bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of a latent dementia index in the Aging, Demographics, and Memory Study
Authors: Saenz Joseph , Beam Christopher R 
Published: December 2020

AbstractBackgroundLongitudinal studies of aging often lack clinical gold standard measures of dementia and instead rely on nondiagnostic approaches to categorizing study participants as demented or cognitively normal. Recently, latent variable models have been used to estimate latent dementia indexes (LDI) using cognitive ability, memory, and functional ability measures to distinguish dementia risk from general cognitive functioning. The LDI exhibits clinical utility and puts dementia risk on a continuous scale, to approximate the process of becoming demented. The purpose of the current study is to validate an LDI in the Aging, Demographics, and Memory Study (ADAMS) using participants’ neuropsychological assessment and functional ability scores.MethodWe evaluated the 2001‐2003 ADAMS including 856 adults age 65+ who had participated in the United States Health and Retirement Study (HRS). ADAMS respondents were given an extensive neuropsychological battery of tests spanning various cognitive domains and provided information on functional abilities. We analyzed cognitive tasks (trails A&B, digits forward/backward, Shipley VocabularyTest, delayed 10‐word recall, recognition memory, and logical memory) and functional tasks (difficulty with household tasks, using familiar appliances, shopping independently, ability with complicated tasks, and handling small sums of money). Using confirmatory factor analysis, we modeled the LDI by performance on cognitive, memory, and functional ability reports. Validation involved comparing the LDI to the diagnosis of dementia made by a consensus panel including neuropsychologists, neurologists, geropsychiatrists, and internists.ResultsA single factor LDI model fit the data well (Comparative Fit Index = .96; Root Mean Square Error of Approximation = .05, .90CI: [.03, .06]). The LDI significantly predicted clinical gold standard diagnosis (OR = .55, .95CI = [.50, .60]), with LDI scores +1 SD above the LDI mean predicting .36 times lower odds of dementia and LDI scores ‐1 SD below the mean predicting 2.78 times greater odds of dementia.ConclusionAn LDI that does not rely on clinical gold standard dementia diagnoses has good clinical utility in the ADAMS 2001‐2003 sample. Future research includes validating LDI scores longitudinally in ADAMS and extending the LDI approach to the HRS core sample.
Community‐based participatory approach to promote convenience stores’ support for older adults with dementia in Japan
Authors: Igarashi Ayumi , Matsumoto Hiroshige , Takaoka Manami , Kugai Haruna , Suzuki Miho , Murata Satoshi , Shimada Hiromi , Kubo Tomoko , Hiratsuka Tomoyuki , Yazawa Akio , Yamamoto‐Mitani Noriko 
Published: December 2020

AbstractBackgroundConvenience stores (CVSs), small retail chains that sell a variety of daily necessities ranging from sandwiches to shaving creams in a neighborhood, support older adults with dementia by providing them a convenient shopping place and meeting their small daily needs. Since 2017, we have conducted community‐based participatory research in Nerima City, Tokyo, to promote collaboration between CVSs and community healthcare/social care professionals and to strengthen the CVSs’ support function for community‐dwelling older adults. We evaluated the effect of our activities in the past 3 years.MethodsIn 2018, community support center (CSC) staff visited CVSs in the neighborhood to become acquainted with each other. Thereafter, the CSC staff continued to collaborate with CVSs in supporting older adults, such as by regularly asking the CVSs about difficulties in dealing with older customers. To evaluate these activities, every year from 2017 to 2019, we administered self‐report questionnaires to owners/managers of all convenience stores in Nerima City (intervention group) and two other cities (control group) in Tokyo. We analyzed the data using the difference‐in‐difference method.ResultsThe participants who completed the survey were 97 (valid response rate: 17.9%; n = 37 in Nerima vs. 60 in others) in 2017, 103 (19.2%; n = 50 vs. 53) in 2018, and 108 (17.9%; n = 52 vs. 56) in 2019. Altogether, the mean age (± standard deviation) was 46.9 (±13.0) years, and 77% were men; 56% were owners of the CVSs, and they had 17.1 (±7.2) staff in their stores. The analyses showed significant improvements in “experience of emergency protection for an older adult” (p = 0.03), “knowledge of the function of the CSC” (p = 0.001), “knowing individual healthcare/social care professionals in the CSC” (p = 0.02), and “awareness of when to contact the CSC” (p = 0.002) among the subjects in Nerima City as compared to those in other cities.ConclusionThe results suggest that these collaborative actions were effective in promoting activities to support older adults and establishing relationships between CVSs and CSCs.
Functional connectivity for discrimination between mild cognitive impairment and subjective cognitive decline in Alzheimer disease: A study on resting‐state EEG rhythms in the Peruvian population
Authors: Vilca Brenda Nadia Chino , Fernández Ricardo Bruña , Maestú Fernando , Acobo Roxana Castillo 
Published: December 2020

