bluuebunny/crossref_metadata_2025_split huggingface dataset:
Institutional experience on cognitive screening at the Medicare Annual Wellness Visit
Authors: Lee Patricia R , Godfrey Wesley B , Raza Arwa , Xi Romi , Brea Carolina , Smith Zhana , Schnell Patrick M , Li Guibin 
Published: December 2021

AbstractBackgroundScreening for cognitive impairment is required at Medicare Annual Wellness Visits (AWV). Subjective or objective methods are suggested, but there is no one screening tool specified by Centers for Medicare and Medicaid Services (CMS). We assessed screening methods, its outcomes, and potential disparities in cognitive screening at AWV.MethodRetrospective chart reviews were done for 1,493 adults 55+ who had initial AWV at a single academic medical center ambulatory site between January 2011 and March 2017. Demographics, assessment type, and positive screens noted by provider were collected. Subjective assessments were by history/direct observation alone. Objective assessments are noted in Table 1. Multiple logistic regression with stepwise variable selection via AIC were done.ResultsMean age was 73.6 years (SD=7.9); 828 (55.5%) were female; 1191 (79.8%) were white (Table 2). 1,311 were screened for cognitive impairment, 120 were not screened, and 62 had an established diagnosis. Of those screened, 87.5% were screened using objective methods; greater age (p<0.001), African American race as compared to white race (p<0.001), and non‐English primary language (p=0.03) were associated with increased probability of positive screens. In subjective screening (n=163), speaking a non‐English primary language was associated with higher probability of positive screening (p = 0.04). In patients with positive screens through any method, 41 had no further cognitive assessment planned, 19 had plans for follow‐up, 15 were referred to neurology.ConclusionAWV are an opportunity to screen for underdiagnosed cognitive impairment. Clinicians in our study used a myriad of tests, despite each test’s unique limitations. Greater age, African American race, non‐English primary language being associated with increased probability of positive objective screening is consistent with the literature. In subjective screenings, patients with non‐English primary language were more likely to screen positive, suggesting that in AWV, non‐English speaking patients may be at a disadvantage for standard cognitive screening. Despite positive cognitive screening, the majority had no further cognitive assessment planned during the visit. Our study suggests that more research should focus on a standardized cognitive screening and decision making after a positive cognitive screening at AWV.
Associations between apathy and fatigue in patients with neurocognitive disorders
Authors: Daumas Lyne , Manera Valeria , Robert Philippe , Zory Raphael 
Published: December 2021

AbstractBackgroundApathy and fatigue are two disabling symptoms of neurocognitive disorders causing a reduction of activity in daily functioning, including in motor activity, and contributing to loss of autonomy. Fatigability is characterized by a reduction in the ability to produce a motor work during a physical task and is a central element in the circle of deconditioning because many activities of daily living require the ability to exert effort over an extended period of time. This study aims to explore the fatigability of apathetic and non‐apathetic patients with neurocognitive disorders (ND).Method20 subjects (out of 40 still to include) with mild to major ND (age= 78,0 ± 6,3y, MMSE= 26,0±2,3) were classified as apathetic (n=10, BMI= 25 ± 2,5) vs non‐apathetic (n=10, BMI= 25 ± 4,5) based on the apathy diagnostic criteria[1]. Subjects performed a 6 minutes walk test, a handgrip test with a sustained maximal isometric contraction for 15 seconds, and a sit to stand task until exhaustion surrounded by a maximal voluntary contraction of extensors knee.ResultPreliminary results showed a significant greater decrease of performance in apathetic patients during the handgrip sustained maximal isometric test (p=0,028). On the 6 minutes walk test and the sit to stand task, no significant differences of fatigability index were found between two groups.ConclusionThe greater decrease of performance during the handgrip test suggests a higher fatigability in apathetic ND patients. This is not yet confirmed by the two other tasks, probably due to the small sample size. As data collection for the study will finish in June 2021, I will present at the conference more reliable results. Reference: [1] Robert P, Lanctôt KL, Agüera‐Ortiz L, et al. Is it time to revise the diagnostic criteria for apathy in brain disorders? The 2018 international consensus group. Eur Psychiatry. 2018;54:71‐76.
Associations between the use of histamine‐2 receptor antagonists vs. proton pump inhibitors and cognitive decline: A stratified longitudinal study in people with and without cognitive impairment
Authors: Wu Che‐Yuan , Xiong Lisa Y , Ouk Michael , Edwards Jodi D , Rabin Jennifer S , Herrmann Nathan , Lanctôt Krista L , Kapral Moira K , Law Marcus , Swardfager Walter 
Published: December 2021

