Latinamerican Governments.
Trajectories of cognitive performance in late middle‐aged adults: Bayesian random change point mixed model analysis in WRAP
Authors: Du Lianlian , Koscik Rebecca Langhough , Betthauser Tobey J , Jonaitis Erin M. , Hermann Bruce P , Johnson Sterling C. , Larget Bret , Chappell Richard J. 
Published: December 2022

AbstractBackgroundPrevious studies indicate that rates of cognitive decline in Alzheimer’s disease (AD) and other dementias may accelerate significantly as brain pathology increases. The objectives of this study included to: 1) characterize changepoints and related slope parameters across four cognitive composites in a longitudinal cohort study; and 2) examine how these parameters varied across predictors of interest.MethodsDementia‐free participants at baseline from the Wisconsin Registry for Alzheimer’s Prevention (WRAP) with > = 3 cognitive assessments were eligible (n≈1071; mean(sd) baseline age = 58.4(6.4)). We used newly‐developed Bayesian random change point mixed models (BRCPMM) to estimate fixed (group‐level) and random (person‐level) change points (CPs), slopes pre‐ and post‐CP, and intercepts at CP for four cognitive composites: three‐test preclinical Alzheimer’s cognitive composite (PACC3; primary outcome), immediate learning, delayed learning, and executive function. We used non‐parametric statistics to test whether PACC3 estimates differed by: last cognitive status observed (cognitively unimpaired‐stable or ‐declining (CU‐S, CU‐D), MCI, and dementia); sex/gender, and APOE‐e4 carrier status.ResultsPosterior median fixed and random effect estimates (corresponding 95% credible intervals from 20000 BRCPMM runs) are summarized in Table 1 by outcome. The PACC3 group‐level CP was earliest at ∼75.56 [72.98,78.44] years old with 95% of individuals hitting CP between 59.69 and 91.86. Timing of CP was significantly associated with last observed cognitive status (Table 2); those 37 (3.46%) progressing to MCI/dementia had estimated CP’s before or during study participation while those remaining unimpaired had estimated CP’s after their last visit. All random effects (person‐level) PACC3 estimates differed by worst cognitive status (Figure_1) and sex/gender (Figure_2). For example, while the CU‐D and MCI groups had similar slopes before CP, CP occurred earlier, estimated PACC3 at CP was lower, and post‐CP slope was worse in the MCI group compared to CU‐D (Figure_1). APOE‐e4 random‐effects estimates differed by CP and post‐CP slopes (Figure 3).ConclusionsThe timing and rates of change in different cognitive composites differ by cognitive status, gender, and APOE‐e4 status. Predicting individual cognition trajectories and change points may provide an opportunity for early intervention by diagnosing high‐risk subjects at the right time for treatment and/or enrollment in a clinical trial.
Cognitive Reserve in Mild Cognitive Impairment: structural and functional imaging correlates
Authors: Carbone Chiara , Balboni Erica , Beltrami Daniela , Gasparini Federico , Fiondella Luigi , Salemme Simone , Vinceti Giulia , Molinari Maria Angela , Marti Alessandro , Tondelli Manuela , Chiari Annalisa , Zamboni Giovanna 
Published: December 2022