AbstractBackgroundThe increase in cases of dementia worldwide has promoted the development of research for its detection and early intervention. However, the strategies, procedures, and tools designed to address the problem from the international level have found significant barriers in its implementation in Latin American countries, where factors such as socio‐demographic variability and clinical techniques limit their scope in terms of identification and intervention. Under this framework, research with signals in EEG / MEG has shown that the analysis of functional connectivity can be a sensitive biomarker in neurodegenerative processes, including the analysis of pre‐symptomatic stages with subsequent conversion to Alzheimer disease. This study seeks to develop robust methods for the diagnosis and characterization of Alzheimer's disease (AD) in the phase from the analysis of 160‐channel EEG signals in the Peruvian population.Method500 screening evaluations were carried out, with 75 adults/seniors between 50 and 75 years of age being selected: 17 subjective cognitive declines, 24 with a family history of dementia and 31 mild cognitive impairment. The participants underwent four evaluation sessions, which included an EEG record in a state of rest (eyes closed and eyes open) and neuropsychological tests.ResultThe functional connectivity patterns are consistent with similar studies using MEG in European and North‐American population.ConclusionOur results demonstrate the utility of the EEG for the diagnosis and distinction of the previous stages of AD and the variation of the default mode network between QSM, DCL, and AF.
Regulation of ribosomal function by oligomeric tau
Authors: Jiang Lulu , Wolozin Benjamin 
Published: December 2020

AbstractBackgroundAccumulation of tau pathology is a core feature of Alzheimer’s disease (AD) and related tauopathies, but tau pathology is pleiotropic. The many species of tau oligomers/aggregates has prevented elucidation of the mechanisms by which tau induces neurodegeneration. Fibrillary tau aggregates are considered to be less toxic than tau oligomers, but have received extensive attention because they are readily identifiable with pathological dyes, such as thioflavines, as well as by reagents used for diagnostic imaging. Multiple studies indicate that oligomeric tau (oTau) is the key toxic species, but the mechanism of toxicity is unknownMethodsWe applied optogenetics to induce tau oligomerization, and then used this to investigate the proteins with which oligomeric tau interacts and the mechanisms through which it regulates protein synthesis.ResultsOur results demonstrate a temporal evolution of oTau, transitioning from reversible to irreversible states. Tau oligomerization rapidly induces a translational stress response including inhibition of protein synthesis. Application of mass spectrometry identifies numerous ribosomal proteins that selectively bind to oTau. These ribosomal function appear to function in quality control of ribosome biogenesis and quality control of RNA translation.ConclusionoTau induces major changes in ribosomal function that alter quality control mechanisms related to ribosomal biogenesis and RNA translation.
Presentation 3: Translational dysregulation promotes pathogenic events in tauopathies
Authors: Koren Shon , Meier Shelby E , Abisambra Jose F. 
Published: December 2020

AbstractBackgroundA major challenge in the field of tau‐associated neurodegeneration is the identification of the pathogenic mechanisms leading to disease. Tau is best known for associating and stabilizing microtubules; however, emerging results identifying alternate tau functions opens a new opportunity to understand the molecular basis of disease. Given the association of tau with ribosomes and RNA, and the enhancement of this interaction in Alzheimer’s disease, we hypothesized that the aberrant tau‐ribosome interaction impairs (increases and decreases) transcripts that are necessary for cellular homeostasis. For nearly thirty years, the consequences of tau‐ribosome complexes were unknown until now.MethodsWe used in vitro models such as GFP‐based cell‐free translation assays and surface sensing of translation (SUnSET) assays in immortalized and primary neuronal cultures. Moreover, we pioneered in vivo SUnSET in the brains of tau transgenic mice, and coupled these techniques with proteomics. We validated our results using human brain samples from AD and non‐demented controls. Finally, we performed ribosomal profiling assays using in vitro models of tauopathy.ResultsWe demonstrate that pathological tau species associate robustly with ribosomes profoundly shifting the translatome. Surprisingly, a significant number of proteins whose translation was impaired corresponded to ribosomal proteins. We also identified that the ribosomal protein S6, which regulates translation of the machinery necessary for translation (ribosomal proteins as well as elongation and initiation factors), was significantly reduced in vitro, in vivo, and in human brains. Finally, we also found major shifts in the integrity of AD brain polysomes as a consequence of tau aggregation.ConclusionPathological tau species negatively regulate ribosomal specificity thereby shifting the translatome.
A phase 1B open‐labelled study of sodium selenate as a disease modifying treatment for possible behavioural variant fronto‐temporal dementia
Authors: Vivash Lucy E. , Malpas Charles B. , Velakoulis Dennis , O’Brien Terence 
Published: December 2020

