bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective factors associated with normal cognition in persons age 80 years and older
Authors: Trammell Antoine R , Hajjar Ihab , Goldstein Felicia C , Parker Monica W 
Published: December 2021

AbstractBackgroundIdentifying cognitive protective factors with aging is critical to addressing the development and progression of Alzheimer’s Disease and Related Dementias (ADRD). Despite evidence of cognitive resilience in African Americans (AA), older AA are at increased risk for ADRD. Studies exploring cognitive resilience have been conducted in predominantly white samples. Using a biracial sample, this study explores for factors related to normal cognition in persons over age 80.MethodData from the NACC through the November 2020 data freeze was requested. White and AA persons over age 80 with normal cognition (NC) and mild cognitive impairment (MCI) were analyzed. Demographics, functioning, medical and vascular factors, and medications were evaluated. Comparisons of white vs. AA and NC vs. MCI using ANOVA or chi‐square were performed. Multinomial logistic regression further evaluated race‐cognitive groups and potential factors related to normal cognition.ResultData from 20,088 subjects was reviewed. Mean age of the same was 85.7 years,15.3 years of education, and MoCA score of 23.7. It was 85.9% white, 57.8% female, and 36.2% had NC. AA/NC had higher BMI than AA/MCI (27.2vs.26.6,p=0.3). Most AA/NC were female (80.6%vs.74.4%,p<0.0001). AA/NC were non‐diabetic (61.4%vs.58.3%,p<0.0001) and lacked heart disease (7.4%vs.3.62%,p<0.0001). AA/NC lived independently (8.25%vs.3.01%,p<0.0001), were married (4.95%vs.1.97%, p<0.0001), and had intact problem‐solving (7.31%vs.1.95%,p<0.0001). Most white/NC were female (60.1%vs.47.3%,p<0.0001). White/NC were non‐diabetic (59.5%vs.31.3%,p<0.0001) and had no stroke (59.4% vs. 29.3%,p<0.0001). White/NC lived independently (55.3%vs.21.4%,p<0.0001), were married (28.9%vs.11.5%,p<0.0001), and had intact problem‐solving (55.7%vs.15.3%,p<0.0001). AA over age 80 were more likely to have NC if they lacked diabetes (OR:5.1,95%CI:1.38‐18.7), depression (OR:5.3,95%CI:1.33‐21.1), had intact problem solving (OR:4.26,95%CI:1.29‐14), and didn’t take ACEI (OR:3.59,95%CI1.58‐8.13) or diuretics (OR:3.51,95%CI1.71‐7.22). Whites over age 80 were more likely to have NC if they were female (OR:1.72, 9%CI:1.41‐2.11), had no depression (OR 2.93, 2.06‐1.14 95% CI), intact problem solving (OR:10.8,95%CI:6.43‐18.2), live with a spouse (OR:11.9,95%CI:1.46‐95.1), and not take antidepressants (OR:1.73,95%CI:1.35‐2.23).ConclusionDifferences in demographic and vascular factors, medications, and functioning are associated with normal cognition in advancing age. The factors can vary with race. Studies of prospective studies are needed to further study these differences.
Modified Mediterranean ketogenic diet resolves default mode network connectivity differences between adults with normal and impaired cognition
Authors: Kawas Mohammad I , Lockhart Samuel N. , Kim Jeongchul , Neth Bryan J. , Barcus Richard A. , Hughes Tim M. , Solingapuram Sai Kiran K , Craft Suzanne , Whitlow Christopher T. 
Published: December 2021

