bluuebunny/crossref_metadata_2025_split huggingface dataset:
Applied co‐creation approach to the design and development of a socially assistive robot system to support hardware and software accessibility and acceptability needs of individuals with AD/ADRD and their caregivers
Authors: Kingsley Caroline , Stout Andrew , Herrera Nicolas , Mittelman Mary S , Niehaus James 
Published: December 2020

AbstractBackgroundCommercially available socially‐assistive robots (SARs) serve as a promising new assistive technology platform for individuals with early and middle stage AD/ADRD and their caregivers, yet often fail to address the specific usability, accessibility, and acceptability needs of these user groups. Loneliness, social isolation, depression, anxiety, and overall diminished quality of life are symptoms that individuals with AD/ADRD and their caregivers often share. The emerging market of SARs brings an advantage over existing assistive technologies because they provide an opportunity for technology to empathetically and seamlessly provide affordable and scalable solutions to social isolation and loneliness that are often left unaddressed.MethodThree rounds of co‐creation sessions, consisting of interviews with individuals with early and middle stage AD/ADRD and focus groups with AD/ADRD caregivers, to understand both groups' pain points, needs, methods/frequency of social interaction, experiences with technology, criteria for building trust in technology/systems, perception/opinions of SARs, and interest in and ideas for ways SARs can improve their daily lives, to drive co‐development of hardware and software solutions to adapt commercially available SARs to deliver useful experiences tuned to population‐specific requirements.ResultWe will present on the qualitative methods, analysis, and findings from our NIA‐funded IRB‐approved co‐creation user research and demonstrate our resultant prototype system, involving a commercial social robot with user‐centered software and hardware adaptations for increased accessibility and usability (e.g., large tactile buttons, large visual display, additional speakers and microphones). Additionally, we will discuss lessons learned from our co‐creation user research approach in the context of addressing two unique populations and recommendations for future approaches.ConclusionIndividuals with early and middle stage AD/ADRD and their caregivers are generally receptive and excited by the potential for social robot technology and can greatly benefit from it when designed thoughtfully and inclusively. Current SARs provide promise, but must be adapted to the specific interaction needs of these populations to increase adoption and utility. An iterative, co‐creation user research and design process involving both individuals with AD/ADRD and their caregivers provides a promising approach to develop useful and acceptable in‐home social robot technology to enhance the social connectedness, well‐being, and quality of life of these populations.
Developing appropriate methodologies for effective clinical trial engagement in vascular cognitive impairment and dementia (VCID)
Authors: Schneider Lon 
Published: December 2020

AbstractBackgroundCompared with the substantial advances in Alzheimer’s trials and methods, there have been only attenuated advances in trials for vascular cognitive impairment and dementia (VCID). From a broad perspective, a clinicaltrials.gov search yielded 621 clinical trials in Alzheimer’s, but only 75 interventional trials that included patients with vascular dementia of which 35 also included patients with a variety of dementias; and the interventions for the majority of the trials were not focused on cognitive or functional outcomes. Currently, there are no drugs with FDA marketing approval specifically for VCID.MethodQualitative and quantitative assessment of trials for VCI from the 1970s onward was undertaken to assess the evolution of drug development and trials. Diagnoses, drug interventions, targets, the use of biomarkers, and trials methods were examined in order to assess the current state and barriers to drug development for vascular brain injury.ResultPreliminary assessment reveals that various diagnostic criteria, interventions, and inconsistent trials methods have been employed. It is often unclear how participants were identified or diagnosed. Sample sizes tend to be small, and outcomes various. The rationales for specific treatments are often not apparent. Mainly trials rely on a post‐stroke, multi‐infarct dependent diagnosis; a minority on a small vessel, ischemia‐based definition. In many diagnostic criteria are vague. Notable groupings include cholinesterase inhibitors and cerebral amyloid angiopathy. Most of the former group relied on NINCDS‐AIREN criteria, Alzheimer trials methods, and were intended for FDA regulatory consideration. No trial seemed to use vascular biomarkers or validated drug targets.ConclusionThe lack of progress in VCID trials is intriguing considering its high prevalence and overlap with Alzheimer pathology. The various VCID diagnoses and conditions and their heterogeneity represents barriers to treatment development. As evidence is substantial that VCID is at least a modifier of Alzheimer pathology and expression, the development of valid drug targets, biomarkers, drugs, and regulatory pathways are essential. Noteworthy is a focus developing biomarkers for small vessel disease (Greenberg SM, et al https://markvcid.partners.org/). Despite the challenges, the field needs to move in a way that will engage regulatory agencies and pharma to develop pathways and therapeutic pipelines.
Epidemiology informs randomized clinical trials of cognitive impairment and late‐onset, sporadic dementias
Authors: Gustafson Deborah R. 
Published: December 2020