AbstractBackgroundThere are currently no approved disease‐modifying treatments of behavioural variant frontotemporal dementia (bvFTD), with the only treatments available providing symptomatic relief to secondary behavioural symptoms. Approximately 45% of bvFTD cases are tauopathies, with the main pathological hallmark and proposed pathogenic mechanism being the accumulation and aggregation of hyperphosphorylated tau. For this reason, hyperphosphorylated tau represents a promising target for a disease modifying treatment in this population. Sodium selenate stimulates the PP2A enzyme, which directly dephosphorylates hyperphosphorylated tau. This study investigated the use of sodium selenate as a disease‐modifying treatment for patients with bvFTD.MethodFifteen patients with possible bvFTD were treated with sodium selenate (15mg tds) for twelve months. Participants underwent a battery of cognitive and behavioural tests, MRI, lumbar puncture and safety assessments at screening, baseline, and at regular intervals following the commencement of treatment. Adverse events were monitored via diary cards between clinic visits.ResultFourteen patients are either on treatment or have completed the study. Interim safety analysis (9 completed patients, 5 on treatment) has shown that sodium selenate is safe and well tolerated, with no study withdrawals. Commonly reported adverse events are nail changes (n=5), fatigue (n=4) and nausea (n=4). No treatment related serious adverse events have occurred. An interim mixed‐effects analysis on all available neurocognitive data showed no statistically significant change in NUCOG total score (b=‐0.02, 95% CI = ‐0.18, 0.14]) or Carer Burden Scale (CBS) score (b =0.04, 95% CI = ‐0.05, 0.13]), CVLT total learning score (M diff = 5.80, 95% CI = ‐6.97, 18.57]), or NIH composite score (M diff = 4.72, 95%CI = ‐11.50, 14.70]). Percentage change in whole‐brain volume from baseline to 12 months ranged from ‐0.68% to ‐6.26% (n=5 <‐2%, n=2 ‐5‐6%).ConclusionThe interim results have shown that sodium selenate is safe and well tolerated in patients with bvFTD. Early indications show sodium selenate may be effective in reducing atrophy and halting cognitive decline in a subset of bvFTD patients. A larger phase 2 placebo controlled study is necessary to evaluate whether sodium selenate is efficacious as a disease modifying treatment of bvFTD.
Metabolic syndrome is associated with plasma β‐amyloid levels in ApoE ε4 non‐carriers
Authors: Dang Liangjun , Gao Ling , Shang Suhang , Chen Chen , Wei Shan , Wang Jin , Huo Kang , Wang Jingyi , Qu Qiumin 
Published: December 2020

