bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interaction between amyloid and neuroinflammation on apathy along the Alzheimer’s disease spectrum
Authors: Stevenson Alyssa , Tissot Cécile , Kang Min Su , Benedet Andréa Lessa , Rahmouni Nesrine , Therriault Joseph , Pascoal Tharick A. , Chamoun Mira , Lussier Firoza Z. , Savard Mélissa , Mathotaarachchi Sulantha , Thomas Emilie , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2020

AbstractBackgroundThe Apathy Inventory is a rating scale given to informants in order to assess levels of apathy globally. This neuropsychiatric symptom is the most common noncognitive symptom in Alzheimer’s disease (AD), and it causes a great burden on diseased individuals and their caregivers. Even though it has been closely related to cerebrospinal fluid levels of neuroinflammation and amyloid, the interactive effect of pathologies is still unclear. Here we test the interaction between amyloid and neuroinflammation in the brain with apathy, along the AD spectrum.MethodWe assessed 59 individuals (38 cognitively unimpaired, 15 mild‐cognitive impairment, 6 AD) with [11C]PBR28‐neuroinflammation positron‐emission tomography (PET) and [18F]AZD4694‐amyloid PET. [11C]PBR28 and [18F]AZD4694 uptake value ratios (SUVRs) used the cerebellum grey matter as the reference region and were calculated 0‐90 min post‐injection and 40‐70 min post‐injection respectively. A voxel‐based regression model evaluated the relationship between the interaction of [18F]AZD4694 and [11C]PBR28 with Apathy scores. The model’s covariates were age, gender, education and diagnoses of the participants.ResultWe found a strong positive correlation between the interaction of [18F]AZD4694 and [11C]PBR28 with apathy. The most impacted regions were the medialfrontal cortex, in the superior portion and prefrontal cortex, as well as the anterior nucleus of the thalamus.ConclusionThese preliminary results corroborate the link between amyloid and neuroinflammation, that potentiating the neuropsychiatric symptom apathy. The regions impacted are involved in proper behavior, such as the mediofrontal cortex. This study supports previous findings showing that amyloid and neuroinflammation are related to apathy.
Science and biomarkers of vascular contributions to cognitive impairment and dementia (VCID)
Authors: Corriveau Roderick A. 
Published: December 2020

AbstractBackgroundThe scientific framework of vascular contributions to cognitive impairment and dementia (VCID) was introduced in 2013 in response to the fact that most individuals diagnosed with Alzheimer’s dementia also have cerebrovascular pathology. The science of VCID brings into focus the hypothesis that vascular lesions may be a cause of cognitive impairment and dementia that occurs independently or, much more frequently, in the absence of a vascular diagnosis and in combination with one or more other brain pathologies.MethodThe scope of VCID research is defined as the aging neurovascular unit integrating, and failing to cope with, biological insults due to vascular disease, proteinopathy including Alzheimer’s pathology, metabolic disease, and immune activity. Moreover, the direct role of each pathology, and other co‐morbidities, in causing dementia is the subject of hypotheses that must be rigorously tested to move toward successful interventions.ResultIn addition to better mechanistic and clinical understanding of VCID, which will result in targets, rigorously validated clinical trial ready VCID biomarkers have emerged as a critical priority for addressing the burden of dementia worldwide. Barriers include leveraging traditional research measures into bona fide clinical trial ready biomarkers, determining whether risk measures can provide sufficiently robust signals to serve as a valuable clinical biomarkers, and ensuring that VCID biomarkers that move forward are valid and useful for clinical trials and interventions across diverse populations as well as in populations that experience health disparities. Large scale efforts are underway to meet these goals to provide VCID biomarkers to promote effective clinical trial engagement in VCID.ConclusionBecause of the proven ability to prevent and treat cardiovascular disease and hypertension with population benefits for heart and stroke outcomes, it has now been proposed by many that understanding and targeting the biological mechanisms of VCID can have a similarly positive impact on public health. The development of VCID biomarkers is of critical importance in realizing this potential.
Selective loss of episodic memory of odor percepts is associated with progression to amnestic MCI or Alzheimer’s disease in cognitively healthy seniors
Authors: Albers Mark W , Albers Alefiya , Keim Abigail C , Cunin Camille , Hyman Bradley T , Gomez‐Isla Teresa , Blacker Deborah , Das Sudeshna , Locascio Joseph J 
Published: December 2020