AbstractBackgroundDespite strong and consistent evidence, criticisms of epidemiologic associations between vascular factors and cognitive impairments (CI) and late‐onset, sporadic Alzheimer’s Disease (LOAD), abound. A common critique is, “If vascular risk factors identified in observational epidemiology are real, why do clinical trials of treatments for vascular risk fail to improve cognition or prevent LOAD?’ Given the strengths of Dementia Epidemiology in identifying population‐level questions and solutions, how can there be a better translation to Randomized Controlled Trials (RCT)?MethodHerein, it is proposed that greater attention to ‘real world’ epidemiology and ‘fit for purpose and fit for community’ approaches, can result in better planning of RCT. Facets of accomplishing this include the following considerations: 1) CI and LOAD result from exposures occurring over the life course; 2) definitions and terminology related to exposures and clinical outcomes; 3) characteristics of populations at risk and their variation over the life course, e.g., mid‐life to late‐life; 4) attaining data on latest life exposures and flux; 5) duration of exposure(s), such as medication adherence, that are required to achieve desired effects; 6) reverse causality; 7) birth cohort; 8) multimorbidities; and 9) genetic susceptibility.ResultTwo practical examples translating the observational epidemiology to the RCT will be provided. Both examples involve obesity as the exposure, and the outcomes include ADRD and Vascular Cognitive Impairment (VCI).ConclusionRCT must embrace more of the chaos (intra‐ and inter‐individual and ‐community variabilities) to better identify prevention strategies that work. This proposed presentation will address concerns that provide a natural segue for the scientific community to focus on, facilitate and feed forward future solutions and fill knowledge gaps.
Divergent effects of education and occupation history on age at onset within Alzheimer’s and frontotemporal dementia
Authors: Miller Zachary A. , Allen Isabel Elaine , Neylan Kyra D. , Diggs Ryan T. , Bogely Rian L. , Palser Eleanor , Perry David C. , Brown Jesse , Sturm Virginia , Rabinovici Gil D. , Rosen Howard J. , Kramer Joel H. , Rankin Katherine , Grinberg Lea Tenenholz , Seeley William W. , Gorno‐Tempini Marilu , Miller Bruce L. 
Published: December 2020

AbstractBackgroundCognitive reserve refers to the resilience education and life‐time mental activity confer against neurodegenerative disease. Mostly understood within Alzheimer’s disease (AD), we investigated the impact education and occupation history have within frontotemporal dementia (FTD).MethodsEmploying the United States Bureau of Labor Statistics (USBLS) job classification, we screened occupation histories in all participants who presented to the UCSF MAC from 1998‐2019 and met criteria for FTD (n=638; including behavioral variant FTD, semantic variant primary progressive aphasia, and nonfluent variant primary progressive aphasia) and compared to a sample of AD matched for age at symptom onset (n=600).ResultsCompared to AD, FTD possessed significantly higher amounts of years of education (15.7±2.9 vs. 15.3±3.5, p=0.03) and male sex (50.2% vs. 43.7%, p=0.02). Adjusting for these differences, seven of 23 USBLS categories differed between AD and FTD (Table 1). “Architecture & Engineering,” “Computer & Mathematical,” and “Life, Physical, & Social Science,” which together constitute the STEM (Science, Technology, Engineering, and Mathematics) professions, were increased in FTD. “Arts, Design, Entertainment, Sports, & Media,” “Personal Care & Services,” “Production,” and “Other” occupation categories were increased in AD (referred to here as AD‐Relevant). STEM occupations predict FTD over AD (OR, 2.3; 95% CI, 1.7 to 3.2), whereas AD‐Relevant occupations predict AD over FTD (OR, 2.2; 95% CI, 1.6 to 3.1). Survival curve analyses of STEM vs. AD‐Relevant vs. all remaining occupations revealed that STEM occupation associates with earlier symptom onset in FTD and later onset in AD and AD‐Relevant careers, the opposite. Furthermore, within FTD, disease duration was longest in the STEM cohort compared to all remaining and AD‐relevant careers (11.4 vs. 8.9 vs. 9.3, p=0.003).ConclusionsWe find that education and occupation history impact age at symptom onset within AD and FTD, in opposing manner. The cognitive reserve hypothesis was created to explain the delayed symptom onset and shortened disease duration increased years of education and occupational complexity bestow on individuals with AD. Within FTD, we observe the opposite ‐ earlier symptom onset and greater disease duration in STEM professionals ‐ suggesting a reciprocal process may be at work within FTD.
Subject selection and identification of optimal clinical outcome measures in dementia trials focused on vascular cognitive impairment and dementia
Authors: Peters Ruth 
Published: December 2020