AbstractBackgroundIn the absence of disease modifying/preventative therapy for Alzheimer’s disease (AD), there has been increased focus on alternate therapeutic approaches, including the ketogenic diet, which supplies auxiliary metabolic fuel to brain and has potential neuroprotective effects. Our goal was to examine the modified Mediterranean‐ketogenic diet (MMKD) and an American Heart Association Diet (AHAD) in older adults at risk for AD with respect to cognitive performance and associated brain functional connectivity within the default mode network (DMN), which has been implicated in cognitive processes directed toward the self, such as introspection and autobiographic memory.MethodEighteen participants with normal cognition and subjective memory complaints (SMC) (n = 10, mean age = 65 ± 7) or Mild Cognitive Impairment (MCI) (n = 8, mean age = 64 ± 4) completed six weeks on both diets in a randomized crossover design. Before and after each diet, participants underwent 3T brain MRI and cognitive testing. MRI included T1‐weighted imaging for gray/white matter segmentation, and blood oxygen level dependent (BOLD) imaging for resting‐state functional connectivity. Cognitive function was evaluated using two memory tests, the Free and Cued Selective Reminding Test (FCSRT) and story recall, which were composited into a single memory score. BOLD data were pre‐processed and de‐noised using standard techniques, and normalized to the Mayo Clinic Adult Lifespan Template (MCALT). Connectivity analyses were performed using CONN functional connectivity toolbox. Briefly, functional connectivity of the DMN was analyzed utilizing the PCC for a seed to voxel connectivity analysis.ResultAt baseline, there were statistically significant differences in DMN connectivity between MCI and cognitively normal participants with SMC (Figure‐1), with connectivity increases between DMN and superior frontal gyrus, and decreases between DMN and superior parietal gyrus, which were significantly correlated with baseline memory scores (Figure‐2). After both diets, there were no detectable differences in DMN connectivity between the two groups. However, MMKD had a more pronounced effect on reducing DMN hyper‐connectivity among MCI participants than AHAD (Figure‐3).ConclusionOur results suggest that a ketogenic intervention may augment aberrant DMN network connectivity patterns in adults at risk for AD and lessen cognitive decline.
Using Bayesian hierarchical analysis to combine evidence across outcomes and trials
Authors: Dickson Samuel P , Nicodemus‐Johnson Jessie , Knowlton Newman , Syndergaard Tess , Neff Jacob , Earnshaw Madison , Hennessey Sean , Hendrix Suzanne B. 
Published: December 2021

AbstractBackgroundThe FDA’s statistical review for the recent aducanumab advisory committee included a Bayesian hierarchical analysis (BHA) combining CDR‐SB evidence across the ENGAGE and EMERGE studies resulting in a 62% probability of the treatment being efficacious. BHA can combine evidence across outcomes, trials within a drug development program, and trials for a specific mechanism of action, and provides an elegant solution to interpreting the totality of evidence. BHA is a comparable approach to composite scores and global statistical tests, but key differences exist.MethodUsing summary results from the aducanumab ENGAGE and EMERGE studies, solanezumab Expedition 1, 2, and 3 and the BAN2401 PRIME study, we combined evidence from ADAS‐Cog, ADCS‐ADL, and CDR‐SB using a BHA with hierarchies at the study, program, and three program level to assess the amyloid hypothesis, using the pre‐specified primary analysis populations. We compared these results to GSTs.ResultsThe aducanumab program combined across EMERGE and ENGAGE with all 3 outcomes has a 0.92 probability (>99.9% with GST), the solanezumab program combined across Expedition 1, Expedition 2 and Expedition 3 has a 0.92 probability (>99.9% with GST), and the BAN2401 program has a 0.95 probability (99.2% with GST) of treatment efficacy. We present BHA and GST results for individual studies compared to the original results. We also compare the study‐level BHA results to the global statistical test (GST) approach. We combine evidence across all 3 programs to get an overall probability of efficacy for the amyloid hypothesis with these 3 programs using BHA and GST.ConclusionBHA and GST both assess the totality of evidence within a study or development program, providing a natural correction for multiplicity, but results differ. BHA penalizes for divergence of outcomes or studies, and GST does not. This may be appropriate in some settings, but not in others. It allows an assessment of convergence of evidence, weakening of evidence, or elimination of evidence when a negative study “cancels out” a positive study. On a larger scale, it sheds light on how much evidence might exist for theories like the amyloid hypothesis when combining evidence across programs.
Potential anti‐Alzheimer alkaloids of Peganum harmala
Authors: Nasibova Tohfa , Garaev Eldar 
Published: December 2021

