bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of anxiety with vascular risk factors in memory clinic patients with MCI and Alzheimer’s dementia
Authors: Razavian Narges , Dodson John , Horwitz Leora , Aphinyanaphongs Yindalon , Wisniewski Thomas , Masurkar Arjun V 
Published: December 2021

AbstractBackgroundAnxiety is increasingly recognized as an early neuropsychiatric symptom in Alzheimer’s disease (AD) that portends faster progression. The etiology of anxiety in AD and the mechanism of this faster progression are unclear. Vascular risk factors independently associate with anxiety and dementia, and thus may play an important role in AD‐related anxiety. We aimed to study the prevalence of vascular risk factors in memory clinic patients with and without anxiety at the mild cognitive impairment (MCI) and AD dementia stages.MethodThe cohort included patients aged ≥ 65 years who were evaluated at the NYU Langone Barlow Center for Memory Evaluation and Treatment between January 1, 2015 and June 24, 2019. Analysis was limited to patients who received a diagnosis of mild cognitive impairment (MCI) or Alzheimer’s dementia (AD). At each stage, the cohort was divided into those with and without a coded diagnosis related to anxiety. Outcomes and clinical variables were based on electronic health records. Definitions for AD, MCI, anxiety, and vascular risk factors are shown in Tables 1‐2.Result2046 and 1594 patients were included in the MCI and AD cohorts, with anxiety prevalence of 26% and 20% in each cohort respectively. Characteristics of MCI and AD patients with and without anxiety are reported in Table 3. The rates of key cardio‐ and cerebrovascular risk factors were of increased frequency in anxious vs. non‐anxious patients in both MCI and AD cohorts: hypertension, hyperlipidemia, myocardial infarction, atrial fibrillation, ischemic heart disease, heart failure, and diabetes mellitus. Moreover, these differences were amplified in the dementia stage compared to the MCI stage. Peripheral vascular disease, stroke, and sleep apnea differences were unique to the dementia stage.ConclusionThese results suggest that vascular risk factors could play a critical role in the relationship between anxiety and AD. This relationship strengthens as AD progresses from prodromal to dementia stage, and also involves additional factors. Further characterization of these relationships and their mechanisms may uncover novel pathways to manage AD‐related neuropsychiatric symptoms and modify AD progression.
Accounting for practice effects improves stability of MCI diagnosis and uncovers new impairments
Authors: Sanderson‐Cimino Mark E. , Elman Jeremy A. , Tu Xin M , Panizzon Matthew S. , Jak Amy J. , Franz Carol E. , Kremen William S. 
Published: December 2021

AbstractBackgroundWe previously showed that failure to account for practice effects (PEs) delays detection of conversion from unimpaired to mild cognitive impairment (MCI) and reduces diagnostic accuracy based on biomarker positivity data. Even among those who decline, PE can mask steeper declines by inflating cognitive scores. Within MCI samples, PEs may increase reversion rates and impede detection of new impairments. Here, within a baseline MCI sample, we evaluated how PEs affect prevalence, reversion rates, and progression from single‐domain to multi‐domain MCI at follow‐up.MethodWe examined 347 baseline Alzheimer’s Disease Neuroimaging Initiative MCI participants (mean age=73.2; SD=7.4). We used Jak/Bondi diagnostic criteria (6 tests). We also calculated PEs on a cognitive composite (ADAS‐cog 11) and a cognitive screener (MMSE). We identified participants who were demographically matched to returning subjects at their 1‐year follow‐up. The only difference was that one group was tested once and the other had completed prior testing. We subtracted PEs—based on comparing these groups—from follow‐up scores and recalculated MCI diagnoses.ResultPEs were absent or small for 5 tests (Cohen’s d=.00‐.06) and medium for 1 (d=.50). There was a PE on the MMSE (Cohen’s d =.16), but none was found on the ADAS‐cog 11. Accounting for PEs increased MCI prevalence at follow‐up by 6% (252 vs 268), and reduced reversion rate by 15% (95 vs 79). PEs also masked progression from single‐domain to multi‐domain MCI: 24 vs 36 (+50.0% after accounting for PEs).ConclusionAlthough PEs were small, accounting for them in baseline MCI participants after 1‐year, increased MCI prevalence and progression from single‐domain to multi‐domain, and decreased reversion rates. PEs may be masked within a composite measures, but were present on a short cognitive screener. Failure to consider PEs reduces accuracy regarding conclusions about MCI stability/change and weakens our ability to determine when impairment spreads to new domains.
Towards a brain health diplomacy toolkit: Supporting tomorrow's brain health leaders
Authors: Dawson Walter D , Eyre Harris A 
Published: December 2021