AbstractBackgroundAccumulating evidence indicates that the pathological changes of AD begin 15 years prior to symptom onset. There is an unmet need for accessible, affordable, and accurate means to screen cognitively normal individuals for preclinical AD. We previously developed the Percepts of Odor Episodic Memory (POEM) test battery, which assesses identification, memory and discrimination of odor percepts. In a pilot study, we demonstrated that elderly individuals with odor memory scores that fell below the 50% confidence intervals of the memory scores predicted by their odor discrimination and odor identification scores; these individuals were deemed “at risk” for progression to mild cognitive impairment and AD based on an enrichment in biomarkers for AD.MethodWe tested our olfactory “at risk” status as a predictor of future decline by administering the POEM test battery to 61 older individuals who were cognitively normal (CN) or expressed subjective cognitive concerns (SCC) and were followed longitudinally in the Massachusetts Alzheimer’ s Disease Research Center. These individuals were added to our original sample of 140 participants who had undergone olfactory testing. A Cox Proportional Hazards model was used in a subset of this expanded cohort (n=127) who were followed over an average of 4.22 years to determine whether the olfactory “at risk” status predicted a risk of clinical progression to a diagnosis of amnestic MCI or Alzheimer’s disease.Result28% of the CN and SCC participants followed longitudinally were deemed “at risk” based on a selective odor memory loss. These “at risk” participants demonstrated a higher risk of progressing to amnestic MCI or AD (HR = 3.45, (95% CI:1.13‐10.72, p=0.0278) over time while controlling for age, education, and sex. The effect of Group (CN vs SCC) and its interaction with “at risk” status were not significant.ConclusionOur results indicate that probing olfactory function with a threshold based on personalized identification and discrimination abilities identifies cognitively healthy seniors who progress to amnestic MCI or AD at faster rate over time. Future work is focused on developing a remote version of this test for self‐administration that can be used to screen cognitively healthy individuals for research studies and clinical trials.
Baseline findings of the Filipino Multicomponent Intervention to Maintain Cognitive Performance among High‐Risk Populations (FINOMAIN) study
Authors: Moral Maria Clarissa Ora Del , Dominguez Jacqueline C , Phung Thien Kieu Thi , Guzman Ma Fe P , Moral Reizelle Marie O Del 
Published: December 2020

AbstractBackgroundFINOMAIN is an on‐going community study which integrates nutrition counselling (“the Philippine plate” or pinggang Pinoy), standard vascular care, and physical exercise in the form of a ballroom dance protocol known as INDAK (Improving Neurocognition through Dance and Kinesthetics). The multicomponent intervention will last for 48 weeks. Nutrition counselling and standard vascular care are given every third month, and INDAK is given twice a week for 60 minutes each session.MethodFINOMAIN is a two‐arm, single‐blind, cluster randomized controlled trial of a multicomponent intervention to prevent cognitive decline among at‐risk elderly. A total sample of 71 participants (intervention=38, control=33) from 8 community clusters in Quezon City, Metro Manila joined the pilot study. Baseline data included demographics, cognitive profile, behavioural and functional profile, anthropometric measures, and medical and laboratory measures.ResultThe comprehensive assessment included (1) cognitive measures (Clinical Dementia Rating‐Sum of Boxes, Alzheimer’s Disease Assessment Scale‐Cog, Alzheimer’s Disease 8, Montreal Cognitive Assessment‐Philippines, Mini Mental State Examination‐Philippines, Verbal Fluency [animal and vegetables categories], Digit Symbol Substitution Test, Trail Making Test A and B, Number Cancellation Task, Logical Memory [immediate recall, delayed recall, and recognition], Digit Span [forward and backward], and Boston Naming Test), (2) behavioural and functional measures (Neuropsychiatric Inventory, Geriatric Depression Scale, EQVAS Health‐Related Quality‐of‐Life, Lawton’s Instrumental Activities of Daily Living, Disability Assessment for Dementia, Time Up and Go, Sit to Stand Test, Grip strength, Tinetti Balance and Gait, and Berg Balance Scale), (3) anthropometric measures, and (4) medical and laboratory measures (lipid profile, cholesterol level, fasting blood glucose, vitamin B deficiency, osteoarthritis, anemia, depression episode history, alcohol use, smoking history, and blood amyloid [MDS‐AD test]). The intervention and control groups are comparable in all baseline measures (p’s>0.05). A random sample of 38 was drawn from 52 individuals who attended an 8‐week INDAK training, to compose the intervention group. Compliance to INDAK protocol was 97.4% (>/=80%).ConclusionFINOMAIN is a much‐needed study to confirm the efficacy of multicomponent interventions in preventing cognitive decline among at‐risk elderly in a community setting. Data can be compared with other multicomponent programmes to select the most effective interventions for specific at‐risk populations.
Associations between depression symptoms and executive function in older adults with mild cognitive impairment: One‐year follow‐up
Authors: Costa Mônica Vieira , Ávila Rafaela , Cintra Marco Túlio , Pires Lívia Rabelo , Pires Ricardo Lage Guerra Lott , de Paula Jonas Jardim , Bicalho Maria Aparecida 
Published: December 2020