AbstractBackgroundAlzheimer's disease (AD) is an irreversible, progressive brain condition that steadily affects the ability to perform the simplest tasks, memory and reasoning skills, and ultimately. In 2018, the latest year for which data is available, it is officially reported 122,019 deaths from AD, which makes Alzheimer's the sixth leading cause of death and the fifth leading cause of death among people aged 65 and older in the United States. Deaths resulting from stroke, HIV, and heart disease decreased between 2000 and 2018, while recorded Alzheimer's deaths increased by 146,2 %.Different types of drugs are used against Alzheimer's disease. One of the medicines used for the treatment of Alzheimer's disease is acetylcholinesterase inhibitors (AChEIs). Methanol extracts of the seeds of the Peganum genus were found to show the significant inhibitory activity for acetylcholinesterase enzyme (AChE). Due to the beneficial effects of Peganum harmala alkaloids (harmine, harmaline, etc.) on the nervous system, the positive effects on Alzheimer's disease have been identified in studies. Our study aims to obtain these alkaloids from plants individually.MethodDried and ground grains of P. harmala are extracted 3 times by 95% ethanol. Extracts are combined, evaporated until a concentrated mass is formed, mixed with 5% HCl and the obtained solution is filtered. The solution is alkalized by 25% ammonia solution and extracted by liquid/liquid extraction with chloroform 4 times. Fractions are combined, concentrated, and analyzed by TLC. On TLC plates, 4 orange spots with Rf 0.69, 0.31, 0.2 and 0.1 (stationary phase “Sorbfil” (Russia), mobile phase chloroform/methanol, 9/1, v/v; revelator Dragendorff solution) are observed. For the purification, preparative TLC plates were used (stationary phase “Machery ‐ Nagel” (Germany), mobile phase chloroform/methanol, 8.5/1.5, v/v). Lines corresponding to each compound were scraped, extracted by ethanol, and filtered.ResultBased on UV, IR, and NMR spectroscopy data, these compounds were identified as harmaline, harmine, and vasicine.ConclusionThe wide distribution area, high quantity of alkaloids, and the positive effects of this plant on Alzheimer's disease make it possible to evaluate it as a potential medicine for the treatment and prevention of the disease.
Aβ42/Aβ40 ratio in plasma predicts amyloid‐PET status in amnestic‐MCI patients
Authors: Pascual‐Lucas María , Sarasa Leticia , Molina Elisabet P. , Castillo Sergio , Pesini Pedro , Allué Jose A. 
Published: December 2021

AbstractBackgroundWe have completed the analytical validation of an antibody‐free, HPLC‐MS/MS method (ABtest‐MS), to quantitate specifically Aβ1‐40 and Aβ1‐42 in plasma with high precision (inter‐assay %CV 6.2‐7.0% for Aβ1‐40 and 6.1%‐11.0% for Aβ1‐42) and accuracy (%RE ‐0.6 to 0.3% for Aβ1‐40 and ‐1.5 to 1.3% for Aβ1‐42).Previous studies have shown that the Aβ42/Aβ40 ratio in plasma predicts β‐amyloid status reliably, suggesting that the assessment of plasma Aβ levels could be a useful screening tool for Alzheimer’s Disease (AD) clinical trials, reducing the need for invasive or complex procedures.In this work we explore the ability of Aβ42/Aβ40 plasma ratio to predict the Aβ‐PET status at baseline visit in the ABvac40 (an active vaccine against Aβ40) phase II clinical trial.MethodAβ40 and Aβ42 plasma levels from 73 amnestic‐MCI (a‐MCI) participants, who had previously given their consent, were quantitated with ABtest‐MS. Levels of p‐tau181 were assessed with Simoa® p‐tau181 V2 Advantage Kit (Quanterix). The ability of plasma Aβ42/Aβ40 ratio or p‐tau181 to detect Aβ‐PET positivity was assessed as the area under the ROC curve (AUC).ResultAβ42/Aβ40 plasma ratio values were significantly lower in the Aβ‐PET positive than in the Aβ‐PET negative group (p<0.001). The opposite trend was observed for p‐tau181 plasma levels, which were significantly higher in the Aβ‐PET positive than in the Aβ‐PET negative group (p<0.001). The Aβ42/Aβ40 plasma ratio discriminated Aβ‐PET positivity with an AUC value of 0.87, performing identically to p‐tau181 plasma levels.A negligible increment in the AUC was observed after adjusting for ApoE genotype. However, inclusion of both biomarkers in the predictive model increased AUC value up to 0.94, outperforming each biomarker alone.ConclusionAmong the a‐MCI participants in the ABvac40 phase II clinical trial who had previously consent, the Aβ42/Aβ40 plasma ratio discriminates Aβ‐PET positivity with a high AUC, performing as well as p‐tau181. These results demonstrate that the Aβ42/Aβ40 ratio in plasma could be used to predict cerebral Aβ burden.
Utility of extracellular vesicles and their MicroRNA cargo as biomarkers for Alzheimer's disease
Authors: Sandau Ursula S. , McFarland Trevor , Smith Sierra J. , Baker Sarah Catherine , Duggan Erika , Nolan John P. , Saugstad Julie A 
Published: December 2021

