bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perspectives on dementia care amongst primary care providers
Authors: Macchi Zachary A , Pressman Peter S 
Published: December 2020

AbstractBackgroundPersons with dementia require extensive medical and psychosocial support to delay progression and prolong functional independence. Early diagnosis improves quality of life, symptom management, and caregiver burden. Primary care providers (PCPs) are commonly the initial healthcare point of contact for individuals with dementia. However, there is a tendency towards under‐diagnosing dementia in the primary care setting and a majority of patients receive no formal diagnosis nor dementia type differentiation. Individuals with dementia also experience low rates of specialist referrals. Our aim is to describe the perspectives of PCPs regarding the management of dementia in order to identify areas for improving early dementia care delivery.MethodWe conducted a survey of 208 Internal Medicine PCPs practicing across three institutions in Denver, Colorado, including an academic hospital, Veterans Affairs system, and a local county hospital. A five‐point Likert scale was used to assess held views on clinical training, challenges of care compared to non‐neurologic illness (heart failure and diabetes), the PCP’s role in dementia care, screening and diagnosis, resources for referral, and barriers to care coordination.ResultsA total of 26 providers responded at a rate of 12.5%. Additional training in: triggers for referral, care plan formulation, and behavioral symptom management were identified as helpful to these providers. A number of responders strongly agreed that dementia care was challenging (37.5%, r2 =0.44, SD=0.66) compared to managing heart failure or diabetes (r2 =0.83, SD=0.91). PCPs reported a lack of referral resources (45.8%), difficulties in care coordination (41.7%) and minimally agreed with the statement that there “are effective ways to manage dementia” (79.1%). The biggest barriers to dementia care delivery were “inadequate time” (r2 =1.17, SD=1.08) and “inadequate resources for ongoing care” (r2 =0.80, SD=0.89).ConclusionPCP viewpoints on the challenges of dementia care, but perceived lack of effective management strategies, suggest a disconnect between clinical practice and evidence showing the benefits of comprehensive dementia care. Access to specialists (e.g. neurologists, geriatricians) might improve dementia care by improving allocation of dementia support resources. Our response rate is consistent with published, disincentivized surveys of PCPs.
Identifying mild cognitive impairment with older aboriginal Australians in community settings: Performance of the Clock Drawing Test relative to other cognitive screening tools
Authors: Nichols Madeleine , Lavrencic Louise , Radford Kylie 
Published: December 2020

AbstractBackgroundThe Clock Drawing Test (CDT) is commonly used in the detection of cognitive disorder. Easily administered in both clinical and non‐clinical settings and well accepted by patients, this test is a good candidate for use in early detection of dementia with older Aboriginal Australians. This study aimed to: (i) compare three CDT scoring methods and their reliability/validity in detecting mild cognitive impairment (MCI) and dementia in Aboriginal communities; (ii) determine the optimal CDT sensitivity, specificity and cut‐off scores; (iii) investigate the relative and combined performance of the CDT with other cognitive screening tools [Kimberly Indigenous Cognitive Assessment (KICA); Mini Mental State Examination (MMSE); Rowland Universal Dementia Assessment Scale (RUDAS)].MethodA subset of participants (n=153; aged 60‐93) recruited for the Koori Growing Old Well Study completed neurocognitive evaluation as part of a comprehensive medical assessment and were diagnosed by expert consensus as intact, MCI or dementia. CDT responses originally scored as part of the Addenbrooke’s Cognitive Examination Revised (ACE‐R) were rescored using the Mendez and Sunderland methods by an assessor blind to diagnosis.ResultThere were strong positive correlations between all three CDT scoring methods (r
s
range=.895‐.924). All methods differentiated dementia from MCI and intact participants (p<.001), but not intact from MCI (Mendez p=.712; Sunderland p=.545; ACE‐R p=.094). There was no significant difference between scoring methods in diagnostic validity for dementia (AUC=.739‐.756); however, the simple ACE‐R method had the highest positive and negative predictive values (PPV=0.643; NPV=0.862), with optimal cut‐off score <3.The MMSE outperformed all other screening tests in detecting cognitive impairment (MCI or dementia; AUC=.851) and was superior to both the KICA and CDT in distinguishing MCI from intact participants, but comparable to the RUDAS. Combining the CDT with other screening tools did not significantly improve their diagnostic performance for either cognitive impairment or MCI.ConclusionCDT alone is not an adequate screening tool for MCI; however, has potential for detecting moderate to severe cognitive impairment in older Aboriginal Australians. Relative to other screening tools, the MMSE performed well for detecting both cognitive impairment and MCI; the addition of the CDT did not significantly improve other tests’ performance.
Role of apolipoprotein ε4 allele as a predictor in the course and outcome in patients with subcortical vascular dementia
Authors: Issac Thomas Gregor , PT Sivakumar , Chandra S.R. , Christopher Rita , Rajan Jamuna G. , Philip Mariamma , Clinic Geriatric ,   Services, NIMHANS, India
Published: December 2020