AbstractBackgroundStudies suggest associations between proton pump inhibitors (PPI) and higher dementia risk compared with no use; however, several studies did not consider histamine‐2 receptor antagonists (H2RAs), the other common acid suppressant for similar indications. Comparisons between them are clinically relevant, both in older people with and without cognitive impairment due to Alzheimer’s disease (AD).MethodParticipants using a PPI or H2RA were selected from the National Alzheimer's Coordinating Center database from September 2005 to February 2021. Cox regressions were used to compare 5‐year conversion from normal cognition to mild cognitive impairment (MCI) or dementia, and 5‐year conversion from MCI to dementia, between PPI and H2RA users. In a propensity score matched sample of clinically diagnosed mild‐moderate AD, a linear mixed‐effects regression was used to assess PPI vs. H2RA use in rates of decline in global cognition (Clinical Dementia Rating [CDR®] Sum of Boxes; CDR‐SOB) up to 5 years. Delayed memory recall (Wechsler Memory Scale–Logical Memory test) was explored using a mixed‐effects negative binomial regression. Demographics, smoking, alcohol abuse, baseline CDR‐SOB, comorbidities, concurrent medications used, and apolipoprotein E genotype were included as covariates in Cox regressions or in propensity score.ResultCognitively normal H2RA (n=547, events=62) vs. PPI users (n=2237, events=312) did not differ in their risk for MCI or AD (Hazard Ratio; HR [95% Confidence Interval; CI] = 1.067 [0.807‐1.410]). In MCI, H2RA use (n=288, events=75) was associated with faster 5‐year dementia conversion (HR [95% CI] = 1.402 [1.085‐1.811]), compared with PPI use (n=1413, events=355). In AD, H2RA (n=212) vs. PPI (n=636) use was not associated with differential rates of decline in global cognition (B [95% CI] = ‐0.023 [‐0.324, 0.277] CDR‐SOB per year). However, H2RA use was associated with faster memory decline (Rate Ratio [95% CI] = 0.783 [0.671‐0.915]) in AD, but no associations with memory decline were found in MCI or normal cognition.ConclusionDifferential associations with cognitive decline were not observed in cognitively normal older people. Among people with MCI or AD, H2RA use was associated with faster rates of conversion to dementia, or memory decline, respectively. Anti‐cholinergic burden might explain the associations.
ICARE AD‐US: Design of a prospective, single‐arm, multicenter, noninterventional real‐world study of aducanumab in the United States
Authors: Galvin James E. , Cummings Jeffrey L. , Benea Mihaela Levitchi , de Moor Carl , Atri Alireza , Porter Verna R. , McEwen Sarah C. , Rubino Ivana 
Published: December 2021