AbstractBackgroundAlzheimer’s disease (AD) is the most common cause of dementia. Developing effective therapies is dependent on the availability of biomarkers that accurately diagnosis AD and track disease progression. MiRNAs, which can be sorted into extracellular vesicles (EVs), reflect the disease state of many neurological disorders and have the potential to serve as biomarkers.MethodCerebrospinal fluid (CSF) from AD, Parkinson’s disease (PD), and control (n=10/group) participants was analyzed by vesicle flow cytometry for size, concentration, and subtypes of EVs. In matching CSF and isolated CSF‐EVs we measured the expression of 34 miRNAs (previously validated candidate AD biomarkers) and assessed magnitude of fold change and classification potential for AD.ResultThe EVs in CSF from AD and PD were significantly larger than control CSF and there were fewer microvesicles. CSF‐EVs had 25 detectable miRNAs out of 34 assayed; while 30 were detectable in total CSF. For the detectable miRNAs in CSF‐EVs, 52% had at least a 1.5 fold change in expression in AD, relative to control. In total CSF, 30% of the assayed miRNAs had a 1.5 fold change in AD versus control. Classification performance for AD from controls was improved for CSF‐EV miRNAs, compared to total CSF. Four of the CSF‐EV miRNAs also had an AUC > 0.7 for classifying AD from PD.ConclusionEV biogenesis in neurodegenerative diseases is disrupted compared to neurologically normal controls, which leads to an altered EV profile in CSF. Further, the miRNA expression profile of CSF‐EVs improves the performance of candidate AD biomarkers.
A study on the research trends of effectiveness of telehealth for the elderly through bibliographic analysis
Authors: Park SunHa 
Published: December 2021

AbstractBackgroundTelemedicine is being proposed as an alternative to the problem of medical restrictions on elderly in an aging society. However in Korea, telemedicine for the elderly is not in full swing and the need for telemedicine is increasing. In order to obtain implications for the study of the effectiveness of telemedicine for the elderly in Korea, it was intended to analyze overseas research trends empirically through the bibliographic analysis.MethodThis study collected bibliographic information on the effectiveness of telehealth for the elderly published in international academia from January 2010 to December 2020 and analyzed and visualized relationships between information using VOS viewer software.ResultFirst of all, research trend analysis shows 678% increase or decrease in the number of papers published over the past 10 years. The research field was the most conducted in 145(45.89%) health care science services, and the most papers were published in 39 Telemedicine and e‐Health journals(9.11%). Second, the network analysis showed that the total connectivity of Oxford University among countries and institutions in the U.S. was 65, respectively, indicating the strongest influence in international academic societies. Third, as a result of keyword analysis elderly(64 times), treatment(62 times), health(50 times), technology(40 times), and results (41 times) were used in the paper.ConclusionIn this study, trends and topics of international academia on the effectiveness of telehealth for the elderly will be analyzed to gain implications for the research activation and institutional basis of telehealth for elderly in Korea.
Why would Canada have the longest wait times for an Alzheimer’s treatment among the G7 countries? A policy analysis
Authors: Mattke Soeren , Wang Mo 
Published: December 2021

AbstractBackgroundThe emerging disease‐modifying Alzheimer’s treatments present a health system challenge because of the combination of a large prevalent patient pool and a complex diagnostic process. Analyses of system preparedness have projected Canada to have by far the longest and most protracted wait times for access among G7 countries.MethodPolicy analysis study using comparative health system data and 17 semi‐structured interviews with experts in Canada.ResultCompared to other G7 countries, Canada has a high number of family physicians, but low numbers of dementia specialists and imaging equipment per capita, leading to wait times even today. The capacity constraints result from limited investment in infrastructure and deliberate use of supply side restrictions for cost containment. Several options exist to alleviate those constraints in the short run, such as building on existing primary‐led memory care models, more flexible use of existing imaging devices, and utilization of novel diagnostic technology like digital and blood‐based biomarker tests.ConclusionCanada faces a unique challenge to make a disease‐modifying Alzheimer’s treatment accessible because of limited capacity for memory care. While opportunities exist to improve access, they are not likely to be realized fast enough in the absence of a deliberate planning effort.
Identifying preclinical Alzheimer disease from driving patterns: A machine learning approach
Authors: Bayat Sayeh , Babulal Ganesh M , Schindler Suzanne E. , Fagan Anne M , Morris John C. , Mihailidis Alex , Roe Catherine M 
Published: December 2021