AbstractBackgroundResearch into the understanding and identification of modifiable clinical and lifestyle related factors associated with increased risk of dementia has grown enormously over the past twenty years. The development of the field is now such that we have a general awareness of the main risk factors, and, in many areas, public health messaging is underway to support risk reduction. Given the overlap between the risk factors for dementia and those for other non‐communicable disease, for example, cardiovascular disease and cancer, the potential benefit of risk reduction activities is unequivocal. Despite this, the evidence base for dementia risk reduction is not strong and for several risk factors the clinical trial results have been mixed and inconclusive.MethodTo evaluate reasons for the inconsistency between the epidemiology and the clinical trial evidence we selected key modifiable risk factors that lend themselves to blinded pharmacological intervention and where trial results are available. E.g. antihypertensives, hormone replacement therapy, non‐steroidal anti‐inflammatories, statins and omega 3 supplementation. Experts in the field of dementia risk factor epidemiology, dementia risk reduction trials, and with statistical and clinical, Alzheimer’s and vascular dementia expertise were convened to critically appraise the evidence.ResultExplanations for the discrepancies arise in both the trial and epidemiology evidence. E.g.; selection of trial populations from age or population groups that do not match the groups where the association between the risk factor and dementia outcome is strongest, a lack of understanding of the most appropriate dose of intervention or goal level of risk factor for the best cognitive outcome and the short duration of trials in the context of a disease process with a decades long prodromal phase. Conversely epidemiology that suffers from confounding by indication or that fails to fully account for confounding by key factors such as socioeconomic status, or to take account of the life‐course.ConclusionTo fully understand the potential for risk reduction and to target resources accordingly will require both a new and more sophisticated evaluation of existing data and the delivery of new and better designed trials. Recommendations are made for the next steps.
Association between race/ethnicity and neuroimaging biomarkers in middle‐ and older‐aged adults
Authors: Turney Indira C , Lao Patrick J , Rentería Miguel Arce , Laing Krystal K , Beato Juliet M , Chesebro Anthony G , Amarante Erica , Igwe Kay C , Schupf Nicole , Mayeux Richard , Manly Jennifer J , Brickman Adam M 
Published: December 2020