AbstractBackgroundThe relationship between metabolic syndrome (MetS) and Alzheimer’s disease (AD) is not fully understood. As Amyloid‐β (Aβ) deposition in the brain is a main pathophysiology of AD and plasma Aβ is closely related to Aβ deposition in the brain, in present study, we investigated the relationship between plasma Aβ and MetS in community population.MethodThis was a population‐based cross‐sectional study. A total of 1275 participants from a village in the suburbs of Xi’an, China were enrolled from October 2014 to March 2015. Fasting venous blood was taken in the morning and plasma Aβ levels were measured by ELISA. The ApoE genotype was detected using polymerase chain reaction and Sanger sequencing. Metabolic syndrome was diagnosed according to ATP‐III riteria, and MetS severity z scores (MetS‐Z) were calculated from waist circumference, triglycerides, HDL cholesterol, systolic blood pressure, and fasting glucose. Relationships between plasma Aβ and MetS were determined using multiple linear regressions.ResultIn the total population and the ApoE ε4 non‐carriers, MetS was associated with higher plasma Aβ40 level (51.704±8.594 pg/ml vs. 53.536±8.063pg/ml, p=0.002;51.693±8.626 pg/ml vs. 53.593±7.990 pg/ml, p=0.003) and lower Aβ42/ Aβ40 ratio(0.814±0.189 vs 0.784±0.170, p=0.018;0.813±0.189 vs. 0.778±0.172, p=0.011). In the multivariable regression analysis, plasma Aβ40 was associated with MetS in the total population and ApoE ε4 non‐carriers (β=1.711, p=0.008; β=1.661, p=0.019) and Aβ42/ Aβ40 ratio (β=‐0.031, p=0.030; β=‐0.035, p=0.024). Furthermore, plasma Aβ40 correlated positively with MetS‐Z in the total population (r=0.073, p=0.009) and the ApoE ε4 non‐carriers (r=0.074, p=0.015), while Aβ42/Aβ40 ratio was negatively related with MetS (r=‐0.064, p=0.038) in ApoE ε4 non‐carriers, but not in ApoE ε4 carriers. There was no significant correlation between MetS and plasma Aβ42.ConclusionMetabolic syndrome was associated with higher plasma Aβ40 level and lower Aβ42/ Aβ40 ratio in ApoE ε4 non‐carriers, but not in ApoE ε4 carriers. This indicated that the relationships between MetS and plasma Aβ may be confounded by ApoE ε4 status.
fNIRS assessment during cognitive tasks in elderly patients with depressive symptoms
Authors: Kang Min Ju , Yang Youngsoon 
Published: December 2020

AbstractBackgroundThe aim of this study was to analyze and compare the level of activation in the frontal cortex using functional near‐infrared spectroscopy (fNIRS) according to the presence of depressive symptoms, which was assessed by the Geriatric Depression Scale (GDS) in elderly participants.MethodWe investigated 204 community‐based normal participants without psychiatric disorder or dementia between the ages of 60‐80 years. GDS and fNIRS were used to assess the presence of depression in all patients, along with cognitive tasks including the digit span, Verbal Fluency Task (VFT), and Stroop test to investigate hemodynamic response in the frontal cortex.ResultDuring the Stroop test, significantly reduced hemodynamics was observed in the depressive‐symptom group. Mean accΔHbO2 of all channel averages was 0.14μM in the control group and ‐0.75μM in the depressive‐symptom group (p=0.03), right hemisphere average was 0.13μM and ‐0.96μM, respectively (p=0.02), and left hemisphere average was 0.14μM and ‐0.54μM, respectively (p=0.12). There was no significant difference in hemodynamic response (mean accΔHbO2) between the two groups during the digit span backwards and VFT.ConclusionThe hemodynamic response during fNIRS was significantly different between control and depressive‐symptom groups. Among the three tasks, the Stroop test results indicated reduced hemodynamics in the frontal cortex of the depressive‐symptom group.
Influence of sleep quality, risk of obstructive sleep apnea and sleep deprivation on cortical oxygenation in elderly individuals
Authors: Bae Heewon , Kang Min Ju , Yang Youngsoon 
Published: December 2020

AbstractBackgroundPoor sleep quality, obstructive sleep apnea (OSA) and sleep deprivation are risk factors for cardiovascular diseases and cognitive impairment. Cerebral blood flow and its regulation are affected by pathological condition commonly observed in the elder population, such as dementia, history of stroke, diabetes mellitus and hypertension. The aim of this study was to investigate the influence of sleep quality, OSA risk and total sleep time (TST) of prior night in level of activation of the frontal cortex using functional near‐infrared spectroscopyMethodWe investigated 204 participants without cognitive impairment between the ages of 60 and 85 years. All patients functional near‐infrared spectroscopy (fNIRS) along with cognitive tasks, including digit span, semantic verbal fluency task, stroop test, to investigate hemodynamic response in the fontal cortex of patients with depression compared to a healthy elderly group. The Pittsburgh Sleep Quality Index (PSQI) for sleep quality, STOP‐BANG questionnaire for risk of OSA, and TST of prior night which reported by participants was assessed.ResultIn poor sleep quality group (PSQI<5), reduced hemodynamics during the Stroop task compared to control group in all channel average (Mean accΔHbO2 of 0.11μM in poor sleep quality group versus ‐0.12 μM in control, p<0.05) and right channel average (Mean accΔHbO2 of 0.01μM and ‐0.03 μM, p<0.05). In sleep deprived group (TST<5), reduced hemodynamics during the verbal fluency test was observed in right channel average (Mean accΔHbO2 of 0.024 in sleep deprived group versus 0.01 μM in control, p<0.05). There was no significant difference between high risk of OSA group (STOP‐BANG>5) and control group in all cognitive tasks.ConclusionPoor sleep quality and sleep deprivation (<5 hours) may be an important factor that influences cortical oxygenation in the elderly population.
Potentially inappropriate medication use in people with dementia in China and its associated factors
Authors: Nguyen Tuan Anh , Du Duc , Dang Thu Ha , Wang Haipeng , Qiang Sun , Roughead Elizabeth E 
Published: December 2020