AbstractBackgroundPsychiatric disorders are among etiologies for Mild Cognitive Impairment (MCI), one of the main one is depression. The relationship between depression and Alzheimer's disease (AD) is not yet fully understood and it is considered both, isolated risk factor and prodrome stage of AD. The aim of this work is to investigate if older adults with MCI associated with significant depressive symptoms, compared with those without these symptoms, will have different executive functions outcomes after one‐year follow‐up.MethodRepeated measures ANCOVA with Bonferroni post‐hoc analysis was used with cognitive variables at baseline and follow up evaluation as dependent, presence of significative depression symptoms at baseline as independent while controlling for covariates age, gender and years of formal education. Depressive symptoms were measured by 15‐item geriatric depression scale and the cutoff point was 6. Executive functions as inhibitory control e cognitive flexibility were assessed by Five Digit Test, working memory by Digit Span Test and phonemic verbal fluency by letter S. Patients started depression treatment at baseline.ResultWere included 170 participants (125 without depressive symptoms and 45 with symptoms), mean age 74.44, 68 women, mean years of formal education was 4,54. Among these, 99 (29 with depressive symptoms) complete all tests in the two assessments. Due to cognitive impairment, some of them were unable to even start cognitive flexibility test. Results indicated there was a significant effect of depression symptoms at baseline on cognitive flexibility ability [F (1.94) = 7,271, p = 0.008). Participants with depression presented a significant improvement (p = 0.006) on cognitive flexibility average from baseline (11.60) to the end of follow up (7.24). For those without symptoms of depression at baseline, the averages were 6.32 at baseline and 5.98 at follow‐up. There was no significant effect of depressive symptoms on the other cognitive skills assessed when considering these covariates.ConclusionComparing participants with and without depression symptoms at baseline, there was an improvement in cognitive flexibility in the former group. We think this result could be related to effect of depression treatment.
Tau deposition assessed by [18F]MK6240 PET is associated with longitudinal decrease in grey matter density across the spectrum of Alzheimer’s disease
Authors: Lussier Firoza Z. , Pascoal Tharick A. , Therriault Joseph , Tissot Cécile , Savard Mélissa , Benedet Andréa Lessa , Kang Min Su , Arias Jaime Fernandez , Wang Yi‐Ting , Mathotaarachchi Sulantha , Stevenson Jenna , Gauthier Serge , Rosa‐Neto Pedro 
Published: December 2020