AbstractBackgroundThe complex factors that may affect brain health at an individual, community, national, and international level require large‐scale diplomatic efforts to improve outcomes across the globe. Brain health diplomacy has recently been proposed as a framework to support the aim of mitigating threats to brain health with a specific focus on advanced age. Providing emerging brain health leaders with the tools to practice diplomacy is an important component of the framework and is essential to the ambitious goal of reducing the global burden of Alzheimer's disease and related dementias (ADRD).MethodDrawing on several existing toolkits that support diplomacy, we propose the development of a toolkit for brain health leaders to advance brain health diplomacy across disciplines, sectors, and nations.ResultPredicates for the brain health diplomacy toolkit include science diplomacy (American Academy for the Advancement of Science and European Science Diplomacy Cluster), innovation diplomacy (Nesta and Danish Government's TechPlomat), general diplomacy (Academy of Diplomacy, and the concept of health attaches (World Health Organization and United Nations).ConclusionThe brain health diplomacy toolkit offers a practical set of tools for brain health leaders to enhance international efforts to reduce ADRD.
Health care professionals and use of digital technologies in patients with dementia and related disorders
Authors: Andrade Alan Cronemberger , Corrado Marta , Bertolucci Paulo Henrique Ferreira 
Published: December 2021

AbstractBackgroundDigital technologies (digiTech) enhance benefits in healthcare and are present in elderly people lives. Healthcare professionals (HCP) who deal with dementia and related disorders face enormous challenges in delivering healthcare using digital devices, and Covid‐19 pandemic showed these pitfalls should be addressed. Technology solutions in elder people are being developed, not every HCP is heard, and we lack information about what these professionals think about this.MethodsUsing structured questionnaires and asynchronous electrotonic data capture, we asked experienced (84.3% postgraduate degrees) HCP with different backgrounds (8 practice areas) about what they think of technology use among their patients and carers. The average person in our sample (N = 51) was a highly skilled (22.2 study‐years) female (70.6%) medical doctor (62.8%) aged 39.1 years old (27 to 77 years), highly exposed to digiTech (68.6% mobile devices usage ≥4 hours/day). Neurologists (37.3%), neuropsychologists (15.7%), psychiatrists (13.7%), geriatricians (11.8%) were the most represented groups. This observational cross‐sectional study is part of a Brazilian pilot study to explore technology usage in higher risk dementia adults (DigiTAU Project).ResultsAlthough HCP consider asking patients and carers about technology use to be theoretically important (90.2%) and useful in practice (94.2%), they often do not do it (45.1%). There is incongruity when they feel safe to offer interventions by digital means (58.8%) but commonly agree, on average, that HCP are not prepared to use digiTech (51.0%). Despite having positive views towards benefits in adopting digiTech for patients (98.1%), they think they bring more benefits to families and caregivers than to patients themselves (56.9%). HCP consider digiTech will change their practice in the short term within 1 year (58.8%) and within 5 years (88.3%). None of the 8 options suggested as the most “promising” technology in 10 years reaches more than 25% of the choices.ConclusionsHCP have conflicting views about the usage of technologies by their patients and caregivers but expect some positive changes in their work practice. It suggests new digiTech must be submitted to scrutiny so that its applicability overcomes the challenges. Further studies and analysis are needed to understand better this data.
The Lonafarnib target, Rhes, is uniquely dysregulated in tauopathies: A human postmortem study
Authors: Ehrenberg Alexander J. , Leng Kun , Letourneau Kaitlin , Hernandez Israel , Lew Caroline , Seeley William W. , Spina Salvatore , Miller Bruce L. , Heinsen Helmut , Kampmann Martin , Kosik Kenneth S. , Grinberg Lea T. 
Published: December 2021