AbstractBackgroundMedicine use in people with dementia is challenging. This study was conducted to examine the use of potentially inappropriate medicines that may affect cognition (PIMcog) or reduce the effectiveness of cholinesterase inhibitors (CEIs) in people with dementia.MethodA cross‐sectional study of people with dementia admitted to hospitals in Shandong, China between 31st Dec 2014 and 31st Dec 2016 was conducted. Patients’ medical records were reviewed and their medicine use assessed. Polypharmacy was defined as use of five or more medicines in the same hospital episode. Concomitant use of CEIs with anticholinergic medicines was assessed using a list of medicines with clinically relevant anticholinergic property based on a consensus combination of different anticholinergic scales. Use of PIMcog was assessed against a list of PIMcog developed based on relevant Beers 2012 and STOPP 2014 criteria. Variables associated with having a PIMcog were assessed using a multiple logistic regression.ResultOf the 453 participants with a mean age of 75.9 years, 98.7% used polypharmacy, 56.1% used a PIMcog, 30.7% used CEIs concomitantly with anticholinergics, and 32.2% used antipsychotics. PIMcog use was associated with higher number of comorbidities (adjusted OR 1.14; 95% CI: 1.04 ‐ 1.33), higher number of other medicines prescribed rather than PIMcog (adjusted OR 1.07; 95% CI: 1.01 ‐ 1.13) and types of prescribers.ConclusionUse of polypharmacy and medicines that can further impair cognition or reduce the effectiveness of CEIs in people with dementia was prevalent. Efforts to improve quality use of medicines for this population are warranted.
Decreased JNK3 levels are associated with amyloid plaque and neurofibrillary tangles in dementia patients
Authors: Cheng Ai Ling , Chong Joyce R , Lee Jasinda , Attems Johannes , Aarsland Dag , Francis Paul T , Lai Mitchell Kim Peng 
Published: December 2020

AbstractBackgroundMany studies have provided strong evidence to support JNK3 isoform‐specific involvement in several processes underlying Alzheimer’s Disease (AD) pathogenesis including dysfunction of synaptic plasticity and cognition, phosphorylation of tau and amyloidogenic processing of the amyloid precursor protein. Moreover, the tissue‐specific expression of JNK3 primarily in the brain suggests a potential pivotal role of JNK3 in the central nervous system.MethodUsing immunoblotting, JNK3 levels were measured in the post‐mortem parietal lobe cortex (Brodmann Area 40) of a cohort of longitudinally assessed Alzheimer’s Disease (AD), Lewy Body Dementia (LBD), and healthy control patients. Although LBD brains are mainly characterized by the presence of α‐synuclein‐containing lewy bodies, It has been shown that LBD brains exhibit a substantial degree of AD pathologies, including amyloid plaques and neurofibrillary tangles particularly in cortex regions associated with higher cognitive functions. We investigated the association between levels of JNK3 and several neuropathological measures too.ResultWe found a significant decrease in JNK3 levels in all dementia groups compared to control. Our results also showed that levels of JNK3 were significantly associated with amyloid plaque (AP) and neurofibrillary tangle (NFT) pathology scores but not lewy body (LB) scores.ConclusionOur results suggest a possible compensatory mechanism to maintain levels of JNK3 to protect against further pathological damage. It was suggested that this compensatory effect is the brain’s adaptive means in response to pathological insults, to aid in dampening further damage during disease progression, and that these compensatory changes usually comes into play in the ‘latent’ phase of disease progression. In addition, JNK3 is likely to be involved in AD‐related processes but not in mechanisms that are associated with driving the formation of α‐synuclein pathological aggregates. The role of JNK3 in LBD could be in relation to common pathogenic pathways that underlie all dementia.