AbstractBackgroundAducanumab is a human monoclonal antibody that selectively targets aggregated forms of amyloid beta (Aβ), including soluble oligomers and insoluble fibrils, and, at the writing of this abstract, is currently under review by the US Food and Drug Administration (FDA), European Medicines Agency, and Pharmaceuticals and Medical Devices Agency (Japan). The efficacy and safety of aducanumab have been evaluated in 2 identically designed, randomized, placebo‐controlled, double‐blind Phase 3 studies in early Alzheimer’s disease (AD); however, should aducanumab be approved, it will be critical to effectively evaluate its long‐term impact in the real world.MethodICARE AD‐US is a prospective, single‐arm, multicenter, noninterventional study of aducanumab, as prescribed in a postmarketing, real‐world US setting. This Phase 4 observational study is designed to evaluate the safety and effectiveness of aducanumab in real‐world clinical practice per its FDA‐approved labeling in the US. The primary objective of the ICARE AD‐US study is to evaluate progression of AD in aducanumab‐treated patients as determined by a predefined, uniform set of cognitive, functional, and neuropsychiatric and global severity measures and to characterize the longitudinal impact of aducanumab on quality of life, disease burden, and health care resource utilization. ICARE AD‐US will also assess the long‐term safety of aducanumab as measured by the incidence of serious adverse events and the incidence of amyloid‐related imaging abnormalities‐edema (ARIA‐E). Biobanking of collected blood (plasma and serum) will provide the opportunity for future biomarker studies.ResultICARE AD‐US aims to enroll approximately 6000 patients with AD over 4 years, including approximately 500 African American and 500 Hispanic/Latinx patients, from approximately 200 sites in the US. Patients will be monitored in a real‐world setting for a period of up to 5 years.ConclusionThe evidence generated in the ICARE AD‐US study will not only enable the collection of consistent long‐term efficacy and safety data to assess the impact of aducanumab treatment in the real world but will also support the measurement and characterization of AD progression and the optimization of clinical practice through standardization of the diagnosis of early AD and identification of individuals who may benefit from treatment.
Leukotriene receptor antagonist use is associated with slower cognitive decline in Alzheimer’s disease
Authors: Xiong Lisa Y. , Ouk Michael , Wu Che‐Yuan , Rabin Jennifer S. , Lanctôt Krista L. , Herrmann Nathan , Black Sandra E. , Edwards Jodi D. , Swardfager Walter 
Published: December 2021

AbstractBackgroundRepurposing of leukotriene receptor antagonists (LTRAs), originally developed for asthma, is currently being explored in the treatment Alzheimer’s disease (AD). Animal studies have shown that administration of the LTRA montelukast has neuroprotective effects and can improve memory and cognition in rodents; however, there is limited evidence supporting the neuroprotective effects of LTRAs in humans.MethodsParticipants with AD dementia were identified in the National Alzheimer's Coordinating Center database. LTRA (montelukast or zafirlukast) users were propensity matched 1:3 to non‐users on age, sex, education, body mass index, smoking history, concomitant use of medications for dementia and other respiratory medications (for allergy, chronic obstructive pulmonary disease, and asthma), APOE ε4 carrier status, CDR® Dementia Staging Instrument global score, and vascular brain disease. Cognitive domains including immediate and delayed memory (Weschler Memory Scale Revised – Logical Memory IA and IIA), psychomotor processing speed (Digit Symbol), and language (Animals, Vegetables, and Boston Naming Test) were compared between users and non‐users in mixed‐effects linear or Poisson regression models, as appropriate for the data distribution, yielding unstandardized regression coefficients (B) and rate ratios (RR), respectively.ResultsAmong n=604 people with AD dementia (mean age 75.3±10.0 years, 59.3% female, mean education 14.0±4.0 years, 55.1% APOE ε4 carriers, mean follow‐up 2.5±2.6 years), LTRA use was associated with a slower decline in psychomotor processing speed, as measured by the Digit Symbol test (Β=1.466 [0.253,2.687] symbols/year), and a slower decline in language, as measured by Animals (Β=0.541 [0.215,0.866]animals/year), Vegetables (B=0.309 [0.056,0.561] vegetables/year), and the Boston Naming Test (B=0.529 [0.005,1.053] words/year). Effect sizes were relatively small (range 0.069‐0.101) and persisted after controlling for a 10% false discovery rate. LTRA use was not associated with a change in performance for immediate (RR=1.047 [0.970,1.129]) or delayed memory (RR=1.062 [0.929,1.215]).ConclusionThese results indicate that use of an LTRA may have benefits for preserving function for select cognitive domains in individuals with AD dementia. The leukotriene pathway may represent a target for the treatment of AD dementia and the role of leukotrienes and their receptors in cognitive decline warrants further investigation.
A machine learning approach to predict reversion from mild cognitive impairment to normal cognition: A population‐based cohort study
Authors: Sha Feng , Bi Jiefeng , Wei Chang , Zhao Ziyi , Li Bingyu 
Published: December 2021