AbstractBackgroundThe farnesyltransferase inhibitor, Lonafarnib, is capable of reducing tau lesions and associated atrophy in tauopathy models through activity on the Ras GTPase, Rhes (Hernandez I et al., 2019). While hinting at a role of Rhes in tau proteinopathic etiology, it is unclear how Rhes activity changes in human tauopathies or other neurodegenerative diseases. As these models reflect rare, familial forms of tauopathy, we sought to detect evidence of Rhes changes in human sporadic tauopathy versus FTLD‐TDP and synucleinopathies.MethodAllocortical and neocortical sections from postmortem cases (Table 1) representing five different tauopathies, FTLD‐TDP, Lewy body disease, and healthy controls (HC) were immunohistochemically stained for Rhes, proteinopathic lesions (i.e. PHF‐1 positive tau inclusions, phospho‐TDP‐43, or α‐synuclein), and NeuN. Single‐nucleus RNA‐sequencing (snRNA‐seq) was also performed in a separate cohort representing HC and early AD.Result40 cases were examined in this study (Table 1). Rhes is widespread in cortical neurons, as detected by immunohistochemical staining and snRNA‐seq (Figure 1). In tauopathies, neurons either present Rhes as diffuse or punctiform, or feature an absence of Rhes (Figure 2). Accordingly, we classified neurons as Rhes type Diffuse, Punctiform, or Absent. The proportion of neurons with PHF‐1 positive tau inclusions significantly differ between the three neuronal Rhes phenotypes (p < 0.0001) with the majority of Absent type neurons harboring PHF‐1 positive tau inclusions and Diffuse type neurons mostly devoid of PHF‐1 positive tau inclusions (Figure 3, Table 2). Punctiform and Absent type neurons were not detected in neurons with phospho‐TDP‐43 inclusions or α‐synuclein inclusions (Figure 4).ConclusionGiven the distribution of PHF‐1 positive tau inclusions across different Rhes‐deliniated neuronal phenotypes, we propose a model by which Rhes takes on a punctiform phenotype then is ultimately cleared from neurons with tau lesions. This postmortem study in humans, together with in vivo and in vitro work done in familial tauopathy models, suggests the presence of a causal relationship between Rhes clearance and tau proteinopathic lesions, but not phospho‐TDP‐43 or α‐synuclein inclusions. As such, Rhes cellular phenotype represents a novel postmortem hallmark of tauopathy and supports to application of Lonafarnib to the treatment of tauopathies.
Effect of genetic and vascular AD risk factors on rate of cognitive decline in EOAD vs LOAD
Authors: Sanjay Apoorva Bharthur , Li Yunyi , Gao Sujuan , Apostolova Liana G. 
Published: December 2021

AbstractBackground
APOE ε4 and vascular factors are well‐known risk factors for developing AD. The effect of these risk factors on rate of cognitive decline in early‐ or late‐onset AD (EOAD and LOAD) is not well understood. We investigated the effect of known AD risk factors (APOE ε4, education, hypertension, diabetes, dyslipidemia, and obesity) on longitudinal cognitive decline in EOAD and LOAD.MethodCognitive and demographic data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study was used. We identified 203 EOAD and 1055 LOAD subjects based on age of onset of cognitive decline < or ≥65. Language function was assessed using the Boston Naming Test. Visuospatial function was assessed using ADAS‐Cog constructional praxis. Verbal memory was assessed by summing the scores of word recall (ADAS‐WRT),Delayed Word recall and Word recognition (ADAS‐Word). Executive function was assessed by using the category fluency test. For general cognition we used Mini‐Mental Status Examination (MMSE) and clinical dementia rating sum of boxes (CDR‐SB). To evaluate whether the risk factors had differential effect on the rate of cognitive decline between EOAD and LOAD, we performed univariable analysis for three‐way interaction (risk factor*time*group) and in multivariable analyses, we included age, time, risk factor, group, two‐way interaction effect (risk factor*group, time*group), and three‐way interaction effect (risk factor*time*group) that showed significance in univariable analyses for three‐ways interaction (p<.05).ResultBaseline characteristics and demographic of participants are described in (Table 1).
APOE ε4 carrier status was associated with significantly faster decline in language, visuospatial, verbal memory, executive function and MMSE in LOAD (p<0.05). In EOAD it was only associated with faster decline in language domain (p=0.046). LOAD carriers had slower rate of decline in CDR‐SB. Being overweight was associated with a significantly different rate of decline between EOAD and LOAD for visuospatial function (p=0.04) and MMSE(p=0.02). It was also significantly associated with faster decline in CDR‐SB(p=0.03) in EOAD. Obesity was significantly associated with faster decline in CDR‐SB in EOAD (p=0.004) but not LOAD (Table 2).ConclusionKnown risk factors for AD can have differential effect on type of cognitive trajectories based on age of onset of disease.
IPA criteria for psychosis in major and mild neurocognitive disorders
Authors: Reich Edgardo Gabriel 
Published: December 2021