AbstractBackgroundVascular dementia (VaD) is the second most common dementia in elderly and the major contributor being Cerebral Small Vessel Disease (SVD) which has radiological manifestations of White Matter Hyperintensities(WMH), Cerebral Microbleeds and Lacunar infarcts. This study looks into the role of clinico‐demographic profile, genetic factors in terms of Apo E4 status and neuropsychological characteristics in predicting the course and outcome in patients with Subcortical VaD.MethodA prospective cohort study involving 202 patients who were followed up at baseline and subsequently after 1 and 2 years’ time intervals following informed consent and IEC approval with attempt to understand the role of APOE4 positive status as a predictor for cognitive decline. Comparison of Neuropsychological test performance with ANOVA, regression analysis and survival analysis by plotting Kaplan Meier’s curve was done using SPSS v.21.ResultThe major risk factor identified was Hypertension in 92% followed by smoking in 76% and low socioeconomic status in 56% patients. 35.7% of the population had an APO E4 allele positivity. Regression analysis done showed APO E4 positive status as a significant independent predictor of poorer performance in neuropsychological test scores across time periods. However, survival analysis utilizing Kaplan Meir’s plot showed that unlike smoking and WMH (Odds ratio : 2.62) which increased mortality rates more than twofold, APO E4 did not contribute to increased mortality.ConclusionThis study comprehensively looks into the role of APO E4 in VaD and identifies need for prevention of modifiable risk factors like smoking, hypertension, low SES, poor cognitive reserves and WMH which predicts cognitive decline in subcortical VaD and lead to early mortality in patients with VaD. Positive APO E4 allele status significantly affects performance in cognitive assessments but does not appear to predict mortality and hence risk modification needs to be tailored in patients with VaD.
Fukushimura BrainBank project, Japan
Authors: Kaneda Daita , Akatsu Hiroyasu , Ogawa Norihiro , Kanesaka Takeshi , Hishida Chie , Yamamoto Sakon , Yamamoto Takayuki , Yoshio Hashizume 
Published: December 2020

AbstractBackgroundThe Fukushimura (welfare village), located in Toyohashi city, Japan, is a unique complex of various nursing home facilities including dementia homes, Day‐care houses, homes for disabled and mentally retarded, and the Fukushimura Hospital. This village is totally managed by private sector, the Sawarabi Medical Cooperative. About 800 elderly people reside in this area. The hospital plays a pivotal role within the village and acts as the central facility for each nursing homes. Fukushimura BrainBank (FBB) was established in 1990. The neuropathological investigation of FBB was initially conducted by Kenji Kosaka, who initially reported cortical Lewy bodies. Our research institute was approved in 2004 by the Ministry of Education, Culture, Sports, Science and Technology, as one of the non‐governmental institutes which is permitted to apply for governmental grants.MethodFor collecting CNS specimens, the brains are separated into two hemispheres, one for neuropathological analyses with using several antibodies for beta‐amyloid, phosphorylated tau, alpha‐synuclein, and TDP‐43. Modified gallyas‐silver staining is applied for evaluating argyrophilic grain disease. The other hemispheres are stored for frozen sections. All the medical records and radiological images from the nursing home to hospital are stored in the research institute, which make it possible for the researchers to access the psychological symptoms observed by carers in the long duration of the disease.ResultThe number of autopsy became over 30 cases per year. Most of the patients had dementia or chronic devastating cerebrovascular diseases. Of note, geriatric residents with mentally retardation or cerebral palsy from childhood were included. At the end of 2019, more than 720 of frozen brains with detailed medical record are stored in FBB and readily available for research. The neuropathology database share the same coding system for Japanese Brain Bank Network for Neuroscience Research (JBBNNR). We already have over 20 collaborators and supply our samples for more than 30 research institutes in Japan.ConclusionThe challenge of FBB will play a unique and important role to clarify cliniconeuropathological correlation of the nursing home residential with various geriatric conditions, especially from the point of view of nursing staffs.
Multimodal imaging reveals human cholinergic system functional and structural integrity in vivo
Authors: Nemy Milan , Grothe Michel , Barroso Jose , Teipel Stefan J. , Westman Eric , Ferreira Daniel 
Published: December 2020