AbstractBackgroundPredicting the probability of the reversion from mild cognitive impairment (MCI) to cognitively normal (CN) status can inform preventive treatments at individual, institutional and social level. This study aims to build a prediction model using a machine learning approach for reversion from MCI to CN status.MethodThe study included 7,422 participants above 65 years old with MCI from Chinese Longitudinal Health Longevity Survey (Figure 1). LightGBM was used to build a prediction model of 154 variables, including individual and household socioeconomic status, dietary/lifestyle, cardiometabolic, psychological factors and history of diseases. SHAP values were used to interpret the impact of the top 40 variables that contributed to the LightGBM model. Multivariable Cox regression with elastic net penalty was also conducted for comparison. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC).Results1,604 (21.6%) participants reversed from MCI to CN with a median follow‐up of 2.8 years. The top 40 features were presented in the figure 2. The concordance index of the LightGBM model was 0.71, which is much higher than the traditional multivariable Cox regression with elastic net penalty (0.66).ConclusionThe machine learning approach could develop a more accurate early identification of recovery of MCI patients. The predicting can guide the recovery process of MCI patients.
Comprehensive geriatric assessments for long‐term and home care settings and digital platforms available to support their applicability: A systematic review
Authors: Ulate Mauricio Molinari , Asl Aysan Mahmoudi , Vidales Esther Parra , Sánchez Juan Luis Muñoz , Martin Manuel Angel Franco , van der Roest Henriëtte G. 
Published: December 2021

AbstractBackgroundIntegrated care delivery is regarded as the most effective way of care provisioning to tackle challenges of dementia care, such as uncoordinated care, risk of hospitalizations, care planning and unmet needs. As Comprehensive Geriatric Assessments (CGAs) incorporate the key principles of integrated care, implementing CGAs in care practice might be highly relevant. However, this implementation should be supported by Digital Health Interventions in order to reach the full CGA capacity.Aims: To present the state‐of‐the‐art evidence on available CGAs for long‐term and home care, and digital platforms supporting the administration of CGAs.MethodsTwo search strategies were conducted in PubMed, CINAHL, and Web of Science. One focused on the validity and reliability of available CGAs for long‐term and home care settings, and the second search comprised digital platforms that support CGAs. Studies in English and Spanish and published up to July 30, 2020 were considered.ResultsA total of 73 studies reporting on the validity/reliability of 14 different CGAs, and five papers describing four digital platforms supporting CGAs were identified. Most of the CGAs covered a wide range of domains, evidence for good to excellent validity and reliability was reported for various instruments. Digital platforms showed some limitations and barriers regarding their usability and feasibility.ConclusionForemost, strong evidence of good to excellent validity and reliability was found for the Resident Assessment Instrument‐Minimum Data Set (RAI‐MDS) and subsequent updated instruments, similar results have been reported for multiple countries. For this reason, we recommend the use of its latest versions for long‐term care facilities and home care, the interRAI LTCF and interRAI HC. Regarding the digital platforms supporting CGAs, the inclusion of safe data storage, automatic notifications for assessment completion, individualized profile reports, automatic calculation of final outcomes, and facilitation of multidisciplinary assessments, were identified as key features to enhance their implementation. This project is part of the Marie Skłodowska Curie Actions Innovative Training Network H2020‐MSCA‐ITN, under grant agreement number 813196.
Recommendations of the International Working Group for the clinical diagnosis of Alzheimer’s disease
Authors: Dubois Bruno , Villain Nicolas , Frisoni Giovanni , Rabinovici Gil D. , Sabbagh Marwan Noel , Cappa Stefano , Bejanin Alexandre , Bombois Stéphanie , Epelbaum Stéphane , Teichmann Marc , Habert Marie‐Odile , Nordberg Agneta K. , Blennow Kaj , Galasko Doug R. , Stern Yaakov , Rowe Christopher C. , Salloway Stephen P. , Schneider Lon S. , Cummings Jeffrey L. , Feldman Howard 
Published: December 2021