AbstractBackgroundAlzheimer disease (AD) is the most prevalent form of age‐related dementia. The clinical manifestation of AD is generally preceded by a silent preclinical phase during which early AD brain changes are present but dementia symptoms have not yet appeared. Molecular biomarkers have been used to ascertain the presence of AD brain changes, which are obtained via imaging and lumbar puncture. However, the widespread use of these methods is limited by cost and availability. Therefore, there is a need for a non‐invasive and low‐cost solution for identifying individuals who are likely to have preclinical AD. Since the preclinical phase of AD has been shown to impact driving, daily driving behaviours captured using Global Positioning System (GPS) devices can serve as a digital biomarker to detect preclinical AD. The objective of the present study is to use machine learning methods to evaluate the ability of in‐vehicle GPS devices to distinguish cognitively normal older drivers with preclinical AD from those without preclinical AD.MethodWe used commercial in‐vehicle GPS devices to study the naturalistic driving behaviours of 144 cognitively normal older drivers (aged 65+) over one year. The cohort included 69 individuals with and 75 without preclinical AD, as determined by cerebrospinal fluid (CSF) biomarkers. Four Random Forest (RF) models were trained with three sets of variables: (1) driving features only, (2) driving features and age, and (3) driving features, age and APOE ε4 status. Finally, the strongest predictors of preclinical AD were identified using an RF‐based Recursive Feature Elimination technique.ResultThe F1 score of the RF models for identifying preclinical AD was 82% using GPS‐based driving indicators, 88% using age and driving indicators, and 91% using age, APOE ε4 status and driving. The area under the receiver operating curve for the final model was 0.96. APOE ε4 status and age were the two most important features for predicting preclinical AD, and the most important driving feature was the vehicle’s jerk, which is a measure of driving smoothness.ConclusionDriving behaviours captured with GPS can accurately distinguish cognitively normal older drivers with preclinical AD from those without preclinical AD.
Perceptions of and needs for e‐Health solutions for elderly people with cognitive impairment, their caregivers and health care providers: A qualitative exploration
Authors: Gagnon Marie‐Pierre , Boucher Mylene , Ndiaye Mame‐Awa , Dequanter Samantha , Buyl Ronald , Gorus Ellen , Fobelets Maaike , Sasseville Maxime , Barony Romina 
Published: December 2021

AbstractBackgroundThe prevalence of mild cognitive impairment (MCI) and mild neurocognitive disorder (mNCD) are steadily increasing in Canada. Information and communication technologies (ICTs) in health represent an innovation to promote home care and autonomy for people with various degrees of cognitive impairment. The objective of this study is to develop a web‐based multicriteria decision support tool adapted to older adults with MCI or mNCD, their informal caregivers, and health care providers (HCPs) to support the development and implementation of ICTs adapted to the needs and preferences of people with cognitive impairments and their caregivers.MethodsWe used a participatory research strategy to develop of a decision support tool for the use of ICTs focused on the needs of patients, their caregivers, and HCPs. Data collection consisted of semi‐structured interviews with elderly people with MCI (N = 10) and caregivers of people with mNCD (N= 7) to explore their current knowledge and perceptions of various ICTs as well as their needs and preferences for such interventions and a focus group with HCPs to understand their perceptions of the needs of seniors with MCI and caregivers of people with mNCD.ResultsICTs are seen as a beneficial solution to promote home care and autonomy for people with cognitive disorders. ICTs provide a sense of security and peace of mind, especially for caregivers of people with mNCD. However, the complexity and high cost of ICTs as well as the lack of support appear to be major limits to their use. HCP recognize the value of e‐Health but claim to lack reliable information and were therefore highly unsure to recommend its use.ConclusionsPeople suffering from cognitive disorders and their caregivers are generally open to technological developments and favour the use of ICTs. For health professionals, continuous training on ICTs would make them more comfortable to recommend them to patients and their families. Although the use of ICTs is promising for maintaining elderly people with cognitive disorders at home, our study shows that it will be necessary to find ways to make them accessible to promote their use.