AbstractBackgroundAlzheimer’s disease and related disorders (ADRD) disproportionately affect African American, Hispanic, and American Indian older adults. Previous studies report racial/ethnic differences in markers of aging and neurodegeneration, but results are inconsistent due to small, non‐representative samples. We hypothesized that accelerated aging would manifest as a stronger negative relationship between age and MRI biomarkers among community‐dwelling racial/ethnic minorities compared with non‐Hispanic Whites.MethodADRD‐related neuroimaging measures of composite cortical thickness (CT) in AD signature regions and white matter hyperintensity (WMH) volume were assessed in White (n=274), Black (n=451), and Hispanic (n=663) participants from community‐based, intergenerational studies of cognitive aging and dementia. WHICAP participants are Medicare‐eligible participants aged 65 and older. The Offspring cohort includes middle‐aged children of the WHICAP study participants (of the 1482 participants, 1209 families were represented). We examined the association of cohort age and race/ethnicity with each imaging marker, after adjusting for sex/gender and family relatedness, and tested interactions between cohort age and race/ethnicity in separate models.ResultWHICAP participants were 75±6.5 years old and Offspring participants were 55±10.5 years old at time of MRI. As expected, WHICAP participants had lower CT in AD signature regions than Offspring (β=‐.06,95%CI:‐.05,‐.08). Compared with Whites, Blacks and Hispanics had lower CT in AD signature regions, but an interaction between cohort age and race/ethnicity revealed that older Blacks had disproportionately thinner CT in AD signature regions (β=‐.05,95%CI:‐.01,‐.10). Offspring participants had lower WMH volume than WHICAP participants (β=‐1.4,95%CI:‐2.1,‐.58). Blacks had more WMH burden overall (β=1.04,95%CI:.13,2.0), but there were no interactions between race/ethnicity and cohort age on WMH burden.ConclusionAmong diverse, community‐based participants, there are disparities in markers of brain atrophy in both cohorts but this effect is intensified with age, where older Blacks show disproportionately greater brain atrophy compared with other groups. Disparities in small vessel cerebrovascular disease are apparent in middle‐age and late‐life, but this effect is similar across age‐groups. Results suggest that racial/ethnic disparities in markers of brain aging and disease are apparent even in middle‐age and, in the case of neurodegeneration, may amplify with increasing age. These differences may be due to accelerated aging secondary to sociocultural factors and experiences.
Forecasts for numbers of people living with dementia to 2050 and estimates for impact of smoking cessation: A modelling study in four European countries
Authors: Ahmadi‐Abhari Sara , Bandosz Piotr , Shipley Martin J , Whittaker Hannah , Middleton Lefkos T , Kivipelto Miia , Brunner Eric , Kivimaki Mika 
Published: December 2020

AbstractBackgroundForecasting dementia prevalence and the impact of preventive lifestyle interventions, requires accounting for the reduced risk of dementia and cardiovascular disease (CVD) and the concurrent increase in life‐expectancy and growing population susceptible to dementia. We aimed to forecast prevalence of dementia in Sweden, Spain, France and Poland in 2020 and 2050 assuming calendar trends in mortality rates and incidence of dementia and CVD continue the trajectories observed over the past two decades, and to estimate change in this number if elimination of cigarette‐smoking was successful.MethodWe developed a Monte‐Carlo Markov model with data derived from official statistics for population numbers and mortality rates and the Survey for Health, Ageing and Retirement in Europe for baseline prevalence estimates and transition probabilities. All input parameters were age‐ and sex‐specific and were projected to the future based on observed calendar trends. Relative risks of CVD, dementia, and mortality for smoking, obtained from meta‐analyses of published studies, were used to modify transition probabilities proportionate to the change in population attributable risk fractions if smoking is eliminated by 2025.ResultLife‐expectancy at age 50 in Sweden was estimated at 31.1 years in 2020, increasing to 35.3 by 2050 if observed trajectories continue, and at 36.1 if smoking elimination was successful (Figure). Corresponding figures were 32.6, 41.7, and 44.0 years respectively for Spain; 32.5, 38.7, and 40.7 for France; and 30.3, 37.8, and 39.9 for Poland. Estimated numbers of people living with dementia in 2020 and 2050, and estimated numbers by 2050 if smoking was eliminated were 147,000 (age‐standardized prevalence 4.2%), 223,000 (4.1%) and 239,000 (4.2%) respectively in Sweden (Table); 1,090,000 (6.8%), 2,913,000 (6.4%) and 3,194,000 (6.6%) in Spain; 998,000 (4.8%), 2,128,000 (4.3%) and 2,400,000 (4.2%) in France; and 623,000 (3.9%), 1,254,000 (3.5%) and 1,442,000 (3.5%) in Poland.ConclusionSubstantial increases in numbers with dementia by 2050 emphasize the importance of planning public health policies that meet the growing health‐ and social‐care needs of dementia patients in the next three‐decades. Although smoking cessation increases dementia‐free life‐years, it is unlikely to halt the increase in the numbers of dementia patients that result from concurrent increases in life‐expectancy.
Potentially inappropriate medications that impact cognition are common in older adults with Alzheimer’s disease or related dementias, driven by antipsychotics
Authors: Vickers Lauren , Martinez Ashley I , Wallem Alexandra M , Moga Daniela C 
Published: December 2020