AbstractBackgroundPsychosis is common among individuals with neurocognitive disorders, is difficult to manage, and causes considerable burden and stress to patients and caregivers. Developing effective treatments is a substantial unmet medical need but research has been slowed by the need for updated consensus diagnostic criteria. To address this need, the International Psychogeriatrics Association (IPA) initiated a process to develop criteria for clinical use, research, and treatment development efforts. This opening can be bolstered by some epidemiology – 5.8M AD, 20% with psychosis at some time in the illness.MethodThe process included clinical, regulatory, and industry stakeholders as well as input from a global network of experts in geriatric psychiatry responding to two surveys (N=336).Details on each survey and the meetingResultsThe consensus process confirmed that clinicians wanted elaboration of aspects of the definition proposed by Jeste and Finkel in 2000 to ensure that the criteria are applied appropriately. Based on discussions, the survey, and emerging research, criteria were revised to be applied to psychosis occurring with all major and mild neurocognitive disorders. Other important changes include providing examples of hallucinations and delusions and clarifying time course, impact, and exclusionary criteria.ConclusionsThis definition of psychosis in major and mild neurocognitive disorders can be used to advance many types of research including development of much needed pharmacologic and nonpharmacologic interventions for psychosis in patients with neurocognitive disorders.
Application of the IPA definition of agitation in cognitive disorders in clinical trials
Authors: Zhong Kate 
Published: December 2021

AbstractBackgroundIn 2015, the IPA published provisional criteria for Agitation in Cognitive Disorders. The criteria have since been extensively applied in clinical research and clinical trials. We review the impact of these criteria and the implications of their common use.MethodThe IPA criteria for Agitation in Cognitive Disorders were developed through an extensive process involving multiple stakeholders with two membership surveys, an in‐person meeting of international experts, and an iterative process of criteria and manuscript development. We reviewed the application of the IPA criteria in clinical trials since 2015 through interrogation of the clinicaltrials.gov registry.ResultsThere have been 21 clinical trials for agitation in Alzheimer’s diseases conducted since 2015, out of those, IPA criteria have been used as inclusion criteria in 11 trials, the other 10 trials did not identify the IPA criteria as the explicit entry criteria. There is trend for trials planned more recently to use the criteria (6 of 9 trials registered since 2018). The criteria have been used in clinical trials with agents of a variety of mechanisms of action: 7 different mechanisms are represented in the trials using the criteria.ConclusionsThe 2015 IPA provisional criteria for Agitation in Cognitive Disorder are widely used. They have been implemented as inclusion criteria in a majority of agitation trials conducted since their introduction. A variety of pharmacologic mechanisms are represented in the trials using the criteria; the criteria facilitated comparing efficacy across multiple agents. The convergent and concurrent validity demonstrated for the criteria support removal of “provisional” from the criteria.
CSF amyloid‐beta, tau, and neurodegenerative and inflammatory biomarkers in cognitively unimpaired late middle‐aged and older adult APOE ε4 homozygotes, heterozygotes, and non‐carriers from the Arizona APOE Cohort
Authors: Ghisays Valentina , Jansen Willemijn J. , Chen Yinghua , Protas Hillary D. , Malek‐Ahmadi Michael H. , Luo Ji , Lee Wendy , Chen Kewei , Su Yi , Caselli Richard J. , Zetterberg Henrik , Blennow Kaj , Reiman Eric M. 
Published: December 2021