AbstractBackgroundReduction in grey matter (GM) is a well‐established neuroimaging finding in Alzheimer’s disease (AD). Here, we sought to determine whether baseline tau‐PET using the high‐affinity tracer [18F]MK6240 is predictive of longitudinal changes in GM across the AD spectrum.MethodBaseline [18F]MK6240 PET data and longitudinal structural MRI was acquired for 79 participants in the TRIAD cohort (47 CN, 20 MCI, 12 AD). [18F]MK6240 standardized uptake value ratio (SUVR) were calculated 90‐110 minutes post‐injection using cerebellar GM as the reference region. T1‐weighted MR images were segmented into probabilistic GM and WM maps, which were non‐linearly registered to the ADNI template using DARTEL and smoothed with an 8mm FWHM Gaussian kernel. Voxel‐based morphometry (VBM) was run on GM and WM maps. Longitudinal changes in GM density were indexed by voxel‐wise percentage change in VBM‐derived GM. Voxel‐based regression analyses were conducted to examine associations between baseline [18F]MK6240 SUVR and change in GM density, with age, gender, years of education, diagnosis, and time interval between MRI acquisitions employed as covariates.ResultBaseline [18F]MK6240 SUVRs in Braak I/II, III/IV, and V/VI were significantly correlated with longitudinal decrease in GM density in the lateral and medial temporal lobe, including hippocampal regions. All results survived correction for multiple comparisons using random field theory at p < 0.001.ConclusionOur results suggest that tau pathology at baseline is associated with the progression of GM atrophy over time in brain regions vulnerable to AD pathological changes, providing evidence that tau‐PET may identify individuals who are more susceptible to atrophy.
Potentially inappropriate anticholinergic medication use interacts with memory‐enhancing treatment for patients with Alzheimer’s disease or related dementias
Authors: Vickers Lauren , Martinez Ashley I , Wallem Alexandra M , Moga Daniela C 
Published: December 2020

AbstractBackgroundAnticholinergic medications have been consistently linked to cognitive impairment or decline, resulting in their classification as potentially inappropriate medications for older adults according to the Beers Criteria. Despite their potential for adverse effects, these medications continue to be used for individuals regardless of their cognitive status and concurrent medications. Here, we investigated risk factors for anticholinergic medication use in populations with and without Alzheimer’s disease or related dementias (ADRD). For patients with ADRD, we also investigated whether anticholinergic use may be interacting with memory‐enhancing medication therapy.MethodsWe conducted a cross‐sectional study using nationally representative data from the 2016 National Ambulatory Medical Care Survey. We included non‐perioperative office‐based visits for patients ≥ 65 years old. Visit characteristics were compared between those with and without ADRD using descriptive statistics; adjusted logistic regression was used to identify predictors of anticholinergic use.ResultsOf 218,182,131 outpatient visits, 2.2% were for patients with ADRD (N=4,651,563). 20.5% of visits for patients with ADRD reported an anticholinergic, compared to 8.1% of visits for patients without ADRD. The most common anticholinergics reported for ADRD visits were cyclobenzaprine (25.3%), benztropine (12.8%), and meclizine (12.2%). Significant predictors of anticholinergic report (aOR [95% CI]) were ADRD status (3.1 [1.2‐8.3]), female sex (2.1 [1.4‐3.1]), new problem as primary visit reason (1.8 [1.2‐2.7]), former tobacco use (1.7 [1.1‐2.7]), and polypharmacy (11.6 [6.9‐19.7]), respectively). Of the 1,633,358 visits for patients with ADRD that reported use of a cholinesterase inhibitor, 29.3% also reported an anticholinergic, which combination may negate any cognitive benefits the cholinesterase inhibitor may have been able to impart.ConclusionIn a nationally representative sample, anticholinergic use was reported in approximately one‐fifth of visits for patients with ADRD. After adjusting for potential confounders, ADRD was an independent risk factor for report of an anticholinergic. Of those visits for ADRD patients whose cognitive impairment was being treated with a cholinesterase inhibitor, almost one‐third reported a drug‐drug interaction with an anticholinergic that may have detrimental results on cognition. Future work should investigate points of intervention to reduce anticholinergic use and inappropriate drug interactions in this population.
Improving Caregiving for Dementia (I‐CareD): Mobile health technology for dementia caregivers
Authors: Tan Zaldy S , Camarena Paul , Jennings Lee 
Published: December 2020