AbstractBackgroundIn 2018, the National Institute of Aging and the Alzheimer Association proposed a purely biological definition of Alzheimer’s disease (AD) relying on biomarkers. While the intended use of the framework was for research purposes, it has engendered debate and challenges regarding its application in everyday clinical practice.MethodWe performed a literature review and pointed out the limitations of the current purely biological definition of AD.ResultNeuropathological studies have shown that amyloid β plaques and tau tangles are often accompanied by other pathologies, so ascribing the clinical phenotype to an amyloid or tau biomarker result might be difficult. In asymptomatic people, the detection of abnormal biomarkers is fraught with problems relating to uncertainty about the prognosis, and complex judgments and ethical issues about communicating results. Even defining biomarker categories is not simple, because methods for determining positivity are not always straightforward and nominally negative biomarker values can be associated with future cognitive decline. New clinical framework proposition: To address these concerns, the IWG advocates a return to Alzheimer’s disease as a clinical‐biological entity, characterised by amyloid β and tau biomarkers plus a typical clinical phenotype. We advise against measurement of amyloid β and tau biomarkers in asymptomatic people because of unreliable predictive power; nevertheless, we do provide a risk stratification scheme for such people, and abnormal amyloid β and tau biomarkers are thought to confer high risk. However, such individuals are categorised as being asymptomatic at risk of progression, not as having AD. In symptomatic people, we stress the importance of a careful clinical evaluation in view of the common occurrence of multiple pathologies, borderline biomarker measurements, and conflicting findings.ConclusionThese new recommandations of the IWG are the opportunity to debate about the definition of AD and the use of biomarkers in clinical practice and pharmacological trials. This developing topic should open a significant discussion between AD specialists (both physicians and scientists) at the 2021 AAIC.
Shining new light on dementia treatment: ADAS‐Cog and quantitative EEG evidence of cognitive improvement in early and mid‐stage dementia using self‐administered 1070 nm transcranial near‐infrared photobiomodulation
Authors: Berman Marvin H 
Published: December 2021

AbstractBackgroundThe current evidence supporting nonpharmacologic treatment of dementia has focused mainly on environmental or interactive interventions, e.g., music, sensory stimulation, simulated presence, and validation therapies. Exercise and light therapy improved/maintained activities of daily living, while cognitive stimulation, exercise and reminiscence improved cognition. The strongest evidence for reducing emotional disorders so far has employed music, psychological interventions and reminiscence. PubMed lists 918 citations related to non‐pharmacological treatments for dementia with music therapy and behavioral management techniques being the most efficacious showing modest improvements at best. Non‐pharmacologic treatment interventions directed at reversing both cognitive and behavioral symptom of dementia are small, few in number and with wide variation in defining outcome measures, and little comparative data across approaches to guide further research efforts or systematic clinical applicability. Photobiomodulation using brief, daily, pulsed LED‐driven transcranial infrared light stimulation, has been shown to markedly alter both cognitive and behavioral symptoms in people with mild to moderate dementia. Improved functioning has been documented by both standard neuropsychological testing and noninvasive Quantitative electroencephalographic (QEEG) measures of functional connectivity. This presentation describes a multi‐site, randomized, placebo controlled, at‐home, self‐administered treatment protocol employing pulsed transcranial and intraocular 1068nm near‐infrared light to achieve reversal of cognitive decline, and improve dementia patient’s physical and interpersonal behavior. Study subjects (n=100) were evaluated at two locations at baseline, midpoint (30 days) and termination (60 days) using both Quantitative EEG and ADAS‐Cog and caregiver evaluation of subject’s change in ADLs. This trial was a replication of an earlier pilot trial and a recent safety/feasibility trial with no adverse events reported in any study. MMSE improved 21.0%, 4.8 points in the active treatment group and 1.6 points in the placebo group. Sleep duration increased in the active treatment group by an hour after 8 days of treatment and caregivers noted improved mood, energy, and positive engagement in daily activities. None of these functional changes were noted in the placebo arm subjects. Active group’s clock drawing improved 20% and no change in the control group. Logical memory recall improved 3.3 points (p< .03) and time to completion of Trails A&B decreased 23.7% (p<.03).