AbstractBackgroundRecent advances in the neuroimaging field have rekindled the interest for the human cholinergic system. As the widespread projections from the basal forebrain to the cortex play an important role in learning, memory and other cognitive processes that are significantly impaired in disorders such as Alzheimer’s disease, Dementia with Lewy Bodies, and Vascular Dementia, it is favourable to assess the affected pathways and cortical regions in vivo. However, research is still limited and different imaging modalities need to be combined to advance our current understanding of the complex interplay between anatomical, functional and physiological features of the human brain cholinergic system. We developed an advanced framework using deterministic fibre‐tracking methods using diffusion‐tensor imaging (DTI), and partitioning of the human basal forebrain on T1‐weighted structural MRI data supported by resting‐state functional MRI (rs‐fMRI) data.MethodA total of 197 cognitively healthy individuals were recruited. The rs‐fMRI, DTI, and T1 data were processed with MRtrix3, DPARSFA, and SPM12 in order to track pathways rising from basal forebrain subdivisions towards rs‐fMRI identified cortical areas.ResultWe identified two functionally relevant subdivisions of the basal forebrain by clustering based on functional connectivity characteristics. The resulting subdivisions resemble cytoarchitectonically defined subdivisions as revealed by stereotactic mappings. Distinct white matter tracts originated from individual basal forebrain subdivisions towards cortical cholinergic areas, each of which showed differential associations with relevant cognitive functions.ConclusionHere we present a novel method of combination of MRI‐based techniques to assess and visualize the human cholinergic system in vivo. The ability to functionally subdivide the basal forebrain and model cognitive‐specific cholinergic pathways and cortical cholinergic areas opens new opportunities to investigate Alzheimer's disease and other neurodegenerative diseases with cholinergic involvement, with possible diagnostic and prognostic use.
APOE and sex‐stratified genome‐wide meta‐analyses of Alzheimer’s disease
Authors: Sáez María Eugenia , Moreno‐Grau Sonia , Madrid Laura , Ramirez Alfredo , Ried Janina S. , González‐Pérez Antonio , Ruiz Agustín ,   GR@ACE/DEGESCO Consortium, CHARGE Consortium, GERAD Consortium
Published: December 2020