AbstractBackgroundMobile health applications represent a rapidly‐emerging technology that can improve health‐care delivery. Informal caregivers play an essential role in the care of persons with dementia; however, as a group dementia caregivers lack knowledge about the disease and available community‐based resources. Little is known about the acceptability and usefulness of mobile applications technology to provide information and resources to dementia caregivers.MethodThe I‐CareD app is a novel mobile application that provides dementia caregivers with information tailored to the care recipient’s dementia type and stage, behavioral issues, and needs for community‐based resources. Informal caregivers enrolled in a dementia care management program were provided instructions to downloaded the app.ResultThirteen caregivers completed a survey assessing information‐seeking behaviors/preferences and satisfaction with the app. The majority of caregivers were middle‐aged (50‐64 years; 54%), male (62%), white (83%), and college‐educated (54%). Most respondents (62%) provided care for persons with moderate‐stage dementia and 85% used a smartphone or tablet to search the web for health information. Ninety‐two percent of the caregivers preferred to receive dementia caregiving information electronically rather than by other means. The caregivers rated the app highly for ease‐of‐use, content and overall satisfaction. All of the caregivers who completed the survey stated that they would recommend the mobile app to other caregivers.ConclusionInformal caregivers were receptive to receiving dementia information and resources delivered via a mobile app. Although more research is needed to examine how to incorporate technology into dementia care, our study suggests that informal caregivers are likely to use technology that they perceive will help enhance their dementia caregiving.
Cerebrospinal fluid biomarker levels are not affected by aspiration or gravity drip extraction methods in Alzheimer’s disease: The AIBL study
Authors: Doecke James D , Francois Cindy , Fowler Christopher J , Stoops Erik , Rainey‐Smith Stephanie R , Li Qiao‐Xin , Masters Colin L , Martins Ralph N , Villemagne Victor LL , Vanderstichele Hugo Marcel 
Published: December 2020

AbstractBackgroundPrecise analysis of early changes in concentrations of proteins in cerebrospinal fluid (CSF) with qualified immunoassays can reflect the initiation or existence of Alzheimer’s Disease (AD) pathology in brains of affected subjects. Although CSF biomarkers are well established nowadays for use in clinical routine worldwide (eg. NIA AA guideline, FDA qualifications), there is still some ambiguity as to which method should be used to extract the CSF. We aimed to compare in detail potential differences on the most promising protein biomarkers between gravity or aspiration extraction of CSF.MethodsColorimetric ELISA immunoassays, developed by ADx NeuroSciences and commercialised by EUROMMUN, were used for the study. Our study assessed a panel of individual proteins (as well as their corresponding ratios) that are related to amyloidopathy (Aß1‐42, Aß1‐40), tauopathy (total tau), or synapse pathology (BACE1, Neurogranin Truncp75, a‐Synuclein). Concentration differences between using either gravity drip or aspiration extraction methods were evaluated in the same subjects in a sub‐population from the Australian Imaging, Biomarkers and Lifestyle (AIBL) study of ageing across. Subjects included in the study were cognitively normal (CN, N = 36), mild cognitive impairment (MCI, N = 8) or AD (N = 6). All analytes were tested by a single operator in parallel on the same day to minimize bias due to the test method and using manual test procedures.ResultsResults from statistical assessments confirm high concordance in biomarker levels between extraction methods (Concordance Correlation [CC] >0.85). Bland Altman plot analyses revealed an even symmetry around the zero‐difference line for each of the individual biomarkers and their corresponding ratios. Passing Bablock regression defined low beta coefficients indicating high scalability. Results were consistent across all three cognitive groups, irrespective of sample size.ConclusionsThe consistency in CSF biomarker levels across extraction methods demonstrates that the selection of the extraction method will not affect protein concentration analysis for respectively Aβ1‐42, Aβ1‐40, total tau, Neurogranin Truncp75, BACE‐1 and α‐synuclein). This new dataset will further help the field to better understand pre‐analytical factors of the discussed biomarkers, and prepare a final consensus guidance for collection, storage, and analysis of CSF.