AbstractBackgroundAPOE4 gene dose, the number of apolipoprotein E ‐ɛ4 (APOE4) ɛ4 alleles in a person’s genotype, is associated with higher Alzheimer’s disease (AD) risk and younger median age at dementia onset. We previously found relationships between PET, plasma, and CSF measurements of amyloid‐β (Aβ) pathophysiology in APOE4 gene dose. Here, we characterize the core AD CSF biomarkers (Aβ42/40, pTau181, tTau), the neurodegeneration marker neurofilament light chain (NfL) and the glial biomarkers soluble TREM2 (sTREM2), and glial fibrillary acidic protein (GFAP) measurements in age‐matched 48‐70 year‐old cognitively unimpaired (CU) APOE4 homozygotes (HMs), heterozygotes (HTs) and non‐carriers (NCs) from the Arizona cohort.MethodCSF biomarker measurements were performed at the University of Gothenburg using Lumipulse and ELISA immunoassays. CSF biomarker measurements were characterized and compared using linear‐tend ANOVAs in 12 HMs, 17 HTs, and 20 NCs who were CU, 48‐70 years old and did not differ significantly in their age, sex, or educational level.ResultAs expected, CSF Aβ42/40 ratios were inversely associated with APOE4 gene dose (linear trend, HM<HT<NC, p<0.05), and tTau/Aβ42 and pTau181/Aβ42 ratios were directly associated with APOE4 gene dose (HM>HT>NC p<0.05). Non‐significant trends suggested that CSF sTREM2 and sTREM2/pTau181 measurements were inversely associated with APOE4 gene dose (HM<HT≤NC, (0.05<p≤0.06). We failed to detect significant differences or linear trends in CSF pTau181, tTau, GFAP, or NfL measurements among these small subject groups.ConclusionAPOE4 gene dose is associated with measures of CSF Aβ42/40 and Aβ‐related tau pathophysiology, reflecting higher Aβ plaque burden in CU subjects close to their estimated ages at clinical onset. Additional studies are needed to clarify relationships between different Aβ, tau, neurodegenerative, inflammatory, and other CSF, or blood‐based biomarkers, and APOE4 gene dose in larger subject groups and at other ages.
Evaluation of a person‐centered electronic health record care plan for hospitalized patients with dementia
Authors: Smith Elisha J 
Published: December 2021

AbstractBackgroundHealth care for people with dementia (PWD) has been characterized as inconsistent in quality and fraught with potentially preventable encounters to hospitals (Petty et al., 2019; Phelan et al., 2012). Person‐centered care (PCC) is the preferred model of dementia care because it improves the quality of care and quality of life, yet acute hospital settings struggle to provide care that values personhood (Clissett et al., 2013).ObjectiveThis DNP scholarly project evaluated the effectiveness of the recently expanded, EHR‐embedded, Patient‐specific Dementia Information (PSDI) care plan and aimed to understand its interaction on nurse perception of dementia care, nurse knowledge of PSDI, and patient‐level outcomes guided by the Donabedian Model to measure its impact on enhancing dementia care delivery at a quaternary medical center.MethodNonexperimental, systematic program evaluation design. Pre‐ and post‐implementation survey measured the general attitudes of acute hospital nurses in providing care to persons with dementia, the extent to which they perceived their clinical practice as being person‐centered, and their general knowledge of the EHR tool. Weekly rounding assessed facilitators and barriers to individualizing patient care based on information extracted from the dementia care plan tool. EHR chart examined primary patient‐level outcome of dementia care quality in the acute care setting (length of stay, restraint use, constant observation, fall occurrence, and superimposed delirium).
ResultsThe findings illustrated reduction in fall occurrence, restraint use, and an increase in positive Confusion Assessment Method delirium screening. Though results from nurse survey demonstrated high level of perceived confidence in dementia care, thematic analysis revealed poor confidence in evaluating psychosocial needs. Thematic analysis and survey responses elucidated bedside coaching as in effective strategy to promote staff awareness and learning of the PSDI and PCC practices.ImplicationsIncorporation of PCC by hospital nurses through an EHR‐based care plan improves outcomes for hospitalized adults with dementia and reduce clinical complications. Further advancement can be made by utilizing the PSDI tool during care transition, offering robust education on dementia care, tailored bedside coaching techniques to teach concrete PCC intervention, promoting interdisciplinary involvement in PSDI workflow and future QI initiatives to improve care quality for PWD.