AbstractBackgroundGenome‐wide studies have identified diverse susceptibility genes for Alzheimer’s disease, with the APOE locus being the major risk factor known so far. However, pathogenic mechanisms and the influence of other known AD loci or patient characteristics such as gender have been poorly explored. The ADAPTED IMI consortium, focused on exploring the APOE biology, has conducted the first genome‐wide meta‐analysis of AD stratified according to the three main APOE haplotypes. Additionally, we also explored the effect of gender on AD by performing sex‐stratified meta‐analysis.MethodsAPOE stratified meta‐analysis was performed in three stages comprising 39,186 human samples from sixteen datasets including ADNI, AddNeuroMed, ADGC, Mayo, Neocodex‐Murcia, NIA, ROSMAP, TGEN study for Stage I, GR@ACE and GERAD for Stage II and ARIC, CHS, FHS and RS (CHARGE consortium) for Stage III. Sex‐stratified meta‐analysis was performed on Stage I and Stage II datasets.After quality control and imputation, association of genotype dosages with the AD case‐control status for each dataset was investigated through regression models adjusted by age, sex and the first four PC vectors, plus APOE status in the sex stratified analysis. Meta‐analysis was performed using the inverse variance weighing method. Results were summarized on gene‐level and explored for enrichment in known pathways and processes.ResultsIn the combined analysis, we identified genome‐wide significant signals for APOE, BIN1, CLU, PICALM and a large intergenic region in 4p15 in the APOE ε4 stratum, and for ABCA7, BIN1 and PICALM in the APOE ε3 stratum, whereas no genome‐wide significant results were found in the APOE ε2 stratum. Sex‐stratified analysis identified genome‐wide significant signals for BIN1 and APOE as well as suggestive signals for PICALM, MYLK, SOX5 and SCEL in the female stratum. By contrast in males, only suggestive signals for BIN1, APOE, ZCCHC2, the ABI3BP/IMPG2 locus, ESRRB and the 19q13.4 leukocyte receptor cluster were identified. Accordingly, APOE‐ and sex‐specific pathways were highlighted.ConclusionsThis systematic stratified analysis led to the identification of loci associated with AD risk, which are specific for certain APOE haplotypes and specific combinations of APOE haplotypes and gender. This novel insight contributes to unravel the complex architecture of AD pathology.
Associations of dietary patterns and CSF biomarkers for Alzheimer’s disease in a population‐based sample of 70‐year‐olds
Authors: Samuelsson Jessica , Kern Silke , Zetterberg Henrik , Blennow Kaj , Rothenberg Elisabet , Wallengren Ola , Skoog Ingmar , Zettergren Anna 
Published: December 2020

AbstractBackgroundDiet could be a modifiable factor in the prevention of Alzheimer’s disease (AD). Western‐style dietary patterns are considered to increase the risk, while Mediterranean‐style dietary patterns are considered protective. The aim of this study was to investigate the relation between dietary patterns and CSF biomarkers of relevance for AD.MethodData was derived from the population based Gothenburg H70 Birth Cohort Studies, Sweden (n=1203). CSF levels of β‐amyloid (Aβ)42, total tau, and phosphorylated tau were measured with ELISA. Dietary intake was determined by the diet history method (n=861). Principal component analysis were performed to reduce 21 food groups into factors representing dietary patterns. Logistic regression analyses, with CSF biomarkers as dependent variables (pathological, yes/no), and linear regression analyses with CSF biomarkers as continuous variables, were performed on the dementia‐free participants with both CSF and dietary data (n=269, 49% women). Analyses were adjusted for APOE ε4 status, energy intake, education, BMI and physical activity and sex. Analyses were also performed stratified by sex.ResultFour dietary patterns were derived from the principal component analysis. A western‐style dietary pattern, a Mediterranean‐style dietary pattern, a mixed dietary pattern with alcoholic beverages and a dietary pattern of high fat dairy products, eggs and refined cereal products. The odds ratio of having pathological values of total tau was higher among those with a higher compliance to a western‐style dietary pattern (OR 1.37; 95%CI 1.02‐1.85). The linear regression model indicate the same trend (r2=0.06, B=0.04, p=0.08). When stratified by sex, the odds ratio of having pathological values of phosphorylated tau was higher for men with a higher intake of high fat dairy products, eggs and refined cereal products (OR 3.38; 95%CI 1.22‐9.36). There were no associations between the other dietary patterns and CSF biomarkers.ConclusionOur results indicate an association between western‐style dietary patterns and increased levels of total tau and phosphorylated tau. There was no relation between a healthier Mediterranean‐style dietary pattern and CSF biomarkers for AD, however.
Sulcal morphology as predictor of cognitive decline over a 3‐year period in elderly at risk to develop Alzheimer’s disease
Authors: Mortamais Marion , Gutierrez Laure Anne , Balem Marianne , Bars Emmanuelle Le , de Champfleur Nicolas Menjot , Bouyahia Ali , Chupin Marie , Perus Lisa , Fischer Clara , Vellas Bruno , Andrieu Sandrine , Mangin Jean‐Francois , Berr Claudine , Gabelle Audrey ,   MAPT/DSA study group
Published: December 2020