AbstractBackgroundThe term “Cognitive Reserve” (CR) refers to the ability of the brain to cope with the damage in order to minimize symptomatology. Several studies have shown controversial data about functional and structural correlates of CR in normal and pathological aging, probably due to the use of different CR proxies (level of education, occupational complexity, participation in leisure activities, IQ, verbal abilities or intelligence, heterogeneous fMRI tasks). The aim of this study was to investigate imaging correlates of different aspects of CR in a sample of patients with Mild Cognitive Impairment (MCI).MethodPatients with a diagnosis of MCI and young onset of cognitive symptoms (< 65) answered the Cognitive Reserve Index questionnaire (CRIq) aimed at measuring cognitive reserve acquired during lifetime. Patients also underwent multimodal Magnetic Resonance Imaging (MRI) on a 3T scanner including high‐resolution T1 and functional MRI sequences acquired at rest (resting fMRI). CRIq‐Total score and single subscores (CRIq‐Education, ‐WorkingActivity and ‐LeisureTime) were related to regional grey matter (GM) volume, whole brain fractional anisotropy (FA) and functional connectivity of resting‐state networks (RSNs) using, respectively, Voxel Based Morphometry (VBM), Tract‐Based Spatial Statistics (TBSS), and independent component analysis of resting fMRI (MELODIC).ResultThirty‐nine patients were recruited. The median CRIq‐Total, ‐Education, ‐WorkingActivity and ‐LeisureTime scores were respectively 102, 97, 105 and 105. VBM correlational analysis showed no significant results. TBSS revealed a negative correlation between CRIq‐LeisureTime and FA of the body of corpus callosum. Resting‐fMRI analyses revealed negative correlations between CRIq scores and functional connectivity, involving particularly frontal and temporal areas.ConclusionIn patients with MCI, cognitive reserve relates to functional connectivity of fronto‐temporal areas rather than to structural variability (grey matter atrophy or white matter microstructural integrity). The negative correlations found between functional connectivity and CRIq scores shows that patients with high cognitive reserve may not need to increase functional connectivity.
Role strain and COVID‐era burden among South Asian caregivers of individuals with brain health conditions and disabilities
Authors: Tjin Anna , Troy Carol , Vinarti Retno Aulia , Banerjee Debanjan , Goodwin Anna , Yeo Selvie , Saha Sanjib , KRISHNA Murali , Goswami S P , Chen Yaohua Sophie , Leroi Iracema , O'Sullivan Roger 
Published: December 2022

AbstractBackgroundThe COVID‐19 pandemic has renewed attention to the conflicting demands placed on caregivers worldwide. Nowhere is this more evident than in South Asia, where cultural norms and a scarcity of long‐term care facilities have made the home the locus of caregiving for individuals with brain health conditions and disabilities. A hidden cost of this informal arrangement is the burden experienced by the primary caregiver. This may be exacerbated when traditional caregiving expectations clash with personal aspirations outside the family.MethodThis paper investigates the determinants of burden among 494 informal caregivers in India, Pakistan, and Bangladesh during the COVID‐19 pandemic. The variables, obtained from the Coping with Loneliness, Isolation, and COVID‐19 (CLIC) Global Caregiver study, include caregiver demographic characteristics, features of the caregiving arrangement, and subjective measures of the caregiving experience. The dependent variable in our analysis, the perceived frequency of burden, is rated by respondents on a five‐level scale. Role strain is expected to be greatest among young, educated women living with the care recipient in their own homes. Therefore, burden should exhibit a positive association with female gender, education, and cohabitation, and a negative association with age.ResultOut of the 494 caregivers included in the study, 33.8% experienced increasing burden and 58% experienced loneliness some of the time during Covid‐19. The ordinal logistic marginal effects are consistent with all four hypotheses. Caregiver Burden is found to be positively correlated with female gender (OR,1.92; 95%CI, 0.35,1,03; P=<0.001), the 18‐39 age range (OR,1.71; 95%CI, 0.114, 0,963; P=0.01), poor finances (OR,2.192; 95%CI,0.22,1.34; P=0.006), poor physical health (OR, 2.24, 95%CI, 0.29,1.32, P=0.002), poor mental health (OR,1.86; 95%CI, 0.14,1.10, P=0.011), and care recipients with dementia/Alzheimer's (OR,2.76; 95%CI, 0.52,1.51, P=<0.001) and/or mental health conditions (OR,1.61; 95%CI, 0.02,0.94, P=0.039).ConclusionRole strain may be a significant driver of burden when the caretaker’s educational and professional potential collide with traditional South Asian family obligations. The burden reported by our respondents suggests that role strain may elevate stress among young, educated caregivers. Our results, therefore, provide indirect evidence concerning the changing economic and socio‐cultural context of caregiving in South Asian households.