AbstractBackgroundOlder adults with dementia are particularly vulnerable to adverse effects of potentially inappropriate medication (PIM) use. The Beers Criteria identifies PIMs, including antipsychotics, benzodiazepines (BZD), and non‐benzodiazepine benzodiazepine receptor agonist hypnotics (Z drugs) that are linked to cognitive impairment or decline (“Cog‐PIMs”). This study investigated the difference in Cog‐PIM use as reported for patients with and without Alzheimer’s disease or related dementias (ADRD) in a nationally representative sample of the United States population.MethodsWe conducted a cross‐sectional study using the 2016 National Ambulatory Medical Care Survey. The analysis included non‐perioperative office‐based visits for patients ≥ 65 years old. Visit characteristics were compared between those with and without ADRD using descriptive statistics, and adjusted logistic regression was used to identify predictors of Cog‐PIM use.ResultsOf the 218,182,131 outpatient visits, 2.2% were for patients with ADRD (N=4,651,563). Approximately twice as many visits with Cog‐PIM reports were among those with ADRD compared to those without (22.9 vs 10.7%), after adjusting for known confounders, ADRD was not a significant predictor of Cog‐PIM report (OR [95% CI] 1.2 [0.4‐3.3]). This is likely because there were no differences between groups in report of BZDs (8.7 vs 8.8%) and Z drugs (2.2 vs 1.9%). The most striking difference in Cog‐PIM report between those with and without ADRD occurred with antipsychotics, which were noted in 15.5% vs 0.8% of visits; the most common included quetiapine (40.0%), haloperidol (26.2%), and olanzapine (20.3%). After adjusting for potential confounders, ADRD was a significant predictor of antipsychotic report (aOR [95% CI] 34.9 [8.7‐141.1]). Hispanic ethnicity and report of >5 medications were also significantly associated with antipsychotic use (4.3 [1.4‐13.4] and 6.3 [1.9‐20.7] respectively).ConclusionIn a nationally representative sample, Cog‐PIM use was reported in nearly one‐quarter of visits for patients with ADRD, driven by report of an antipsychotic. Presence of ADRD was a significant predictor of visits reporting an antipsychotic, and both traditional and atypical antipsychotics were highly prevalent. Given that these medications are not recommended for older adults and that they may negatively impact cognition, future work should investigate points of intervention to reduce Cog‐PIM use (specifically antipsychotics) in the ADRD population.
Peripheral neurofilament light (NFL) chain level predicts the two‐year outcome of amnestic mild cognitive impairment in Chinese Han population
Authors: Zhao Qianhua , Ding Ding 
Published: December 2020

AbstractBackgroundBiomarkers that could track disease onset and progression in patients with mild cognitive impairment (MCI). We investigate whether peripheral neurofilament light (NfL) concentration is associated with clinical outcome in a MCI cohort.MethodA cohort of 401 patients with aMCI underwent annually longitudinal clinical follow‐up and neuropsychological testing. Plasma level of NFL, Abeta40, Abeta42, total Tau were assessed using an ultrasensitive immunoassay on the Single molecule array (Simoa) platform.ResultPlasma markers samples were analyzed for Tau, Abeta 40/42 and NFL; data assessed as predictors of conversions from MCI to dementia. Among all the patients, 258 finished two‐year annually follow‐up. Of which, 80 (31.0%) converted to dementia, 129 (50.0%) remained to be MCI , 49 (19.0%) reversed to cognitively normal. Plasma NFL levels were elevated in conversion group compared to non‐conversion group. Elevated plasma NFL showed strong association with the cognitive decline, after adjusting for age, sex, and comorbid diseases. Plasma Abeta40/42 ratio also showed a trend to discriminate converter out of MCI patients, but didn’t reach statistical significance.ConclusionElevated baseline plasma NFL level was associated with greater rate of cognitive decline in MCI patients, and with the conversion from MCI to dementia in Chinese population.