AbstractBackgroundCerebral sulci openings have been consistently observed as larger in Alzheimer’s disease (AD) patients than in cognitively normal elderly. However, it remains unknown whether large openings may have predictive value of cognitive trajectories. We aimed to determine whether sulci openings might be predictors of changes in cognition over a 3‐year period in elderly people at risk to develop AD (at‐AD‐risk).MethodParticipants were recruited in memory and research centers in France between 2008 and 2011 in the framework of the MRI‐Multidomain Alzheimer Preventive Trial (MRI‐MAPT) ancillary study. They were non‐demented community‐dwelling women and men aged ≥ 70 years, and presented memory complaints and frailty criteria. In 20 sulci distributed throughout the brain, openings were extracted from Magnetic Resonance Imaging (MRI) T1‐weighted images obtained at baseline in 433 participants, using the Morphologist pipeline of BrainVISA [http://brainvisa.info, version 4.5.1]. Cognition was evaluated at baseline, 6, 12, 24, and 36 months of follow‐up with a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini‐Mental State Examination (MMSE) orientation items, Digit Symbol Substitution Test, and Category Naming Test). Linear mixed regression models explored the composite score variation over time according to the baseline openings magnitude.ResultAt baseline, participants were on average 74.8 (4.0) years old. The mean MMSE was 28.1 (1.5) and the mean composite cognitive score was 0.11 (0.62). Sulci openings were categorized into tertiles (T1, T2, T3) for the statistical analyses. The participants showing the largest openings (T3) in the left anterior inferior temporal sulcus presented a greater decline in the composite cognitive score over the 3‐year period of follow‐up (β=‐0.07, 95%CI [‐0.12; ‐0.02]) than the participants with lower openings values.ConclusionLarge openings of sulci within the lateral temporal area of the brain might be predictors of cognitive decline within 3 years in at‐AD risk individuals. These results may have strong applications in clinical setting and for preventive strategies.
Interneuron hyperexcitability as both causal factor and risk factor in Alzheimer’s disease
Authors: Hijazi Sara , Heistek Tim , Scheltens Philip , Mansvelder Huibert D. , Smit August B. , van Kesteren Ronald E. 
Published: December 2020

AbstractBackgroundNeuronal network dysfunction is increasingly recognized as an early sign of Alzheimer’s disease (AD). This is seen for instance as neuronal hyperexcitability, a disturbance of excitation/inhibition balance and altered oscillatory activity and synchrony, both in patients and in mouse models of AD. The causes and functional implications of these network alterations are currently only starting to be revealed.MethodsWe tested the contribution of hippocampal parvalbumin‐positive interneurons to early neuronal network dysfunction in an APP/PS1 mouse model of AD. Patch clamp analysis was performed to measure neuronal excitability and synaptic connectivity. Chemogenetics was used to specifically restore PV cell excitability in APP/PS1 mice, or induce PV cell hyperexcitability in wildtype mice. A Morris water maze test was used to determine the consequences of these manipulations for learning and memory.ResultsWe found that hippocampal PV interneurons become hyperexcitable in APP/PS1 mice at an early disease stage, at 3‐4 months of age. Reducing PV cell excitability restores neuronal network properties and rescues learning and memory deficits. These effects are long‐lasting and are paralleled by a significant reduction in soluble amyloid‐beta concentrations and amyloid plaque load. Conversely, when we chemogenetically induced PV cell hyperexcitability in wildtype mice, animals developed network dysfunction and learning and memory impairments similar as observed in APP/PS1 mice. Interestingly, these impairments were transient, but could be reinstated by a singly low‐dose injection of amyloid‐beta directly into the hippocampus.ConclusionHippocampal PV interneuron hyperexcitability is an early phenomenon in APP/PS1 mice and causally contributes to the development of other AD‐like symptoms, such as neuronal network dysfunction, cognitive impairment and amyloid pathology. Interestingly, hyperexcitable PV neurons also renders healthy hippocampal circuitry vulnerable to amyloid‐beta‐induced toxicity. These findings thus establish PV cell hyperexcitability as both a causal factor and a risk factor in AD.